# Patent

## Title
Electrochemically mediated atom transfer radical polymerization

## Abstract

Electrochemical reduction of an exemplary ATRP catalyst, CIIBr2/Me6TREN, is shown to be an efficient process to mediate and execute an ATRP. The onset of polymerization occurs only through passage of a cathodic current achieved under a reductive potential to form CuIBr2/Me6TREN, within the reaction medium. Unprecedented control over the polymerization kinetics can be attained through electrochemical methods by modulating the magnitude of the applied potential allowing polymerization rate enhancement or retardation. Additional polymerization control is gained through electrochemical “dials” allowing polymerization rate enhancements achieved by larger applied potentials and the ability to successfully switch a polymerization “on” and “off between dormant and active states by application of multistep intermittent potentials.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a U.S. national stage filing under 35 U.S.C. §371 of International Application No. PCT/US2011/065578 having an international filing date of Dec. 16, 2011 and claims benefit of and priority to U.S. Provisional Application Ser. No. 61/574,890 filed Aug. 11, 2011, and U.S. Provisional Application Ser. No. 61/459,724 filed Dec. 17, 2010, the disclosures of each of which are incorporated by this reference.


TECHNICAL FIELD OF THE INVENTION
An atom or group transfer polymerization process where the ratio of the activator and deactivator oxidation states of the catalyst complex in the reaction medium is dictated and continuously balanced by electrochemistry. The rate of polymerization can be controlled through the magnitude of the applied potential, current, or total charge passed to the system. The polymerization can be switched “on” and “off” at will to control the temperature of the reaction medium.
BACKGROUND OF THE INVENTION
Since their discovery, controlled radical polymerization (CRP) processes have gained increasing attention because CRP couples the advantages afforded by conventional free radical polymerization (RP), to (co)polymerize a wide range of monomers using various commercially viable processes, with the ability to synthesize polymeric materials with predetermined molecular weight (MW), low polydispersity (Mw/Mn), controlled composition, site specific incorporated predetermined functionality, selected chain topology and the ability to incorporate bioresponsive or inorganic species into the final product.
Atom transfer radical polymerization (ATRP) is considered to be one of the most successful CRP processes with significant commercial potential for production of many specialty materials including coatings, sealants, adhesives, dispersants in addition to materials for health and beauty products, electronics and biomedical applications. The process, catalysts, including transition metals and ligands, range of polymerizable monomers and materials prepared by the process have been thoroughly described in a series of co-assigned U.S patents and Applications including U.S. Pat. Nos. 5,763,548; 5,807,937; 5,789,487; 5,945,491; 6,111,022; 6,121,371; 6,124,411; 6,162,882; 6,407,187; 6,512,060; 6,538,091; 6,541,580; 6,624,262; 6,624,263; 6,627,314; 6,759,491; 6,790,919; 6,887,962; 7,019,082; 7,049,373; 7,064,166; 7,125,938; 7,157,530; 7,332,550; 7,572,874; 7,678,869; 7,795,355; 7,825,199; 7,893,173; 7,893,174 and U.S. patent applications Ser. Nos. 10/548,354; 11/990,836; 12/311,673; 12/451,581; 12/921,296; 12/877,589; 12/949,466 and 13/026,919 the disclosures of all of which are herein incorporated by reference. These prior art patents and applications describe the range of (co)polymerizable monomers in addition to the topology, architecture and site specific functionality attainable in copolymers prepared by ATRP in addition to detailing a range of composite structures that can be prepared by “grafting from” or “grading to” a broad range of organic or inorganic materials.
ATRP has also been discussed in numerous publications with Matyjaszewski as co-author and reviewed in several book chapters. [Matyjaszewski, K. et al. ACS Symp. Ser. 1998, 685, 258-283; ACS Symp. Ser. 1998, 713, 96-112; ACS Symp. Ser. 2000, 729, 270-283; ACS Symp. Ser. 2000, 765, 52-71; ACS Symp. Ser. 2000, 768, 2-26; ACS Symposium Series 2003, 854, 2-9; ACS Symp. Ser. 2009, 1023, 3-13 and Chem. Rev. 2001, 101, 2921-2990.] These publications are incorporated by reference to provide information on the range of suitable transition metals that can participate in the redox reaction and suitable ligands for the different transition metals to form transition metal complexes suitable for polymerizing broad range of exemplified polymcrizable (co)monomers. The generally accepted mechanism of an ATRP reaction is shown in Scheme 1.




Any transition metal complex (Mtn/L) capable of maintaining the dynamic equilibrium through participation in a redox reaction comprising the transferable atom or group present on each initiator or dormant polymer chain (Pn—X) to form an active radical (Pn•) and higher oxidation state transition metal complex (X-Mtn+1/L) that acts as the deactivator, may be used as the catalyst in ATRP. The creation and maintenance of a low concentration of active species, (Pn•), reduces the probability of bimolecular termination reactions, (kl), which leads to a radical polymerization process that behaves as a “living” system through retention of the stable transferable atom or group (—X) on the vast majority of growing dormant chain ends. The most frequently used ATRP procedure is based on a simple reversible halogen atom transfer catalyzed by redox active transition metal compounds, most frequently copper or iron, that form a catalyst complex with a ligand that modifies solubility and activity of the catalyst, most frequently nitrogen based ligands. The simple procedure may be carried out in bulk, in the presence of organic solvents or in water, under homogeneous or heterogeneous conditions, in ionic liquids, and in supercritical CO2.
Early ATRP procedures required addition of a sufficiently high concentration of the transition metal complex to overcome the effect of unavoidable increased concentration of the deactivator in the reaction medium while still driving the reaction to the desired degree of polymerization in a reasonable time frame while retaining chain end functionality. Recently a novel approach that allowed a significant reduction in the concentration of added catalyst was developed. [PCT Int. Appl. WO 2005/087819; Camegie Mellon University, 2005; 96 pp.] The driving force was the economic penalty associated with purification procedures coupled with a deeper understanding of the ATRP rate law (Equation 1. using CuI as the catalyst metal) which shows that Rp, the polymerization rate, depends only on the ratio of the concentration of [CuI] to [X—CuII], and does NOT depend on the absolute concentration of the copper complexes (Equation 1). Therefore in principle, one could reduce the absolute amount of copper complex to ppm levels without affecting the polymerization rate.




  
    
      
        
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However, a balance had to be reached between the formed activator species (i.e. CuI/L, where L=ligand) and a residual amount of deactivating species (i.e. X—CuI/L) which is required for a well-controlled polymerization since both, molecular weight distribution and initial molecular weight, depend on the ratio of the propagation and deactivation rate constants and the concentration of deactivator, formula (2).




  
    
      
        
          
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This means, for example, that in order to obtain polystyrene with Mw/Mn= ̃1.2, when targeting a DP ̃200 and 90% conversion at  ̃100° C, the actual amount of X—CuII species required to conduct a controlled reaction is  ̃2 ppm (kp ̃103 M−1s−1 and kds ̃107 M−1s−1), meaning that the concentration of the X—CuII species could be reduced over 1,000 times from the level typically used in the earlier ATRP polymerization protocols. Unfortunately, if the amount of CuI is reduced 1,000 fold, unavoidable radical-radical termination reactions irreversibly consume the activators present in the reaction media as the polymerization progresses and the reaction slows down or stops; i.e. if  ̃10% of chains terminate and the amount of CuI initially added to the system was below 10 mole % of the initiator, all CuI would be consumed by termination. It was recognized that this situation could be overcome if there was constant regeneration of the CuI activator species by environmentally acceptable organic or inorganic reducing agents to compensate for any loss of CuI by termination, Scheme 2.




This procedure was named Activator ReGenerated by Electron Transfer (ARGET) ATRP [Macromnlecules 2006, 39, 39-45.] and it was possible to use a range of reducing agents; e.g. tinII-2-ethylhexanoate, ascorbic acid, glucose, amines, excess ligand, and Cu0 etc. for ARGET or a source of free radicals, such as AIBN, for Initiators for Continuous Activator Regeneration (ICAR) to constantly regenerate the ATRP activator, exemplified by a CuI species, from the deactivator, the CuII species in Scheme 2, formed during termination processes.
The electrochemical mediated ATRP procedure disclosed herein overcomes the limitations of ARGET and ICAR ATRP in that no undesirable byproducts are formed and a ratio of CuIL:CuIIL can be selected and retained or adjusted throughout the polymerization.
Cyclic voltammetry (CV) has been used for over a decade as an analytical tool to study the redox behavior of numerous transition metal complexes used in an ATRP. One of the earliest studies, [Qiu, J., et al., Macromol. Chem. Phys. 2000, 201, 1625-1631.] determined that the half-sum of the oxidation and reduction peak, the E1/2 value, strongly depends on the nature of the ligand and the halogen and the measured value provided an estimate for the activity of the catalyst complex (CuIL/CIIL redox couple) in an ATRP, and that this value strongly depends on the nature of the ligand (L) and the halogen. The general trend agreed with the kinetic features of ATRP catalyzed by the corresponding transition metal complex, and a correlation between the measured redox potential and the apparent equilibrium constant of ATRP was observed. The more negative the redox potential of the complex, as measured by CV, the faster the polymerization indicating that, in most cases, the catalytic activity of the transition metal complexes in an ATRP can be predicted from the redox potential of the transition metal complex. Two more recent studies by the primary author, K. Matyjaszewski, on a broader spectrum of transition metal/ligand complexes in a number of different solvents confirmed the conclusion that excellent correlation existed between the equilibrium constants with the CuII/CuI redox potential and the carbon-halogen bond dissociation energies. [Matyjaszewski; et al. Macromoleades 2007, 40, 8576-8585 and J. Am. Chem. Soc. 2008, 130, 10702-10713.]
This analytic tool, CV analysis, was used extensively to provide information on the expected properties of the transition metal complex in an ATRP. [Bortolamei, N., et al., Macromolecules, 2010: 43, 9257-67 and Electrochim. Acta, 2010, 55(27): 8312-8318.] CV analysis had always been carried out in the absence of monomer and in the absence of initiator. However, there is a recent paper, by one of the authors of the initial CV paper, (C. Amatore) where the notion of utilizing an electrochemical technique to produce an electrogenerated FeIISalen complex providing activation of alkyl- and benzyl halide initiators as the initial step of an atom transfer radical addition (ATRA) reaction. [J. Electroanal. Chem. 2009, 633, 99-105] CV's conducted in the absence and presence of an ATRP initiator showed that reductive cleavage of the R—X bond occurred on the timescale of the CV measurement but suggested that it does not lead to a classical redox-catalysis framework. Additionally, it was noted that addition of a monomer adversely affected the voltammogram of the studied iron complex. Attempts to polymerize styrene at 110° C., a temperature at which self initiated polymerization occurs, in the presence of a FeIISalen complex formed by electrolysis resulted in the formation of low molecular weight oligomers with broad polydispersity over a three hour period (MW 1868, Mw/Mn1.768). Furthermore, the paper indicates that multiple transition metal/ligand/initiator species were involved in the reaction and determined that activation of alkyl halides by an electrogenerated FeIISalen complex did not proceed along the redox mediated process usually invoked in an ATRP and the results presented showed no evidence of the development of a CRP process. These results would teach against using electrochemistry to improve the degree of control an ATRP.
In US2011/0034625A1 the concept of using electrochemically produced free radicals for the initiation of a standard free radical polymerization is considered. The procedure focuses on direct formation of free radicals, substantially hydroxyl radicals, on the basis of electrolysis at anodic electrode surfaces. While indicating that the procedure could be employed to initiate a CRP this reference provides no evidence of a methodology which would allow manipulation of a redox-active species via electrochemical methods to subsequently control a CRP procedure.
There are no reports in the decade since the first report using cyclic voltammetry as an analytical tool to measure the redox potential of a transition metal complex to determine if electrochemistry could be used to mediate an ATRP. The notion of utilizing an electrochemical technique (i.e. electrolysis) to modulate polymerization kinetics has never been reported.
BRIEF DESCRIPTION OF THE INVENTION
Disclosed herein in one embodiment of the invention is an atom or group transfer polymerization process where the ratio of the activator and deactivator oxidation states of the catalyst complex in the reaction medium is continuously balanced, adjusted, controlled, or dictated and maintained by electrochemistry.
According to one embodiment, the present disclosure provides for a polymerization process, comprising: polymerizing free radically (co)polymerizable monomers in the presence of a polymerization medium. The polymerization medium initially comprises at least one transition metal catalyst that can participate in a redox reaction, and an initiator comprising one or more redox transferable atoms or groups, wherein the molar ratio of the oxidation states of the transition metal catalyst are adjusted, controlled, and/or maintained by electrochemistry. The electrochemistry may include adjusting, controlling and/or maintaining one or more of an applied voltage, a current, and a charge passed through the polymerization medium.
In another embodiment of the invention his novel procedure was also applied to aqueous based ATRP, both homogenous and heterogeneous systems.



DESCRIPTION OF EMBODIMENTS OF THE INVENTION
The following figures illustrate that procedures were developed for controlled elcctrochemically mediated ATRP, (“eATRP”).
FIG. 1: Schematic of an electrochemical cell listing some of the electrical variables and electrolyte variables targeting an ATRP reaction with a copper catalyst.
FIG. 2: Schematic of electrolysis cell configured with a platinum mesh working and counter electrode used in certain eATRP experiments.
FIG. 3: Results of conducting cyclic voltammetry (CV) on (A) a solution of MeCN/MA solvent/monomer and (B) a solution of CuIIBr2 in MeCN/MA.
FIG. 4: Cyclic voltametry of a solution of MeCN/MA/Me6TREN/CuIIBr2, in the absence (black curve), and in the presence of EBP (grey curve), an ATRP initiator.
FIG. 5: GPC traces of polymers formed at different conversions during electrochemical mediated ATRP of MA with different applied voltages; (A)E=−0.637 and (B)E=−0.665 V
FIG. 6: Illustration of how the polymerization of methyl acrylate can be “switched on” and “switched off” by changing the E(V) between two electrodes.
FIG. 7: Increase in molecular weight and change in Mw/Mn with conversion during the intermittent polymerization illustrated in FIG. 6.
FIG. 8: Total charged (Q) and current (I) as a function of time, Exp. 2−E=−0.637
FIG. 9: Cyclic voltammetry of CuIIBr2/TPMA and various initiators. In each system the [M]=4.67 M and [TBAPF6]=0.2 M. Molar ratios=[M]:[I]:[CuIIBR2/L]=300:1:0.2.
FIG. 10: Cyclic voltammetry of 1 mM CuIIMe6TREN in the absence and presence of different [MBrP], recorded at v=0.05 V/s on Pt, in AN/MA 1:1+0.1 M Et4NBF4.
FIG. 11: Cyclic voltammetry of 1 m M CuIIMe6TREN in the absence (a) and presence (b) of 1 mM Et4NBr, recorded at v=0.05 V/s on Pt, in 0.1 M Et4NBF4+0.1 M Et4NBF4.
FIG. 12: cyclic voltammetry of CuIIBr/TPMA and ferrocene.
FIG. 13: Current versus time and cyclic voltammetry conducted periodically during polymerization. Polymerization conditions: [MMA]=4.5 M, [MMA]:[EBPA]:[TPMA]:[CuII]=300:1:0.1:0.1, T=50° C.
FIG. 14: Position of E1/23, E1/2 and E1/4 applied potentials in optimization series of experiments for MMA showing the exemplary CV of the CuI/CuII couple.
FIG. 15: (A) Current profile for polymerization of MMA using EBPA showing occurrence of tdrop after a certain amount of time, exemplary for reaction 16.4. (B) Comparative current profile for polymerization of BA with EBiB initiator under similar conditions.
FIG. 16: (A) Cyclic voltammetry of CuIITrf/L (black), CuIIBr/L (gray), and CuIIBr/L with EBiB (dashed) and (B) Current and Coulombs versus time plot.
[BA]/[EBiB]/[TPMA]/[CuIITrf2]/[TPMA]/[TBABr]=300/1/0.03/0.03/0.03, [BA]=3.87 M (43 (v/v) % in DMSO:Anisole), [TBAClO4]0.2 M, T=40-45° C.
FIG. 17: (A) Cyclic voltammetry of CuIIBr/L (black), CuIIBr/L+EBiB (dash), and CuIIRr/L+EBiB+convection (gray). (B) First order kinetics versus time plot as a function of Eapp.
FIG. 18: (A) Cyclic voltammetry of PnBA-Br macroinitiator. (B) Plot of mmol electrolyzed (N) and current (I) versus time. Starting conditions: [PnBA]=0.02 M, [PnBA]:[DVB]:[TPMA]:[CuII]1:12:0.2:0.1, T=90° C.
FIG. 19. CV of 1 mM CuIIL2+ in H2O/OEOMA475 (9/1, v/v)+0.1M Et4NBF4 recorded at v =0.1 V/s in the absence ( - - - ) and presence (black solid) of 1 mM HEBriB; the three dots on the CV indicate the Eapp values used in the polymerization experiments.
FIG. 20: Cyclic voltammetry of 1 mM CuIIL2+ in the absence (a) and presence of 1 mM HEBriB (b) or 2 mM HEBriB (c), recorded at 0.1 V/s in H2O+0.1 M Et4NBF4.
FIG. 21. First-order kinetic plots for electrochemical ATRP of OEOMA475 in H2O+0.1 M Et4BF4 at Eapp=−0.21 V vs SCE. Conditions: [CuIIL2+]=0.1 mM; [OEOMA]/[RX]=1000 (●), 500 (▾), 200 (▴).
FIG. 22. CV of miniemulsions at a range of scan rates of CuII/BPMODA and after the addition of CuII/TPMA at 0.5 V/s.
FIG. 23: CV of miniemulsions (A) formulated without CuII/BPMODA or EBiB, and (B) with and without copper for TPMA. CVs conducted at a scan rate of 0.05 V/s using a glassy carbon electrode.
FIG. 24: (A) Current versus time profile for electrolysis (Eapp=Ep−80 mV) and (B) Potential versus time at two Iapps.
FIG. 25: (A) First order kinetics versus time plot as a function of an applied E or I and (B) Molecular weight and Mw/Ma versus time plot for eATRP of B A in DMF.
FIG. 26: Cyclic voltammetry of CuIIBr/TPMA.
FIG. 27: (A) Conversion versus time plot as a function of applied potential. (B) Molecular weight and Mw/Mn versus time plot for eATRP of BA in DMF.



DETAILED DESCRIPTION
The present disclosure provides for a new radical polymerization process, such as a controlled radical polymerization process. The polymerization process described herein may includes polymerizing free radically (co)polymerizable monomers in the presence of a polymerization medium initially comprising at least one transition metal catalyst that can participate in a redox reaction, and an initiator comprising one or more redox transferable atoms or groups, wherein the molar ratio of the oxidation states of the transition metal catalyst are adjusted, controlled, and/or maintained by electrochemistry. Examples of polymerization processes that are suited to the present process include, for example, atom transfer radical polymerization processes.
Here, and elsewhere in the text the word “control” and/or “controlled”, when used in reference to a “controlled” polymerization process means that in the polymerization process conditions are defined whereby the contributions of the chain breaking processes are insignificant compared to chain propagation, so that polymers with predetermined molecular weights, low polydispersity and high site specific functionalities are achievable. Examples of a controlled polymerization processes described herein include controlled radical polymerization (CRP) processes, such as atom or group transfer radical polymerization (ATRP) processes.
As used herein, “polymer” refers to a macromolecule formed by the chemical union of monomers, typically five or more monomers units. The term polymer includes homopolymers and copolymers; including random copolymers, statistical copolymers, alternating copolymers, gradient copolymers, periodic copolymers, telechelic polymers and polymers of any topology including linear polymers, block copolymers, graft polymers, star polymers, bottle-brush copolymers, comb polymers, branched or hyperbranched polymers, and such polymers tethered to particle surfaces or flat surfaces as well as other natural or synthetic polymer structures.
It must be noted that, as used in this specification and the appended claims, the singular forms “a,” “and”, and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a polymer” includes more than one polymer.
Unless otherwise indicated, all numbers expressing quantities of ingredients, time, temperatures, and so forth used in the present specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, may inherently contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
It is to be understood that this invention is not limited to specific compositions, components or process steps disclosed herein, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. Any patent, publication, or other disclosure material identified herein is incorporated by reference into this specification in its entirety unless otherwise indicated, but only to the extent that the incorporated material does not conflict with existing definitions, statements, or other disclosure material expressly set forth in this specification. As such, and to the extent necessary, the express disclosure as set forth in this specification supersedes any conflicting material incorporated by reference herein. Any material, or portion thereof, that is said to be incorporated by reference into this specification, but which conflicts with existing definitions, statements, or other disclosure material set forth herein, is only incorporated to the extent that no conflict arises between that incorporated material and the existing disclosure material. Applicant reserves the right to amend this specification to expressly recite any subject matter, or portion thereof, incorporated by reference herein.
According to one embodiment, the present disclosure provides a polymerization process comprising polymerizing free radically (co)polymerizablc monomers in the presence of a polymerization medium initially comprising at least one transition metal catalyst that can participate in a redox reaction and an initiator comprising one or more redox transferable atoms or groups, wherein the molar ratio of the oxidation states of the transition metal catalyst are adjusted, controlled and/or maintained by electrochemistry, such as by applying or changing one or more of an applied voltage, a current, and a charge passed through the polymerization system. Examples of polymerization processes include controlled radical polymerization processes, such as atom transfer radical polymerization (ATRP) processes. General conditions and components for ATRP processes and other controlled radical polymerization processes are known in the art, as shown by the references cited and incorporated by reference herein. For example, examples of transition metal catalysts, radically (co)polymerizable monomers, and initiators comprising one or more redox transferable atoms or groups are described in detail in the references cited and incorporated herein. Suitable transition metal catalysts include transition metals and complexes of transition metals with various ligands, including those transition metal catalyst complexes and ligands shown to be effective in the art for ATRP processes. In certain embodiments, the transition metal catalyst may comprise two different transition metals.
Embodiments of the controlled polymerization processes described herein may be designed so that the polymerization may take place in an electrolysis apparatus comprising at least a cathode and an anode. Non-limiting examples of electrolysis apparatuses are shown in FIGS. 1 and 2. According to these embodiments, the polymerization process may be controlled by the electrolysis apparatus, for example, by applying or changing one or more of an applied voltage, a current, and a charge passed through the polymerization medium. The electrolysis or electrochemical process may be selected so to control or maintain the ratio of the oxidation states of the transition metal catalyst, such as by providing a concentration for each oxidation state of the transition metal catalyst that is greater than or equal to 0.1% based on the total transition metal added in the polymerization medium.
In specific embodiments, the molar ratio of two oxidation states of the transition metal catalyst at a specific time during the polymerization process may be determined by one or more of the applied voltage, the current, and the total charge passed through the polymerization medium and the current values. For example, in a copper transition metal catalyst based system, the electrolysis may be selected to maintain the concentration of the CuI and/or CuII oxidation states of the transition metal catalyst at greater than or equal to 0.1% by weight based on the total concentration of Cu added to the polymerization medium. According to these embodiments, the rate of the polymerization may be controlled through the magnitude of one or more of the applied voltage, current and charged passed that is applied to the system.
Initial examples of the disclosed electrochemically mediated ATRP (eATRP) process employ a single catalyst complex, Cu/Me6TREN, which is used as an exemplary active transition metal catalyst system in the following discussion but this in no manner limits the utility of the disclosed procedure to the exemplary catalyst. Any transition metal catalyst or transition metal catalyst complex that has been shown, or will be shown, to control an ATRP can be used in the disclosed procedure.
The specific materials selected for the preparation of electrodes used in this disclosure are exemplary materials and should not limit the choice of electrode materials in any manner nor the materials or design of the cell for either batch or continuous electrochemical mediation of the polymerization. One requirement of the disclosed eATRP procedure is that the selected current/potential is applied to a reaction medium that contains all, or precursors of all, reagents required for the polymerization and maintained for a time frame which exceeds a standard CV analysis of a potential ATRP catalyst complex. Appropriate current/potential values can be selected based upon the standard redox couple (E1/2) determined for the reaction medium including catalyst, monomer and optional solvent in the presence or absence of an initiator. Procedures for selection of an appropriate reduction potential for each desired (co)polymerization reaction with a specific catalyst complex in a specific reaction medium are discussed below. The E1/2 redox couple for the polymerization medium may be determined by any suitable means, for example, by cyclic voltammetry (CV). If an appropriate charge is selected for a catalyst complex and (co)monomer(s) as disclosed herein, rather surprisingly, electrochemical procedures can provide a method for forming a targeted fraction of the activator species from an added deactivator resulting in initiation of the ATRP by transfer of the transferable atom or group from the added initiator to the formed lower oxidation state transition metal complex thereby initiating controlled copolymerization of a wide range of monomers generating copolymers with low Mw/Mn and high degrees of polymerization.
In certain embodiments, the voltage applied to the polymerization medium may be based on the E1/2 value, as determined for example by CV. The voltage applied to the polymerization medium may be determined by the components in the polymerization. For example, in one embodiment, the voltage applied to the polymerization medium may be based on the E1/2 value, as determined by CV, of the at least one transition metal catalyst and the one or more ligands present in the polymerization medium. In another embodiment, the voltage applied to the polymerization medium may be based on the E1/2 value, as determined by CV, of the at least one transition metal catalyst, the one or more ligands, and the radically (co)polymerizable monomers present in the polymerization medium and optionally any solvent and/or any electrolyte present in the polymerization medium. In other embodiments, the voltage applied to the polymerization medium may be based on the E1/2 value, as determined by CV, of the at least one transition metal catalyst, one or more ligands, the radically (co)polymerizable monomers, and the initiator comprising one or more redox transferable atoms or groups, present in the polymerization medium and optionally any solvent and/or any electrolyte present in the polymerization medium.
The overall mechanism of an electrochemically mediated ATRP is shown in Scheme 3.




The influence of the applied potential, the electrodic area, the concentration profile of CuI and CuII during the electro-mediated polymerization, and the solvent-monomer ratio on the crucial features of an ATRP including conversion, polymerization time, molecular weight and polydispcrsity were studied and are reported below. Analysis of these parameters together with the charge-current patterns can provide a deep comprehension of the dynamics of the system, and in particular an understanding of how the heterogeneous electrochemical process affects the homogeneous or biphasic polymerization procedure.
In various embodiments, the concentration of the transition metal catalyst in the polymerization medium may be less than 1000 ppm, or in other embodiments less than 500 ppm. For example, starting from a low amount (<1000 ppm, preferably less than 500 ppm) of deactivator (X—CuII/L), the activator (CuI/L) may be generated in-situ by electrolysis at a carefully selected reduction potential. When generated, the activator molecules can then react with the redox transferable atom or group, for example, the carbon halogen bond, of the initiator molecules or dormant chain end, Pn—Br in scheme 3, forming active radicals through the traditional ATRP mechanism. These radicals can propagate with monomer prior to being returned to the dormant alkyl halide form by reacting with a deactivator molecule (X—CuII/L), or terminate with other radicals with a rate constant of kt. In this system, activator molecules are continuously regenerated at the working electrode (i.e. cathode) to maintain a selected ratio of activator to deactivator and hence control the rate of polymerization. In this manner a constant ratio of activator to deactivator can be maintained in the polymerization medium thereby continuously maintaining the targeted rate of polymerization.
According to certain embodiments, the polymerization process can be started and stopped by changing the applied voltage or current, or switching the applied voltage or current “on” or “off”. For example, changing the applied voltage or current or switching the applied voltage or current on or off, the system may provide a simple means to control any reaction exotherm. Indeed, in certain embodiments the reaction temperature may be used as a control to modify and adjust the timeframe, magnitude and voltage of the applied current to maintain the desired reaction rate at a controlled temperature as the reaction progresses. This allows unprecedented control over the polymerization procedure. Mechanical mixing of the reagents in the reaction flask assists in forming a homogeneous reaction medium by providing efficient mass transport of the generated catalyst complex away from the working electrode.
As disclosed herein electrochemical methods provide significant improvements to, and control over, an ATRP by offering readily adjustable “dials”, e.g. applied voltage, current, potential, and total charge passed, to manipulate polymerization activation/deactivation, polymerization rates, and selective targeting of one or more redox-active species. In addition, electrochemistry offers an environmentally friendly alternative to current ATRP techniques that use comparable low concentrations of catalyst complex by elimination of chemical agents to form the activator and a new approach to catalyst removal through electrodeposilion.
In one embodiment of the invention the ratio of the two oxidation states of the catalyst complex in an atom or group transfer polymerization process is monitored and balanced by electrochemistry, for example, continuously monitored and/or continuously balanced, thereby dictating the rate of polymerization without formation of any by-products. For example, according to various embodiments, the electrochemistry selected from applied potential, current, and charged passed may be adjusted one or more times during the polymerization process. In specific embodiments, the electrochemistry may be continuously monitored and adjusted over the course of the polymerization reaction.
In specific embodiments, the polymerization medium may further comprise one or more electrolytes. Suitable electrolytes include any ionic compound that is at least partially soluble in an aqueous phase of the polymerization medium. Non-limiting examples of electrolytes include those listed in US 2011/0034625 A1. In certain embodiments, the electrolyte may comprise the same counterion that is present on the first added transition metal salt that forms the at least one transition metal catalyst. For example, in embodiments where CuIIBr2 is added as the transition metal salt which will form the transition metal catalyst, the electrolyte may also comprise a Br−counterion. In other embodiments, the electrolyte may comprise a different counterion than the anion present on the first added transition metal salt that forms the at least one transition metal catalyst. For example, in embodiments where CuIIBr2 is added as the transition metal salt which will form the transition metal catalyst, the electrolyte may comprise an OTf− (triflate or trifluoromethanesulfonate) counterion. In certain embodiments, the electrolyte may comprise a quaternary ammonium complex or a triflate anion. In specific embodiments where the polymerization medium further comprises an electrolyte, the electrochemistry may be selected from an applied voltage and a current, and may be selected to retain at least 0.1% by weight concentration (based on total transition metal present) of an activator state of the transition metal catalyst and a deactivator state of the transition metal catalyst in the polymerization medium throughout the time period(s) when an active polymerization is desired.
Additional embodiments of the procedures are disclosed that allow a well controlled ATRP to be conducted with low concentrations of catalyst, very low concentrations of activator in a full range of solvents, including organic solvents, water, and biphasic systems.
The disclosed procedure allows one to dictate the concentration of both the activator and the deactivator in the reaction medium by adjusting the electronic potential of the current, or rate of flow of the charge. Indeed the electronic potential can, indeed should, be adjusted to match the catalyst system selected for the polymerization while providing optimal control over the radical polymerization of selected (co)monomers. The system provides additional control over the polymerization process by monitoring; total charged passed (Q) and current (I) values. Another method consists of placing a constant current (galvanostatic method) upon the electrochemical system and if desired measuring the variation of the voltage supplied at the working electrode.
According to certain embodiments, the transition metal catalyst may be a transition metal catalyst complex and comprise one or more ligands, and in specific embodiments may comprise two different ligands. Ligands may be used for a variety of reasons, for example, but not limited to, adjusting the solubility of the transition metal catalyst in the polymerization medium, or to control the reactivity of the transition metal catalyst. Suitable ligands for ATRP polymerization processes are known in the art and described in detail in the references incorporated herein. In specific embodiments, the ligands may include nitrogen containing ligands such as, but not limited to bipyridyl(bipy) based ligands, substituted pyridines (such as TPMA), and polyamines (such as Me6TREN), and the like.
In certain embodiments, the relative concentration of a higher oxidation state transition metal catalyst and a lower oxidation state transition metal catalyst may be adjusted through the magnitude of the voltage or current applied to the system, thus controlling the polymerization of the radically (co)polymerizable monomers with the at least one transition metal catalyst and the one or more ligands. For example, the relative activity of a catalyst complex formed with selected ligand(s) can be adjusted, i.e. the ratio of Mtx/L to Mtx+1/L, to provide control over the polymerization of a range of monomers just by changing the applied voltage. The rate of the polymerization is controlled by the selected ratio of Mtn to X—Mtn+1 with the rate increasing as the value of Mtn/X—Mtn+1 increases. More active catalysts require less activator in the system when polymerizing active monomers. Indeed as exemplified in the experimental section this is a novel tool that expands the range of monomers that can be polymerized in an expanded range of solvents including water.
If desired, the transition metal catalyst can be removed from the contacting polymer solution by electro deposition, leaving the added ligand(s) in solution. For example, the concentration of the transition metal catalyst in the polymerization medium may be reduced by electrodeposition of the transition metal onto the surface of one of the electrodes. The solvent/ligand/unreacted monomer mixture can be removed from the polymer and recycled whereupon the ligand can react with the first deposited transition metal, optionally in the presence of a halogen containing electrolyte and in the absence of an initiator to reform a soluble transition metal complex suitable for a further electrochemically mediated ATRP of additional mcnomer(s) after addition of an initiator. In other embodiments, the transition metal catalyst or transition metal catalyst complex may be formed in-situ directly from electrolysis of the solid transition metal deposited on an electrode. In one embodiment, a transition metal catalyst complex may be formed in-situ directly from a reaction of a solid transition metal deposited on an electrode with one or more ligands in the polymerization medium.
Therefore another embodiment of the invention comprises electrodeposition of a transition metal and reformation of a soluble transition metal complex by subsequent reverse reaction with a contacting ligand in the presence of a (pseudo)halogen electrolyte. This embodiment can also be employed in “normal” ATRP reactions for catalyst removal and recycling expensive ligands.
As shown in Scheme 3 a controlled predetermined fraction of an air stable CuIIBr2/Me6TREN catalyst complex initially formulated in, or added to, the polymerization media can be “at will” electrochemically reduced to CuIBr/Me6TREN by application of a selected cathodic potential to invoke a controlled polymerization, whereby the formed activators (i.e. CuIBr/Me6TREN) then react with an ATRP initiator molecule exemplified herein by an alkyl halide, further exemplified herein by a molecule with a transferable bromine, forming the corresponding deactivator (i.e. CuIIBr2/Me6TREN) and radicals capable of monomer addition in a reversible fashion. This dynamic equilibrium mediates the polymerization allowing concurrent growth of polymeric species resulted in a control polymerization and polymers with predetermined molecular weights and low Mw/Mn. Therefore, electrochemical activation of ATRP provides significant improvements to this polymerization procedure by offering additional tools for polymerization control and an environmentally friendly alternative to the chemical reduction of CuII to CuI.
The objectives initially targeted, and subsequently met, to exemplify this novel procedure include, but are not are not limited to, the following bullet points:

    
    
        Provide an understanding of the influence of each of the components of the electrolyte on an ATRP.
        Demonstrate polymerization control with specifically selected applied potential, or current, with alkyl (meth)acrylate(s) as exemplary monomers;
        Demonstrate that the ratio of CuI to CuII copper salts forming partially soluble catalyst complexes with active ligands, e.g. Me6TREN or TPMA, can be adjusted to control polymerization of a broad range of radically polymerizable monomers. This concept is based on the idea that the applied constant electric current can control the relative concentrations of CuI and CuII in the reaction medium and hence the kinetics, or instantaneous rate of the polymerization reaction for a range of monomers.
        Demonstrate preparation of macromolecules with complex topology.
        Develop an aqueous electrochemical system this is desired since:
        
            The vast majority of electrochemistry is conducted in aqueous media.
            Bio-responsive molecules are water soluble but can undergo undesired conformational changes in the presence of organic media.
        
        
        Identify a mixed catalyst complex for bi-phasic ATRP.
        Demonstrate catalyst removal by electrodepositing copper
    
    


Various embodiments of the polymerizations described herein may include a polymerization medium where the medium is selected from the group consisting of an organic medium, an aqueous medium, and a biphasic medium. Controlled/living/radical polymerizations (C/LRPs) described herein performed in aqueous media are very attractive both from economic and environmental points of view. In addition to the synthesis of water soluble polymers from polar monomers using the processes described herein, aqueous media can be used for the polymerization of nonpolar monomers in biphasic systems, for example, through emulsion, microemulsion, or miniemulsion techniques.
In one embodiment a mixture of reagents/ligands is employed in order to adapt emulsion systems to the eATRP process. Significant reaction modifications and mechanistic considerations must be taken into account in order to conduct a successful “triphasic” controlled polymerization. In a non-limiting exemplary formulation of an eATRP miniemulsion comprising an oil soluble BPMODA based catalyst system requires the addition of a second more hydrophilic catalytic complex (CuII/TPMA), reduced reaction temperatures (65° C), and addition of a supporting electrolyte (TEABF4) to efficiently activate the relatively isolated oil soluble dispersed BPMODA catalyst complex. Mechanistically, addition of a second copper ligand complex creates various pathways through which electrochemical activation of the dispersed catalyst could occur and overcomes the dual heterogeneous nature of the system comprising an oil/water and an electrode/water interface. The hydrophilic catalyst complex and/or bromine anions serve as electron messengers transporting electrons from the electrode to the organic phase by reacting with the more water soluble CuII ligand complexes) and initiator/dormant chain end(s) at, or close to, the phase boundary. The dual ligand communication pathway between an electrode and the dispersed organic phase operates in all stable biphasic polymerization media including microemulsion, miniemulsion and the ab initio emulsion system. Inverse emulsion systems could be controlled in a similar manner with an oil-soluble catalyst complex acting to shuttle the charge from the electrode to the dispersed aqueous phase.
In contrast to the remarkable success of ATRP in organic solvents, aqueous ATRP has been found to suffer from some limitations, especially in control and targeted degree of polymerization (DP). [J. Polym. Sci, Part A: Polym. Chem. 1998, 36, 1417-1427] Aqueous ATRP is usually fast with relatively high KATRP. [Chem. Rev. 2007, 107, 2270-2299] In addition, the halidophilicity (Kx) of CuIIL2+, i.e. association of X− to CuIIL2+ is low and the deactivator XCuIIL+ is not always stable toward dissociation. [Macromolecules 2004, 37, 9768-9778] Furthermore, certain CuIL+ complexes are unstable in water and may undergo disproportionation. In fact, control over an aqueous polymerization was improved by using high [X−], which helps to suppress deactivator dissociation. Developing successful aqueous ATRP requires taking all these issues into consideration. These limitations are overcome in an eATRP.
In a copper mediated aqueous eATRP the reaction mixture initially contains monomer, initiator, and CuIIL2+ (or CuIIL2++X—CuIIL+). No polymerization occurs under these conditions, as there is no CuIL+ activator in solution. The reaction starts only when a potential (Eapp) is applied to the cathode so that reduction of CuIIL2+ to CuIL+ occurs at the electrode. The value of Eapp can be appropriately chosen to achieve a continuous production of a small quantity of CuIL+ and consequently control the concentration of R• throughout the reaction. The livingness of the polymerization process is ensured by the combination of low [R•] and very high [CuIIL2+]/[CuIL+]. The overall rate of the process and the degree of control over polymerization can be tuned by adjusting Eapp.
One embodiment of the invention describes an electrochemical ATRP water based polymerization process by setting the Eapp to provide a combination of low [R•] and high [CuIIL2+]/[CuIL+] ratio, as high as 99.9/0.1. Indeed the overall rate of the process and the degree of control over the polymerization can be tuned by adjusting the Eapp.
Although development of AGET (Activators Generated by Electron Transfer) ATRP gives good results in terms of both control and DP, the appropriate ratio [CuII]/[reducing agent] and the nature of the reducing agent is critical. [J. Polym. Sci. Part. A. Polym. Chem. 2009, 47, 1771-1781]The ideal process should have a constant, high CuII/CuI ratio, which can hardly be achieved by a single addition of reducing agents. This limitation can be overcome in an eATRP as no added agents are required. In another embodiment targeting environmentally benign systems the concentration of transition metal in the polymerization medium is less than 1000 ppm, preferably less than 500 ppm and more preferably less than 100 ppm.
In another embodiment of the invention directed at preparing block copolymers with a single catalyst complex the degree of polymerization and dispersity of each block can be tuned by adjusting Eapp to attain optimal control over each block. After the first monomer is converted to a first segment the second monomer can be added and the Eapp adjusted to provide the desired level of control for the polymerization of the second segment(s) without changing the catalyst. Optionally if a “clean” second block, i.e. without incorporation of any residual “first” comonomers, is desired the current can be switched “off” and first comonomers removed leaving the catalyst complex present in the pure first block macroinitiator prior to adding the second comonomers then switching the second polymerization “on” by selecting the desired Eapp.
Various features of the present invention will become more apparent upon consideration of the following examples. The various embodiments of this disclosure described in the following examples are not to be considered as limiting the invention to their details. All parts and percentages in the examples, as well as throughout this specification, are by weight unless otherwise indicated.
EXAMPLES AND DISCUSSION OF EXAMPLES
The IUPAC definition of terms used in electrochemical reactions arc summarized in Chapter 1 of the Handbook of Electrochemistry, Edited by C. G. Zoski; Elsevier, 2007, and will be employed in the following discussion. This Handbook of Electrochemistry also provides information on selection of electrodes for the disclosed process. The electrodes used in the initial examples are chosen as exemplary materials and do not limit the choice of electrode materials in any manner. Definitions of terms, equations and important relationships are also provided in Electrochemical Methods, Fundamentals and Applications, A. J. Bard, L. R. Faulkner, second edition John Wiley & Sons, 2001. Chapter 11 of the book also provides a discussion on bulk electrolysis methods.










Abbreviations


















Tris((2-dimethylamino)ethyl)amine)
ME6TREN



Tris 2-pyridylmethylamine
TPMA



Bis(2-pyridylmethyl)octadecylamine
BPMODA



Ethyl α-bromophenylacetate
EBPA



Ethyl α-bromoisobutyrate
EBiB



Ethyl 2-bromopropionate
EBP



Hexadecane
HD



Methyl bromopropionate
MBrP



Tetrabutylammonium hexafluorophosphate
TBAPF6



Tetrabutylammonium bromide
TBABr



Tetrabutylammonium perchlorate
TBAClO4



Tetraethylammonium tetrafluoroborate
Et4NBF4



Tetraethylammonium bromide
Et4NBr



2-hydroxyethyl 2-bromoisobutyrate
HEBriB



Acetonitrile
MeCN



Dimethylsulfoxide
DMSO



Poly(ethylene glycol) methyl ether methacrylate
OEOMA475



Ethylene glycol diacrylate
EGDA



2-hydroxyethyl acrylate
HEA










In order to determine if the concept of utilizing electrochemistry to control an ATRP, summarized in Scheme 3, was indeed possible an electrochemical cell was constructed. The desired functions of the cell are represented in FIG. 1. It was envisioned, and then confirmed that, as shown in Scheme 3, the ATRP equilibrium could be controlled by subjecting the reaction medium to a specifically selected applied voltage, (Eapp). The exemplary electrochemical cell was designed to be suitable for both electrolysis of CuII and to provide control over a standard ATRP. A pear shaped five neck jacketed flask was selected as the foundation for a laboratory electrochemical cell and was equipped with a “rare earth” stirring element, a N2 purge, and a peristaltic pump for cooling. Each of the necks was fitted with either: a silver/silver (Ag/Ag+) ion reference electrode, a platinum mesh/disk working electrode, a platinum mesh counter electrode, and an inlet/outlet port for samples and reagents. A silver/silver reference electrode, a Pleskov electrode, was selected as reference electrode because it is well suited for electrochemistry in organic media; specifically the initial examples conducted with MeCN as solvent. The counter electrode was designed to be enclosed in a separate fritted compartment to reduce diffusion of oxidized species at the counter electrode into the polymerization occurring in the main compartment of the reactor. Therefore, the counter electrode was jacketed within a fritted compartment. The working electrode was made of a platinum mesh. A mesh was selected over a disk/button working electrode because of its larger relative surface area, although a platinum button working electrode was used for all analytical cyclic voltammetry (CV) measurements conducted prior to the addition of an initiator. Fabrication of all electrodes was undertaken within the laboratory, since they are not commercially available, and comprise a standard conductive wire encased in a glass compartment. The wire was soldered to platinum wire and coated with a chemically stable epoxy coating. A schematic of the reaction flask is shown in FIG. 2.
As exemplified in the following examples application of electrochemical techniques to ATRP introduces a unique and novel strategy to dynamically control this redox driven polymerization process. The initial experiments demonstrated that any desired fraction of the catalyst complex in an ATRP reaction medium formulated with air stable CuIIBr2/Me6TREN catalyst complex can be “on demand” reduced to provide targeted levels of CuIIBr/Me6TREN activators to invoke or trigger polymerization. The extent and rate of reduction is dictated by the initially applied potential (Eapp) allowing one to control the efficiency and rate of initiation from the added (pseudo)alkyl halide initiator. The ratio of CuIBr/Me6TREN:CuIIBr2/Me6TREN can be adjusted throughout the polymerization reaction to provide optimum control when taking into account the gradual increase in viscosity as the polymer chain increases in molecular weight and, with certain monomers, the change in polarity of the reaction medium as the reaction progresses. Further to this point, electrochemical methods allow lower oxidation state catalyst (CuIBr/Me6TREN) to be reverted back to their original higher oxidation state under an anodic potential providing a means to continuously balance the ratio of lower to higher states of the transition metal complex and if desired deactivate an ongoing polymerization.
Therefore in one embodiment of the invention alterations of polymerization rates through switching, or continuous adjusting of the catalyst oxidation states, allows enhanced levels of polymerization control and in essence enables precise modification of macromolccular species at any specified time during the polymerization.
Example 1
Influence of an Added Electrolyte on Polymerization of Methyl Acrylate
A series of control experiments were conducted focusing on understanding the influence of addition of an electrolyte to an ATRP. It is envisioned that any salt will suffice as long as it is soluble in the reaction medium. A variety of different acids and bases can be employed, indeed any molecule which is composed of ions or compounds which can be made into ions, including ionic liquids, are potential electrolytes. TBAPF6 was selected as an exemplary electrolyte due to its stability at a wide range of electrolytic potentials in MeCN. Two polymerizations were conducted utilizing copper wire as a reducing agent, one without and one with an electrolyte. The results are reported in Table 1. The system without an added electrolyte, entry 1, proceeded rapidly achieving a final conversion of 88% in 3 hours while maintaining linear first order kinetics and a strong correlation between experimental and theoretical molecular weights. Addition of TBAPF6 to the polymerization system resulted in slightly improved control, entry 2. First order kinetic behavior was observed, indicating the maintenance of a constant concentration of radicals throughout the polymerization, and molecular weights values clearly matched those of the theoretical values while attaining a narrow molecular weight distribution. These results confirmed that the addition of an electrolyte, with bulky non-coordinating counter ions has little, or no, adverse effects on an ATRP. This procedure of adding an electrolyte also provides a means to control the concentration of a desired counterion in the reaction medium.
Interestingly, switching the electrolyte anion from PF6− to bromide (Table 1, entries 2 and 3) changed the behavior of the system and a lower than targeted MW was obtained, entry 3, indicating lower initiation efficiency due to early termination reactions but a subsequent controlled polymerization. Upon increasing the concentration of the TBABr electrolyte, entry 4, lower final conversions and slower polymerization rates occurred. This behavior may be explained due to the fact that in a standard ATRP excess bromide ions are capable of displacing the Me6TREN ligand in the active transition metal complex, in agreement with the conclusions in a speciation paper by Bortolamei et al. [Macromolecules, 2010 9257].
Example 2
Electrochemically Mediated Polymerization of Butyl Acrylate (BA)
An initial scouting experiment was performed with butyl acrylate as monomer at the selected E1/2. The potentiometric charge was selected to provide a target conversion of 90% in 4 hours (14,400 seconds). The initial reaction conditions were: [M]0=5.56 M, [R—X]=0.0278 M, [CuIIBr2]=0.00139 M based on the knowledge that kp for methyl acrylate at 30° C.=16,600 M−1s−1 and KATRP for Cu/Me6TREN at 22° C. with MeBrP as initiator=2.9 E−6. It was calculated that the concentration of radicals in the system should be 9.622×E−9 which would require E0=E1/2=0.30 V to generate the required catalyst ratio of CuIBr/CuIIBr2= ̃0.12. Results of this experiment are reported in Table 2.







TABLE 1







Control polymerizations to determine influence of electrolyte on ATRP

















Exp.
ATRP System

[Electro]
[Cu0]
time
conv.b
Mn, theo
Mn, GPC




(#)
[MA]:[EBP]:[Me6TREN]:[CuIIBr2]
Electrolyte
(M)
(mm2/mL)/(mm)
(h)
(%)
(g/mole)
(g/mole)
Mw/Mn
Ieff




















1
500:1:0.05:0.05
None
0
40/53
3.0
88.4
38,174
32241
1.11
1.18


2
500:1:0.05:0.05
TBAPF6
0.11
40/53
2.6
89.3
38,571
39,764
1.07
0.97


3
500:1:0.05:0.05
TBABr
0.11
40/53
3.4
75.0
32,428
26774
1.15
1.21


4
500:1:0.05:0.05
TBABr
0.33
40/53
3.5
53.6
23,204
20,193
1.50
1.15





a - All polymerizations: [M] = 5.56M in MeCN, Temp = 30° C.,


bDetermined by 1H NMR.













TABLE 2







Polymerization of BA with potentiostatic conditions
















E
time
Conv.
Mn, theo
Mn, GPC



ATRP System
[M]/[I]/[L]/[CuII]
(V)
(h)
(%)
(g/mole)
(g/mole)
Mw/Mn

















BA/EBP/Me6TREN/CuIIBr2
300/1/0.2/0.2
−0.668
3.0
71.1
27,638
19,089
1.09





All polymerizations were conducted with [M] = 3.3M (50 (v/v) MeCN, [TBAPF6] = 0.1M, T = Room Temperature and reaction volume of 16 mL.













TABLE 3







Electrochemically mediated ATRP of MA as a function of applied potential.
















Exp.


E
[CuI]/[CuII]
time
p
Mn, theo
Mn, GPC



(#)
ATRP System
[M]/[I]/[L]/[CuII]
(V)
(target)
(h)
(%)
(g/mole)
(g/mole)
Mw/Mn



















1
MA/EBP/Me6TREN/CuIIBr2
500/1/0.2/0.2
−0.62
0.14
7.0
52
22,371
23,755
1.08


2
MA/EBP/Me6TREN/CuIIBr2
500/1/0.2/0.2
−0.69
1.0
5.0
83
35,271
26,795
1.08


3
MA/EBP/Me6TREN/CuIIBr2
500/1/0.2/0.2
−0.72
3.0
3.8
68
29,144
26,795
1.09





a - All polymerizations were conducted with [M] = 5.56M (50 (v/v) MeCN, [TBAPF6] = 0.1M, T = room temperature and reaction volume of 16 mL.






The final value for Mw/Mn=1.09 indicates an acceptable level of control throughout the reaction and the preparation of a well defined polymer. However minor tailing in the GPC curves indicates that further control could be exerted on the reaction if the applied charge was changed as the polymerization progressed.

Example 3
Electrochcmically Mediated Polymerization of Methyl Acrylate
3A. Selection of Appropriate Eapp 
As a consequence of these results a series of control CV's were performed to check for any additional reduction/oxidation reactions involving any of the other reagents, besides generation of the desired CuIIBr2/L complex, before conducting a second experiment, namely polymerization of methyl acrylate with CuIIBr2/Me6TREN. All CV's were conducted under conditions identical to that envisioned as suitable for the polymerization, i.e. those given in Table 3.
The initial evaluation was a potential sweep (i.e. CV) of the 50% (v/v) monomer/solvent reaction media, no significant oxidation or reduction was observed over a range of two volts, FIG. 3A. At this point, CuIIBr2 was injected into the reaction system and another CV was conducted, FIG. 3B. As expected, the CuIIBr2 solution in the mixture of monomer and solvent had a clear oxidation and reduction peak at positive potentials between 0.65 and 0.90 V (E1/2=0.780 V). Similar results are reported in literature for CuII salts, but it should be noted that these potentials are at different locations than may have been expected from prior analytical CV work on ATRP catalysts due to the selection of a different reference electrode; Ag/Ag+ instead of a saturated calomel electrode (SCE), which is based on the reaction between elemental mercury and mercury(I) chloride. These values can be converted to be SCE if required and indeed would be if the reference electrode is changed to ferrocene. In order to generate the additional information for an eATRP two additional CVs were performed by sequentially first adding the ligand, Me6TREN, FIG. 4 black curve, and then a low molecular weight initiator, ethyl 2-bromopropionate (EBP) was added and a significant shift in the E1/2 was observed, FIG. 4—grey curve.
This was the first time that a systematic CV analysis of precursors for an ATRP had been conducted and indicates that such a systematic analysis should be conducted prior to applying eATRP to a new monomer or with a new catalyst. The E1/2 was now ca. −0.67 V instead of 0.78 V vs Ag/Ag+. This curve was used as the base for all the polymerizations reported in Table 3 and for the Nernstian calculations. It should be noted that before each polymerization, a CV was run to check for any unexpected behavior and to confirm that the E1/2 was consistent with the results given in FIG. 4. Upon adding the initiator the shape of the CV changed, FIG. 4 gray line, which could now be expected due to the presence of additional CuIIBr2 generated in the presence of the initiator due to the reaction of the electrochemically generated CuIBr (Formula 3) re-oxidation reaction with the alkyl halide (Formula 4) to form a radical. Therefore additional cathodic current is required, which accounts for the CV curve remaining at a −2.0 μA instead of returning to −1.25 μA.

CuIIBr2/L+e−→CuIBr/L+Br−  (3)

CuIBr/L+RX→CuIIBr2/L+R−  (4)

The Nernst equation, shown below (Formula 5), was used to calculate the potential required to generate and maintain a variety of different [CuI]/[CuII] ratios from the CV shown as vertical lines in FIG. 4, grey curve w/o EBP, also shown in Table 3. At room temperature (RT/nF) is a constant, with a value of 0.02569 V, as our system is a one electron process (n=1).

E=E0+RT/nF Ln[O]/[R]  (5)

Indeed the Nernst equation can be employed to determine the absolute values for the concentration of each the activator and deactivator transition metal complex and the applied voltage can be selected to retain at least 0.1% of both the activator and deactivator in the contacting electrolyte when a controlled ATRP with an active catalyst complex is targeted for use in a polar medium such as water.
The changes in the shape and position of the CV measured in the presence of different components required for a controlled ATRP indicate that each polymerization reaction may require a similar set of measurements prior to selecting electrochemical conditions for formation of the desired ratio of oxidation states in the selected transition metal complex.
3B. Examination of Reaction Parameters
The first series of polymerizations of methyl acrylate were designed to probe the effect of changing the magnitude of the applied potential, Eapp. The results arc summarized in Table 3. Theoretically, assuming Nemstian behavior and a reversible system exists, the relative concentrations of [CuIIBr2/L] and [CuIIBr/L] should be tunable through the applied potential and concomitantly the polymerization rate. The first polymerization conducted with electrochemical control was conducted at the previously determined E1/2 value (Table 3, entry 2). Linear first order kinetics were observed and a good correlation between theoretical and experimental molecular weight values. A narrow Mw/Mn was observed throughout the polymerization and progressively increasing molecular weight of the polymers with conversion, as shown in the GPC traces of samples of polymer taken from the reaction after different times, and therefore at different degrees of monomer conversion (ρ), in FIG. 5. The curves moved cleanly to higher molecular weight.
Assuming a reversible or quasi-reversible system exists, as previously established with ATRP catalytic systems, the relative concentrations of CuIIBr2/Me6TREN and CuIBr/Me6TREN and concomitantly the polymerization rate should be tunable through the applied potential. Two additional polymerizations were conducted; one with an increase and the other a decrease of the applied potential; to −0.72 and −0.62 V, respectively, Table 3 entries 1 and 3. An enhanced polymerization rate was observed at the higher potential, a higher ratio of [CuI]/[CuII]=3.0, whereas a lower potential provided a lower ratio of [CuI]/[CuII]=0.14, and accordingly a reduced rate of polymerization.
Initial slopes in the first order kinetic plots revealed an approximate rate enhancement of 2.4 fold by adjusting the Eapp from −0.66 V to −0.72 V. The rate dependence should result from the adjustment of the relative concentrations of CuIBr/Me6TREN and CuIIBr2/Me6TREN, which dictate the overall rate of polymerization in ATRP. More negative potentials induce a faster reduction rate of CuIIBr/Me6TREN, and an increase in the [CuI]/[CuII] ratio, hence, results in higher rates of polymerization. In all cases, similar correlations between theoretical and experimental molecular weights were observed and narrow molecular weight distributions were maintained even with enhanced polymerization rates. GPC results illustrate clear shifts in molecular weight to higher values and monomodal distributions for all polymerizations.
3C. Switching a Polymerization Reaction “On” and “Off”
The final experiment in Table 4 was designed to demonstrate that designed changes in the applied potential could effectively “turn on” and “shut down” a polymerization. In the first hour of the experiment no potential was applied and no reaction occurred; no conversion of monomer was observed which shows that an applied potential is required to reduce a fraction of the CuII species to the CuI species and activate the polymerization. Then a potential of −0.693 V was applied for 45
minutes. During this time approximately 30% of monomer was consumed, FIG. 6—left. After 45 minutes the potential was changed to −0.45 V for 1 hour. The polymerization soon halted, although there was a 10-15 minute lag time as the low concentration of CuI species was slowly converted into the CuII species, once the change in the potential occurred. The time lag could be adjusted by varying the concentration of transition metal and/or the ratio of higher to lower oxidation states in the steady state. The reversible nature of this redox process and an ability to reinitiate polymerization was demonstrated by applying a potential of −0.693 V for 1 hour. As soon as this increased potential was applied, polymerization began again, increasing the overall consumption of monomer in the next hour to over 60%. Finally, the polymerization was switched off a second time by reverting to a less negative potential. The molecular weight values of the polymer chains correlated strongly with the theoretically predetermined values, FIG. 7—left scale, and a low Mw/Mn was maintained during the whole duration of the polymerization, FIG. 7—right hand scale. Lastly, GPC curves, FIG. 5B, showed that the molecular weight increased with conversion without any detectible coupling or substantial number of termination events.
3D. Examining Potentiostatic Outputs
In addition to the kinetic analysis of the polymerization, the potentiostatic outputs; total charged passed (Q) and current (I) values were recorded as the polymerization proceeded. Essentially dQ/dt (coulombs/s) is equal to the current (amperes (C/s)). From FIG. 8, it is clearly visible that more charged passed through the reaction during the polymerization than was required to completely reduce the total amount of CIIBr2 initially present in the reaction medium. Theoretically, if all CuIIBr2 







TABLE 4







Polymerization of MA under potentiostatic conditions

















Exp.


E1/2
E/t
[CuI]/[CuII]
time
Conv.b
Mn, theo
Mn, GPC



(#)
ATRP System
[M]/[I]/[L]/[CuII]
(V)
(V)/(h)
(target)
(h)
(%)
(g/mole)
(g/mole)
Mw/Mn




















1
MA/EBP/Me6TREN/CuIIBr2
500/1/0.2/0.2
−0.690
−0.690/1.0
1.0
4.8
69
28,500
24,542
1.12


2
MA/EBP/Me6TREN/CuIIBr2
500/1/0.2/0.2
−0.693
−0.693/5.0
1.0
5.0
83
35,271
26,795
1.08


3
MA/EBP/Me6TREN/CuIIBr2
500/1/0.2/0.2
−0.688
−0.716/3.8
3.0
3.8
68
29,144
26,795
1.09


4
MA/EBP/Me6TREN/CuIIBr2
500/1/0.2/0.2
−0.697
−0.668/7.0
0.33
6.8
75
32160
31645
1.10


5
MA/EBP/Me6TREN/CuIIBr2
500/1/0.2/0.2
−0.696
    on/off
1.0
4.8
67
28,856
24969
1.08





[a] - All polymerizations were conducted with [M] = 5.55M (50 (v/v) MeCN, [TBAPF6] = 0.1M, T = room temperature and reaction volume of 12 mL.


bDetermined by 1H NMR.













TABLE 5







Influence of [CuIIBr2/L] on AMP ATRP















Exp.


E
time
p
Mn, theo
Mn, GPC



(#)
ATRP System
[M]/[I]/[L]/[CuII]
(V)/h
(h)
(%)
(g/mole)
(g/mole)
Mw/Mn


















1
MA/EBP/Me6TREN/CuIIBr2
500/1/0.2/0.2
−0.668
7
75
32,160
31,645
1.10


2
MA/EBP/Me6TREN/CuIIBr2
500/1/0.05/0.05
−0.666
5.33
81
35,025
35,996
1.09


3
MA/EBP/Me6TREN/CuIIBr2
500/1/0.025/0.025
−0.666
5.33
91
38,918
31,337
1.06









was converted to CuIBr, then Q would equal 3.387 coulombs. This point is identified in FIG. 8 as point (b). This value is calculated by the product of the moles of CuIIBr2 put into the reactor (i.e. 3.51×10−5 mol) and Faraday's constant (9.64853×104 C/mol), Equation 6 below.





  
    
      
        
          
            Q
            ⁢
            
              
            
            ⁢
            
              (
              coulombs
              )
            
          
          
            nF
            ⁢
            
              
            
            ⁢
            
              (
              
                coulombs
                mol
              
              )
            
          
        
        =
        
          N
          ⁢
          
            
          
          ⁢
          
            (
            
              mol
              ⁢
              
                
              
              ⁢
              electrolyzed
            
            )
          
        
      
    
    
      
        (
        6
        )
      
    
  




The additional charged passed can be accounted for because in an ATRP as CuIBr is formed it reacts with alky halides thereby regenerating the corresponding CuIIBr2 species. A second point was identified as (a), were the charge passed and current change slope. These points arc of interest because this is the time when the level of control over polymerization begins to be reduced. Excessive reduction of CuIIBr2 could be responsible for this loss of control. This leads to the conclusion that a two step, or multi-step, potential is required to gain and retain optimum control throughout the polymerization. An initial higher potential to generate CuIBr quickly and then a lower applied potential to maintain the desired/targeted [CuIBr] while accounting for terminated chains. This value for applied potential should diminish as the reaction progresses. This is exemplified later in the optimal polymerization of methyl methacrylate (MMA), where in contrast to BA, a switching between two potentials provided the best possible control.
These results indicate that additional control of polymerization rate can be accomplished by applying different potentials at different periods of the polymerization and that it is necessary to maintain appropriate concentrations of CuI and CuII to preserve maximum control. The symmetrical GPC traces from entry 4 in Table 4 display a gradual increase in molecular weight, FIG. 5B, indicating a high level of control over the kinetics of the polymerization reaction.
Example 4
Control Experiments
While the above examples provide proof that electrochemical mediation of an ATRP is indeed possible a series of experiments was conducted in order to gain detailed information on how each component of the ATRP reaction medium influenced the overall level of control in order to provide parameters to expand the utility of the process to new catalysts, new polymerization media and new polymer architectures.
4A. Influence of the Concentration of Transition Metal Complex on Level of Control in an Electro-chemical ATRP Process
The concentration of transition metal complex, exemplified in the initial examples by cupric bromide in the presence of Me6TREN as the ligand, was progressively decreased from 400 ppm to 50 ppm. The reaction conditions/results are summarized in Table 5. As the concentration of catalyst was dropped from 400 ppm to 50 ppm three general trends were observed.

    
    
        Lower catalyst concentrations resulted in lower Mw/Mn values a polymer with a Mw/Mn distribution of 1.06, the lowest yet achieved while also achieving a high conversion.
        The 50 ppm system appeared to have the most linear first order kinetic behavior.
        As expected, lower amounts of catalyst resulted in a lower amount of charged passed, or species electrolyzcd.
    
    


Nevertheless at each concentration of catalyst, more charge was passed than required to reduce the initial CuIIBr2 present, indicating some termination reactions still occurred. The symmetrical GPC curves moved cleanly to higher molecular weight as conversion increased.
In one embodiment of the invention the reaction can be conducted with concentration of catalyst below 500 ppm, optionally below 100 ppm and optimally as low as 50 ppm.
4B. Influence of Initiators
The relative activity of each initiation system can be observed through the cathodic peak height compared to the CuII/CuI cathodic peak high without initiator present, FIG. 9. In each system the [M]=4.67 M and [TBAPF6]=0.2 M. Molar ratios=[M]:[I]:[CuIIBR2/L]=300:1:0.2. The left hand scale differs for FIGS. 9(A), (B), and (C). FIG. 9 shows this relationship with three initiators (EBPA, EBiB, and EBP) under conditions suitable for an ATRP polymerization. In this series of measurements the catalyst complex was formed with TPMA as ligand and cupric bromide as the transition metal salt. Moving from the most active to least active initiator, i.e. from the initiator with the lowest kact to that with the highest, the relative difference in cathodic heights becomes smaller. EBPA resulted in the largest difference while completely eliminating the anodic portion of the half wave. On the other hand, EBP resulted in very little difference and almost no change in the CV shape, indicating little catalytic activity of the alkyl halide. In addition to the relative activities of each initiator, slight variations in the catalyst complex half waves were observed. Methyl acrylate (MA) and methyl methacrylate (MMA) were the most similar and appeared to have more positive potentials indicating some stabilization of the electron transfer process, whereas styrene was the least positive and potentially the least stabilizing of the three monomers.
4C. Influence of the Concentration of the Monomer and the Initiator
Cyclic voltammetry measurements were carried out to investigate the influence of the concentration of the monomer and the initiator on the reaction. The system under study used the following components:
















Catalyst (precursor)
CuII(OTf)2, L = Me6TREN



Halide ion
Bromide



Initiator (I)
Methyl 2-bromopropionate (MBrP)



Monomer (M)
Methyl acrylate (MA)



Solvent (S)
Acetonitrile (AN)



Electrolyte (E)
Et4NBF4



Temperature
25° C.










The primary reactions involved during the electroregeneration of CuI in ATRP conditions are the following:

CuIIL+e⇄CuIL E0′CuIIL, k0ct,CuIIL/CuIL   (7)

CuIL+RX⇄X—CuIIL+R•KATRP, kact   (8)

R+M→R−M•kp   (9)

X—CuIIL+e⇄X—CIL E0′XCuIIL/XCuIL, k0ct, XCuIIL/XCuIL   (10)

X—CuIL⇄CuIL+X−1/KCuIL+X, kd,XCuI1.   (11)

Considering CuIL as the species responsible for the activation of RX (reaction shown in equation 8), the rate of polymerization, or degree of catalysis, is directly correlated with its rate of regeneration, which in principle depends on reactions (7), (10) and (11). If we consider a rather active initiator like MBrP (kact ̃2000 M−1s−1 in pure CH3CN), after reaction (7) the concentration of CuIL near the electrode surface is very low because of the homogeneous activation reaction (8); furthermore, after one catalytic cycle all the CuII is present as XCuIIL (logBrCuIIL=6.1 in pure CH3CN), and therefore the electrodic process correlated with the degree of catalysis is underlined by the reaction (10). FIG. 10 reports the effect of the concentration of initiators on the voltammetric cycle recorded starting with CuIIL, recorded at v=0.05 V/s on Pt, in AN/MA 1:1+0.1 M Et4NBF4. The first cathodic wave is the monoelectronic reduction of CuIIL (reaction 7): in absence of initiator, this is the only process involved since the catalytic cycle can not switch on. Therefore, the voltammetric response is totally reversible. After the addition of an initiator, MBrP, a second wave appears at more negative potential, because of the reduction of XCuIIL produced by the homogeneous reaction (8), and the reversibility of the first peak is lost since the concentration of CuIL is very low. In the presence of higher ratios of [MBrP]/[CuIIL] the cathodic peak current Ipc,XCuIIL increases, meaning higher degrees of catalysis.
4D. Influence of the Concentration of the Monomer and Solvent
The same approach was used to investigate the effect of the monomer/solvent ratio on the degree of catalyst activity. The CV of 1 mM CuIIMe6TREN in the presence of 10 mM MBrP and 0.1 M Et4NBF4 at different AN/MA ratio+0.1 M Et4NBF4, recorded at v=0.05 V/s on Pt. V0=15 mL, MA step addition=5 mL. In this case, the experiment was influenced by a certain approximation. In fact, the MA step additions entail dilution of the reaction medium; this problem was overcome considering the direct proportionality between the peak current Ip and the bulk concentration of the electroactive species C*, given by the Randles-Sevcik equation (12):




  
    
      
        
          I
          p
        
        =
        
          0.4463
          ⁢
          
            
          
          ⁢
          n
          ⁢
          
            
          
          ⁢
          FAC
          *
          
            
              (
              
                nF
                RT
              
              )
            
            
              1
              ⁢
              
                /
              
              ⁢
              2
            
          
          ⁢
          
            D
            
              1
              ⁢
              
                /
              
              ⁢
              2
            
          
          ⁢
          
            v
            
              1
              ⁢
              
                /
              
              ⁢
              2
            
          
        
      
    
    
      
        (
        12
        )
      
    
  




It was assumed that the changes in the diffusion coefficient D after the MA stepwise additions were negligible. The voltammetric responses are quite similar to those shown in FIG. 10; however, increasing the ratio MA/AN results in a slight reduction in the activity of the catalyst, since the reduction peak current Ipc. of XCuIIL decrease with higher ratio MA/AN which indicates that catalyst activity changes with comonomer/solvent ratio and the correct potential should be selected and applied for maximum control.
4E. Selecting the Applied Potential
Selecting the correct applied potential, Eapp is of primary importance when conducting potentiostatic electrolysis. In particular, two main conditions can be used:

    
    
        electrolysis under diffusive control: in this case, Eapp<<Epc and the overall rate of the reaction is controlled by the rate of the diffusion of the reactants to the electrode surface rather than the rate of the reaction itself or;
        electrolysis under kinetic or chemical control: herein, Eapp≧Epc and the overall rate of
    
    


the reaction is controlled by the rate of the reaction itself rather than the rate of the mass transport of the reactants to the electrode surface.
In addition to these considerations, the choice of Eapp should be appropriate in order to avoid other undesired electron transfers. In ATRP systems, one of these factors is the further reduction of CuI to Cu0, this is expected to occur at potentials more negative than that of the CuII/CuI redox couple when disproportionation is not thermodynamically favoured. FIG. 11, which shows the CV of 1 mM CuIIMe6TREN in the absence (a) and presence (b) of 1 mM Et4NBr, recorded at v=0.05 V/s on Pt, in 0.1 M Et4NBF4+0.1M Et4NBF4, confirms these expectations: the first cathodic peak, curve (b), corresponds to the reduction CuII/CuIL, whereas the second peak, curve (a), at, at more negative potential is indicative of electrode position of Cu0 on the electrode surface, since the back scan is characterized by the so-called anodic-stripping peak, having the typical symmetric shape with high peak current. During this process, the electrodeposited Cu0 is oxidised to CuI ion that undergoes complexation in solution and subsequent oxidation to CuIIL. This electrochemical picture is confirmed when the starting species is Br−CuIIL, FIG. 11 curve (b) in this case, both the BrCuIIL/BrCuIL and BrCIL/Cu0+Br+L redox processes are shifted toward more negative potentials because of the stabilization induced by the halide ion, while the anodic stripping is unchanged since it is independent of the presence of the ligands in solution.
These observations point out that there is always a lower limit for Eapp in order to avoid the electrodeposition of the transition metal; furthermore, the presence of 1 equivalent of halide ion is necessary to produce the ternary complex BrCuIIL to investigate Eapp in the diffusive region of the BrCuIIL/BrCuIL redox couple.
The results also confirm that copper can be removed from the reaction by electrodeposition and that the catalyst complex can be reformed by reaction of deposited Cu0 with ligands present in the reaction medium.
4F. Influence of Solvent
The next series of reactions were designed to evaluate the influence of solvent. Numerous reports in incorporated references have shown well controlled ATRP reactions occur in DMSO as solvent. One reaction was conducted with DMSO as solvent, this required a new reference electrode, and exhibited an initially faster reaction in comparison to the reactions conducted in MeCN. The DMSO system experienced a significant exotherm, which would have further increased the kp of methyl acrylate. Nevertheless two advantages of the DMSO system should be noted:

    
    
        no clogging of the vycor frit was noticed and
        DMSO will allow further expansion in the selection monomers that can be polymerized by eATRP to include more polar monomers, if it is selected as the solvent.
    
    


Anisole is a more hydrophobic solvent than acetonitrile. In the initial evaluation of the CV analysis when using such a hydrophobic solvent (i.e. low conductivity) high solvent resistance was observed. In response to this, the molarity of supporting electrolyte was increased from 0.1 M to 0.2 M to achieve better conductivity. Furthermore, since it is the IUPAC standard, it was considered important to begin reporting standard potentials against ferrocene. FIG. 12 illustrates two couples; one of the copper ligand complex (CuIIBr2/TPMA) and the ferrocene/ferrocenium standard. A difference of ca. 0.72 V exists between the two couples.
The first polymerization conducted in anisole was methyl acrylate. This monomer was chosen because of the success in the MeCN system. Cyclic voltammetry was conducted of the solvent and monomer background and a limited current was observed in a range of 3.5 V reflecting the relative stability of the system. Further CV analysis was carried out, shown in FIG. 9C, by first recording the copper complex of interest and then after addition of the alkyl halide initiator. Methyl acrylate was successfully polymerized by eATRP in anisole at T=50° C. High conversion values over 90% within 5 hours, linear first order kinetic behavior was observed, and a linear increase in molecular weight with conversion was observed with Mw/Mn values around 1.1 which shows that no significant coupling is occurring during polymerization.
Example 5
Polymerization of Methyl Methacrylate
5A. As previously discussed background CVs of the solvent and monomer were carried out along with characterization of the initiator activity. Similar to the MA system a 3.5 V range was observed and no significant current passed until reaching the cathodic and anodic discharges. EBPA was selected as the initiator for MMA as it showed high activity in the CV analysis, FIG. 9A. To further exemplify that eATRP can be applied to a range of catalysts a copper triflate based catalyst, CuII(Trf)2/L. was used in conjunction with one equivalent of TBABr to convert the complex to their more active CuIIBr/L catalyst. A background of MMA/anisole with supporting electrolyte (TBAPF6) was conducted and no significant current passed, either cathodically or anodically, from ca. −1.5 to 2 V showing the stability of the reaction medium. After confirming the stability of the reaction medium, CuII(Trf)2/TPMA was injected into the reaction medium and an additional CV was recorded. A reversible couple was observed at ca. 0.659 V that shifted to 0.315 V after addition of the bromine electrolyte. This corresponds to ca. 0.344 V more negative potential. After addition of the copper catalyst, the initiator was introduced to the system. Since the monomer to be polymerized was MMA, EBPA was selected as the initiator. The CVs were recorded before and after addition of the initiator and as expected, a large increase in the cathodic current and decrease in the anodic current were observed, since with a very active initiator such as EBPA, a large portion of the electro-generated CuI is converted back into CuII.
FIG. 13 shows a typical current versus time profile of the MMA system in anisole where the CV's were conducted periodically during polymerization. Polymerisation conditions: [MMA]=4.5 M, [MMA]:[EBPA]:[TPMA]:[CuII]=300:1:0.1:0.1, T=50° C. Two current profiles are shown which represent the two polymerizations conducted. The black curve is that of the Eapp=Epc, having initial current values between −1 mA and −0.4 mA, whereas Eapp=E1/2 had current values at a maximum of −0.4 mA. The high current values (black line) in combination with EBPA are most probably responsible for the early termination events occurring in the cathodic peak system. Based upon this assumption, a system where CuI is slowly fed into the polymerization system would generate better results. Nevertheless, the eATRP in anisole was proven to be a successful system for MMA. The eATRP of MMA conducted at T=60° C. resulted in a successful polymerization. Near quantitative consumption of monomer (ca. 98-100%) was observed and linear first order kinetics. The molecular weight increased linearly with conversion although it was slightly lower than the theoretical values and the molecular weight distribution was narrow (Mw/Mn≦1.3) the current profile resembled that of the MA system except with different time scales, each reaching minimal current values around −200 mA.
5B. Optimization of MMA Polymerization
TBAClO4 (4.69 mmol, 1.6051 g), was added to an electrochemical cell equipped with the electrodes and a condenser and flushed with nitrogen. Deoxygenated DMF (13.1 mL) and MMA (0.0907 mol, 9.7 mL) were transferred into the cell via gastight syringe. A stock solution CuII/TPMA/Br− in DMSO (0.027 mmol, 0.18 mL for 300 ppm reactions, [CuII]=0.15 M; 0.009 mmol, 0.18 mL for 100 ppm reactions, [CuII]=0.05 M) was added and subsequently bubbled with nitrogen. A CV of the CuII/CuI couple was conducted to detect the possible range of applied potentials Eapp. The initiator EBPA (0.3 mmol, 0.053 mL) was added, followed by further bubbling for 10 min. A CV of the CuII/CuI initiator system was conducted. Several potentials were defined on the basis of cathodic and anodic peak potential value (Epc and Epa, determined by CV).
Within this application the average potential between Epc and Epa is defined as E1/2. The potential difference Δ=E1/2−Epc was defined and subtraction of Δ from Epc was assigned as E1/2. The average potential between Epc and E1/2 was defined as E1/4. FIG. 14 illustrates their location within the CV of the CuI/CuII couple. The reaction was started by applying the selected Eapp.
The current profile of the eATRP of MMA using EBPA as initiator, showed a significant drop in current after a certain time, the time that this drop is observed is defined as tdrop, and subsequently continued trending downwards, see FIG. 15(A). Application of a more negative potential or conducting the reaction at a higher temperature decreased the time period until tdrop occurred. Comparison of the current profile shape shows that a much higher slope of the current occurs in electrolysis of BA using EBiB, FIG. 15(B), as initiator than for MMA with using EBPA.
Table 6 summarizes the reaction conditions for the polymerization of MMA in which variation and switching of applied potential during the reaction and the corresponding time tdrop; variation of temperature and initial CuII catalyst concentration are summarized.







TABLE 6







Application of two different applied potentials to an eATRP













Reac-


Temper-
CuII
tdrop
k


tion
Eapp, 1
Eapp, 2
ature[° C.]
[ppm]
[min]
[hr−1]
















16.4
E1/4
E1/4
60
100
80
0.71


16.5
Epc
Epc
45
100
130
0.28


16.6
E−1/2
E1/2
40
100
45
0.21


16.7
E−1/2
Epa
40
100
50
0.10


16.8
E−1/2
E1/2
40
300
40
0.35


16.9
E−1/2
Epa
50
300
30
0.57









These experiments show that switching of the applied potential from a more negative potential to a more positive potential after tdrop, and decreasing reaction temperature not only improved the polydispersity but it also reduced the induction period and improved the symmetry of the GPC signals due to less formation of shoulders at higher molecular weight and less tailing at lower molecular weights.
Therefore in one embodiment of the invention two different applied potentials are applied to improve the overall level of control in an electrochemically mediated ATRP, the first a more negative potential to rapidly reduce the higher oxidation state transition metal complex to the lower oxidation state then a more positive potential to maintain the targeted ratio of two oxidation states of the transition metal complex.
Example 6
Exemplifying eATRP for a Broader Range of Monomers
The following examples expands the range of monomers by exemplifying application of an eATRP to a broader variety of monomers by defining conditions appropriate for the polymerization of ethyl acrylate (EA), butyl acrylate (BA) and styrene (sty).
6A. Polymerization of Butyl Acrylate
Run conditions were [BA]/[EBiB]/[TPMA]/[CuIITrf2]/[TPMA]/[TBABr]=300/1/0.03/0.03/0.03, [BA]=3.87 M (43 (v/v) % in DMSO:Anisole), [TBAClO4]0.2 M, T=40-45° C. FIG. 16A provides the CV traces of the Cu species under a variety of conditions prior to electrolysis. As expected, addition of Br− to the system shifted the CuII/CuI catalyst couple ca. 200 mV (black to grey trace). Next, after addition of the initiator a large catalytic response was observed due to the regeneration of CuII (dashed trace). FIG. 16B shows the current and charge passed versus time. A rapid decay in current was observed approaching negligible values (10-15 uA). Rapid conversion of CuII to CuI is observed in the early stages whereas a minimal amount of charge is required to maintain the CuII/CuI ratio. GPC for polymer samples collected during both experiments show narrow monomodal distributions of the polymeric species.
After conducting the initial experiments detailed above in Examples 2 and 6A, it was decided it would be appropriate to use DMF instead of DMSO as it provided several additional advantages including: (1) enhancement of KATRP ̃in comparison to anisole, (2) increase the conductivity of the reaction medium, there is a large drop in resistance when incorporating DMF versus anisole, and (3) improve the solubility of Sty, MMA, and BA polymers in the reaction medium.
6B. Optimizing Reaction Conditions for Polymerization of Butyl Acrylate
6B 1) [BA]/[EBiB]/[TPMA]/[CuIITrf2]/[TPMA]/[TBABr]=300/1/0.09/0.09/0.09, [BA]=3.87 M, [TBAClO4] 0.2 M, T=44° C. 300 ppm catalyst was used in each instance. Three different voltammograms were obtained for the polymerization mixture prior to electrolysis, FIG. 17A. As expected, a typical copper couple was observed with quasi-reversible behavior in reference to Ag/AgI. Anodic and cathodic peaks were separated by ca. 80 mV under fully compensated conditions. After addition of an initiator a large catalytic response was observed due to the regeneration of CuII resulting in an increased cathodic response. Each of these voltammograms was conducted under typical stagnant conditions. The final CV was conducted with stirring. Three clear regions were observed: (1) onset of reduction of CuII (2) a proportional/linear increase in cathodic current with potential and (3) a limiting current region (at diffusion controlled limits). An equation was developed which describes the limiting current value (i1(f)) as a function of time when using a potential value within the limiting current region. This specific CV indicates where no further rate enhancement is possible by providing a more negative potential.
6B 2) Reaction conditions: [BA]/[EBiB]/[TPMA]/[CuIITrf2]/[TPMA]/[TBABr]=300/1/0.09/0.09/0.09, [BA]=3.87 M, [TBAClO4] 0.2 M, T=44° C. Four different polymerizations were conducted with identical formulations but increasingly more negative potentials. A clear trend is observed, FIG. 17B: increasingly negative potentials provide an increase in apparent rate coefficients. However, a limiting region exists somewhere between 80-120 mV past the Epc whereby a small rate enhancement was observed. Surprisingly the molecular weight and Mw/Mn data in each experiment displayed similar behavior. When applying more positive potential (Ep and E1/2) lower Mw/Mn values were observed indicative of the presence of a larger amount of CuII in the system. Rapid conversion of CuII to CuI is observed in the early stages, typically less than 30 minutes whereas a minimal amount of charge is required to maintain the CuII/CuI ratio. Also the initial current values were larger with a larger Eapp which generally can be related to the rate of reduction of CuII to CuI and therefore indicates the relative concentration of CuII 
6B 3) Reaction conditions: [BA]/[EBiB]/[TPMA]/[CuIITrf2]/[TPMA]/[TBABr]=300/1/X/X/X, [BA]=3.87 M, [TBAClO4]0.2 M, T=44° C. The next variable which was investigated was the concentration of CuII initially added to the system. The Eapp in all instances was 80 mV more negative than the cathodic peak potential (Epc). It was predicted that higher concentrations of copper should yield increased rates of polymerization and lower Mw/Mn values. Pseudo-first order kinetic plots were generated to examine the function of the concentration of copper. As the concentration of copper increases the rate of polymerization was observed to increase to a root dependence of the relative copper concentrations. The increase in molecular weight was linear with respect to conversion in all cases, however, the CuII concentration had a profound impact on the Mw/Mn values as the polymerization proceeded with higher concentrations of copper leading to lower Mw/Mn values. As we know the Mw/Mn value corresponds to the following equation:




  
    
      
        
          
            M
            w
          
          
            M
            n
          
        
        =
        
          1
          +
          
            1
            
              DP
              n
            
          
          +
          
            
              (
              
                
                  
                    
                      [
                      
                        R
                        -
                        X
                      
                      ]
                    
                    o
                  
                  ⁢
                  
                    k
                    p
                  
                
                
                  
                    k
                    da
                  
                  ⁡
                  
                    [
                    
                      X
                      -
                      
                        Cu
                        II
                      
                    
                    ]
                  
                
              
              )
            
            ⁢
            
              (
              
                
                  2
                  q
                
                -
                1
              
              )
            
          
        
      
    
    
      
        (
        2
        )
      
    
  




The current profiles also reflect the relative concentration of CuII in the system.

6B 4) In an effort to further improve the eATRP process the effect of minimization of the supporting electrolyte was investigated. Reaction conditions:

    [BA]/[EBiB]/[TPMA]/[CuIITrf2]/[TPMA]/[TBABr]=300/1/0.9/0.9/0.9, [BA]=3.9 M, [TBAClO4]=X M, T=44° C. The Eapp in all instances was 80 mV more negative than the cathodic peak potential (Epc). The relative resistance of the reaction medium was clearly observed when decreasing the concentration of TBAClO4 and the resistance values were progressively increased from 500 to 14,500 ohms at 0.2 M to 0 M, respectively. When examining the rate of polymerization as a function of supporting electrolyte, a visible reduction in the apparent rate constant can be observed as the concentration of supporting electrolyte is decreased. When no supporting electrolyte was used polymerization still occurred, however a large induction period was observed. Without being limited by the proposed mechanism it is believed that the decrease in the rate of polymerization can be explained as a result of an increase in the resistance of the solution. When all process involved in the reaction are fast, this leaves the electron transfer of the reaction as the limiting factor. Measurements of the electron transfer constant for the electrode (Γsec)) are determined in the following equation:

Γ=RsCd   (18)

were Rs [Ω] is the solution resistance and Cd [F] is the capacitance.



Therefore, as the solution resistance increases the time of electron transfer become longer and ultimately slows the polymerization (this phenomena is also in relation to migration of ions to the WE and CE). This is bolstered by the current profiles where a decrease in current is observed with less supporting electrolyte. However the change in rate had no effect of either Mn or Mw/Mn.
In one embodiment of the invention the rate of polymerization is modified by the concentration of the added electrolyte.
6C. Polymerization of Styrene
TBAClO4 (4.69 mmol, 1.6051 g) was added to an electrochemical cell fitted with the electrodes and a condenser then the flask was flushed with nitrogen prior to the addition of deoxygenated DMF (12.4 mL), and styrene (0.0907 mol, 10.4 mL) via a gastight syringe. A stock solution of CuII/TPMA/Br− in DMSO (300 ppm of CuII, 0.027 mmol, 0.18 mL, [CuII]=0.15 M) was added then the reaction mixture was bubbled with nitrogen for 15 min. A CV of the CuII/CuI couple was conducted to detect the cathodic peak potential Epc. The initiator EBiB (0.3 mmol, 0.044 mL) was added, followed by further bubbling with nitrogen for 5 min. then the CV of the CuII/CuI+initiator system was conducted. The reaction was started by applying the cathodic peak potential Epc at a temperature of 90° C. The experimental molecular weights were slightly higher than the theoretical, which suggests termination of radicals in the early phase of the reaction however the GPC signal did not show any shoulder at higher molecular weights, nor significant tailing to lower molecular weight region.
Example 7
Preparation of Polymers with more Complex Topologies
The anisole system was in part developed in order to be directly applicable to synthesis of more complex architectures through eATRP. Anisole, in addition to being suitable solvent for a wide range of monomers, is also commonly used in the synthesis of stars and brushes through ATRP.
7A PnBA-stars. The first eATRP synthesis of star macroraolecules was attempted with PnBA-Br macroinitiators under potentiostatic conditions. Starting conditions for star synthesis: [PnBA]=0.02 M, [PnBA]:[DVB]:[TPMA]:[CuII]=1:12:0.2:0.1, T=90° C. An initial CV was recorded for the macroinitiator (MI) to determine a suitable potential for synthesis of PnBA stars, which was selected to be at the cathodic peak, indicated by dashed circle in FIG. 18(A). The decay of current was slower than typical eATRP polymerization systems, and reached a near steady state at ca. −0.05 mA, FIG. 18(B). Once the current reached its steady state no additional MI's were incorporated into the star. In addition, the mmol of CuII electrolyzed during star synthesis never reached full conversion of the initially added CuII. The Eapp would correspond to a radio of [CuII]/[CuI]= ̃0.07, meaning that a maximum of ca. 14 mmol should have been possible. This experiment showed that ca. 11 mmol of CuII was converted to CuI. The GPC traces of samples collected as the polymerization progressed showed almost quantitative consumption of the macroinitiators, although a small tail was observed in the final star indicating that some lower molecular weight species existed, which were either a result of terminated chains during macroinitiator synthesis or from termination reactions during the activation stage of the star synthesis from the added macroinitiators. NMR revealed near complete consumption of divinyl benzene (DVB) after ca. 9 h. The final molecular weight and molecular weight distribution of the star polymer was 60,000 g/mol and 1.40 respectively.
Example 8
Controlled Aqueous ATRP of OEOMA
CuII/ITMA, which is one of the most active complexes used in ATRP, was chosen as the catalyst system. In cyclic voltammetry screening the CuIIL2+ exhibits a reversible peak couple with Eo′=−0.245 V vs SCE, FIG. 19. Addition of a large excess of Br− to the solution does not significantly affect this CV response, indicating that the KX of CuIIL2+ is very small, FIG. 20 curve a. The full reversibility of the response at very low scan rates confirms that CuIL+ is quite stable in H2O with a lifetime of at least few seconds, the time scale of CV. Using the above reported Eo′value together with other available thermodynamic data, the value of KD was estimated to be 6.8×10−3 for the disproportionate of CuIL+. The CV response of CuIIL2+ drastically changes when an equimolar amount of the initiator, 2-hydroxyethyl 2-bromoisobutyrate (HEBriB) is added, FIG. 20 curve b. The cathodic peak approximately doubles in height while the anodic one decreases, clearly indicating that CuIL+ rapidly reacts with HEBriB. On the basis of thermodynamic data available in the literature, the estimated KATRP value for this system is 1.5×10−1, which is 4 orders of magnitude higher than that measured for an analogous system in CH3CN. An estimate of the activation rate constant based on voltammetric analysis of the system CuIIL2++HEBriB at different concentration ratios are shown in FIG. 20 curves b and c, and different scan rates provide a very large value for kact≧2.5×106 M−1s−1.
The above described voltammetric analyses show that the system under investigation has all the characteristics that make aqueous ATRP reactions very difficult to control; low KX, high KATRP, and extremely rapid activation. Therefore, it represents an excellent test of the potential of the proposed electrochemical method to resolve problems still facing application of ATRP to certain systems, herein exemplified by aqueous ATRP.
The electrogeneration of the active catalyst was carried out under potentiostatic conditions starting from the catalytic system CuIIL2+/HEBriB 1:1 in H2O+10% OEOMA475 (MW=475 gmol−1). The effect of Eapp on the degree of control over polymerization was first investigated. Three Eapp values around Eo′ were applied, points marked on FIG. 19, and the results are summarized in Table 7 (entries 1-3). The driving force of the electrochemical process is given by ΔGo=F(Eapp−Eo′) and the [CuIIL2+]/[CuIL+] ratio at the electrode surface is closely related to that dictated by the Nernst equation. At the beginning of the electrolysis there is only CuIIL2+ in solution, so the current has to decay as CuII is converted to CuI, approaching a constant value corresponding to the [CuIIL2+]/[CuIL+] ratio required by Eapp. However, CuIL+ is engaged in a reversible reaction with the initiator and the formed dormant species, which represents a continuous perturbation to the equilibrium concentrations imposed by Eapp. Therefore, whether a constant [CuIIL2+]/[CuIL+] ratio can be imposed in the bulk solution depends on the mutual rates of electrogeneration and disappearance of CuIL+ and therefore will depend on Eapp.
At Eapp=−0.55 V, which is <<Eo′the electrode process is under diffusion control and CuIIL2+ is almost quantitatively converted to CuIL+ in a relatively short time; the current rapidly decreases to very small values. The overall rate of the process was rather high, with 79% of monomer conversion in less than 30 min, but control over polymerization was poor. The ln([M]/[M]0) vs time plot deviated significantly from linearity, while the molecular weight distribution of the formed polymer was very broad and the final experimental Mn was 3 times larger than the theoretical one, Table 7, entry 1. These features are typical of an uncontrolled polymerization dominated by termination reactions, such as bimolecular radical-radical coupling reactions.
With Eapp=−0.31 V, the current decays much less rapidly than in the case of the electrolysis at −0.55 V, but tends to a constant value after a long period. Under these conditions, the rate of polymerization decreased without significant improvement in the control, Table 7, entry 2.
With Eapp=−0.21 V, the current decays very slowly, approaching a constant value ( ̃−250 μA) within a short period. Under these conditions Eapp>Eo, which implies an equilibrium [CuIIL2+]/[CuIL+] ratio >>1. In this case, the process is under a good control as judged by the linearity of the first-order kinetic plot, Mn increases linearly as a function of monomer conversion and polymers with Mw/Mn ̃1.2 are obtained and nearly quantitative monomer conversion. This striking improvement of control is achieved with low charge consumption. This is a clear evidence of a drastic decrease of the termination events due to a good balance between [CuIL+] and [CuIIL2+].
To promote the formation of XCuIIL+ some experiments were run in the presence of a large excess of X− (Table 7, entries 4-5). As shown, the presence of X− produces a noticeable improvement of MW distribution without any loss in the rate of monomer conversion. Furthermore, the overall rate of the process does not decrease due to the formation of inactive CuIXn species as was found in organic solvents when excess X− is added. [Macromolecules, 2010, 42, 9257-9267; Chem. Commun. 2011, 47, 3580-3582.] Linear first-order kinetic plots were observed for all the polymerizations carried out with [CuIIL2+]=0.1 mM, FIG. 21. In particular, experiments with different degrees of polymerization gave a fairly constant slope, d(ln [M]0/[M])/dt, suggesting that the radical concentration is unaltered.
8B. eATRP of OEOMA475 in Water in the Presence of Added Salts
PBS buffer was selected as an exemplary salt since it is employed in reactions seeking bio-conjugation of a protein with a water soluble polymer. Since Eo′ shifts to −0.326 in this medium Eapp was adjusted to −0.275 V. Although several interferences perturbing the ATRP equilibrium are possible (e.g., highly insoluble CuII3(PO4)2 and/or stable CuI(H2PO4)2− and CuICl2− may form [Chem. Commun. 2011, 47, 3580-3582], excellent results were observed both in terms of conversion and Mw/Mn, Table 7, entry 5. Indeed, neither displacement of the ligand nor loss of catalysis was observed by CV analysis of the system.
The effect of targeting different DPs was explored (Table 7, entries 6-8) using 0.1 mM CuIIL2+, 6.4 mol ppm with respect to solvent, and different concentrations of monomer. All polymerizations displayed linear ln([M]/[M]0) vs time plots which, together with low Mw/Mn values of the final polymer, is indicative of ATRP under good control. However, the experimental Ma was significantly higher than the theoretically predicted one. This is due to low initiation efficiency at the beginning of the polymerization. Improvement was obtained with PBS buffer, Table 7, entry 9.
In conclusion, aqueous eATRP overcomes the most serious drawbacks associated with conventional aqueous ATRP. The balance between CuIIL2+ and CuIL+, which is crucial for control, can be regulated by appropriate selection of Eapp by following the simple CV analysis herein disclosed for each targeted monomer and initiator. The best results were achieved at Eapp<E0Cu(II)LCu(I)L, providing excellent control over MW and MW distribution, accompanied by a fast reaction and a low charge consumption. Remarkably, phosphates and halide ions can not only be tolerated but can have a beneficial effect on the level of control over the polymerization. This last observation could be attractive for biological systems.
Example 9
eATRP Minicmulsion
Initial experimentation involved preparation of a miniemulsion and characterization using CV. CV traces representing the cathodic and anodic discharges of the miniemulsion system were examined in the absence of Cu/TPMA, FIG. 22. When viewing CV's conducted in the cathodic direction the reduction of protons begins around −1.6 V to generate H2 whereas in the anodic direction oxidation of water occurs to generate O2 at around 1 V, these discharges may not be water but rather monomer. Upon closer examination of the cathodic CV a small current response can be seen around between 0.2 and −0.1 V, indicative of the presence of Cu/BPMODA catalyst in the system. Larger potentials were not probed in these CV experiments due to passivation of the electrode. After identifying the current response of CuII/BPMODA further scans were recorded at various scan rates. As expected, the BPMODA couple current increased with increasing scan rate. The larger scan rates allowed accurate identification of the catalyst couple. The intensity of the current indicates that the catalyst complex is for the most part inaccessible to the electrode and resides within or at the surface of the miniemulsion particles or organic phase.
The addition of CuII/TPMA significantly changed the response, FIG. 22. The TPMA response resembles that of a transition metal complex participating in catalytic behavior, as indicated by the large cathodic and small anodic current. This behavior indicates that CuII/TPMA is regenerated by participating in homogenous bulk reactions, presumably those shown in the following equations, direct activation of the initiator (14) and electron transfer with CuI/BPMODA (15):

CuI/TPMA+RXCuII/TPMA+R•  (14)

CuI/TPMA+CuII/BPMODA→CuII/TPMA+CuI/BPMODA  (15)

In addition the large current response indicates that Cu/TPMA is assessable to the electrode and remains mostly within the aqueous phase.








TABLE 7







Electrochemical aqueous ATRP of OEOMA475 at 25° C.

















Entry
% M v/v
[M]/[RX]/[CuIIL]
Electrolyte[c]
Eapp (V vs SCE)
t (h)
Q (C)
C %[e]
10−3 Mn, theor
10−3 Mn, exp[f]
Mw/Mn




















1
10
200/1/1/[a]
Et4NBF4
−0.550
0.5
3.05
79
75.1
233
1.58


2
10
200/1/1[a]
Et4NBF4
−0.310
1.8
4.34
88
83.2
213
1.53


3
10
200/1/1[a]
Et4NBF4
−0.210
3.0
2.65
98
93.1
112
1.22


4
10
200/1/1[a]
Et4NBr
−0.210
2.5
2.32
99
94.0
109
1.16


5
10
200/1/1[a]
PBS buffer[d]
−0.275
3.0
1.94
98
93.1
130
1.15


6
5.0
1000/1/1[b]
Et4NBr
−0.210
2.0
0.175
84
399
704
1.25


7
2.5
500/1/1[b]
Et4NBr
−0.210
2.0
0.210
72
171
403
1.19


8
1.0
200/1/1[b]
Et4NBr
−0.210
2.5
0.267
77
73.2
175
1.35


9
5.0
1000/1/1[b]
PBS buffer[d]
−0.275
2.0
0.179
79
375
450
1.20





[a][CuIIL2+] = 1 mM.


[b][CuIIL2+] = 0.1 mM.


[c]0.1M.


[d]0.137M NaCl + 2.7 mM KCl + 11.9 mM (Na2(HPO4) + KH2PO4) in H2O; pH = 7.4.


[e]Determined by 1H NMR.


[f]Determined by GPC-MALLS













TABLE 8







Summary of miniemulsions by eATRP.



















Ent.
Exp.
Eapp
Temp.
[HD]:[Brij]a
Solidsb
[E]
DLS
time
pNMR





(#)
(#)
(V)
(° C.)
wt. (%) vs M
(%)
M
nm/PDI
(h)
(%)
Mn, theo
Mn, GPC
Mw/Mn






















1
2-79
−0.550
65
5.4:4.6
19.7
0.019
143/0.147
10
n/a
n/a
22,751
1.96


 2c
2-80-1
−0.310
65
5.4:4.6
19.7
0.019
131/0.162
2.5
n/a
n/a
39,110
14.1


3
2-82
−0.296
65
3.7:4.6
19.7
0.020
143/0.147
4.0
63.8
32,941
17,238
1.93





All reactions have the following molar ratios: [BA]/[EBiB]/[BPMODA]/[TPMA]/[CuII] = 400/1/0.4/0.4/0.8


a(mHD/mBA)*100.


bsolid content = (mBA/(mtot−melectro))*100.


cwithout Cu/BPMODA






A series of control experiments were conducted to investigate the origin of the CuII/TPMA catalytic response, as shown in FIG. 23(A). The black curve represents a miniemulsion system formulated with both TPMA and BPMODA ligands and EBiB as initiator. This CV represents the total catalytic response from both CuII/BPMODA and EBiB interacting with CuI/TPMA. A second miniemulsion was then formulated without CuII/BPMODA which is represented by the dark grey curve. As evident from the CV, there is a substantial decrease in the current response when CuII/BPMODA is not present. This result confirms that indeed CuI/TPMA interacts with CuII/BPMODA. A third formulation was made, where initiator was not added, which also resulted in a significant decrease in current as compared to the system containing all reagents (light grey curve). These results confirm that both chemical pathways exist simultaneously and may indicate that CuI/TPMA reacts at a faster rate with EBiB than with CuII/BPMODA.
FIG. 23(B) represents a miniemulsion formulated without EBiB while still containing CuII/BPMODA. TPMA ligand, that had not been precomplexed with Cu, was then added to the reaction medium. Interestingly, the TPMA complex couple appeared (black curve) which indicates that ligand exchange occurred. The TPMA effectively stole the Cu from the preformed Cu/BPMODA complex. Afterward, a second charge of CuII was added for complexation with TPMA which resulted in an increase in current as expected (grey curve).
After conducting these control reactions to illustrate the mechanism through which electron transfer occurs in a biphasic reaction medium, three miniemulsion polymerization reactions were conducted as summarized in Table 8. The first polymerization was conducted utilizing a potential past the cathodic peak to ensure efficient and rapid reduction of CuII/TPMA to CuI/TPMA. The polymer obtained after 10 h reaction displayed a high molecular weight and a relatively broad Mw/Mn. The uncontrolled behavior of this system was attributed to the large reducing potential applied to the polymerization. Therefore, a second polymerization was conducted with a lower applied potential, entry 3. Similar to the first polymerization the resulting polymer exhibited a higher molecular weight with a broad Mw/Mn. Owing to the fact that CuI/TPMA can react with EBiB and to demonstrate that CuII/BPMODA is required to obtain any level of control a third polymerization was conducted without addition of BPMODA (entry 2). This polymerization resulted in preparation of a polymer with a very high value for Mw/Mn, reaching a value of 14. The results exemplify the profound effect of having a hydrophobic ligand (BPMODA) present in the system.
Most importantly the results indicate that the presence of both a hydrophilic and a hydrophobic ligand provides an e(ATRP) emulsion system and leads to the conclusion that development of a more active hydrophobic ligand, such as an AlkMe5TREN ligand, which would allow lower temperature miniemulsions to be conducted and be well suited for eATRP in miniemulsion systems. Such an active hydrophobic catalyst complex could, indeed should, function with a less active hydrophilic ligand, such as 2,2-bipyridene, that would not act to reduce the concentration of the catalyst in the dispersed phase. Improved control would result if the less reactive catalyst resides predominately in the aqueous phase otherwise lower concentrations of XCuII/L will be retained in the oil phase and if there in no deactivator, there is no control. So preferentially one should either match the reactivity of both hydrophilic and hydrophobic catalyst complexes and/or put the less reactive complex in the aqueous phase.
In one embodiment of the invention control of an emulsion polymerization is attained by addition of a hydrophilic ligand and a hydrophobic ligand.
Example 10
Galvanostatic eATRP
Galvanostatic conditions are attractive from an industrial standpoint because they allow the elimination of the reference electrode.
Reaction conditions: [BA]/[EBiB]/[TPMA]/[CuIITrf2]/[TPMA]/[TBABr]=300/1/0.9/0.9/0.9, [BA]=3.9 M, [TBAClO4] 0.2 M, T=44° C. The current profile shown in FIG. 24A was obtained at an Eapp 80 mV more negative than the cathodic peak potential (Epc). This profile was used to determine the appropriate currents for the galvanostatic polymerization. This current profile was divided up into two main regimes: (1) initial reduction of CuII to CuI and (2) maintenance of the current to compensate for termination events during polymerization. The area under the current profile was calculated to determine the total charged passed in each regime, afterward this value was divided by the desired time of that regime (i.e. this is an average current). Two current values were determine as shown in FIG. 24A and applied to begin polymerization. The potential at the working electrode was monitored as the polymerization proceeded, as shown in FIG. 24B. As the polymerization took place the E remained in close proximity to the CuII/CuI couple, however, near the end of each current stage it began to shift to more negative potentials. This indicates that in the vicinity of the electrode, nearly all CuII was converted to CuI, and therefore the potentiostate began to apply a stronger reducing potential to maintain these current values. The resulting polymerization results are shown in FIGS. 25(A & B). The rate of polymerization was slower in comparison to the potentiostatic experiment simply because of a smaller applied current. In regard to polymerization control, the polymerization displayed a linear increase in molecular weight with conversion and low Mw/Mn values during the course of the polymerization confirming that galvanostatic eATRP are possible.
Example 11
Copper Removal and Catalyst Regeneration in an eATRP
11A. As discussed above in section 4E, one of the significant advantages of eATRP is the ability to remove then recycle the transition metal from the polymerization medium. Therefore a variety of different potentials were applied to either deposit Cu on the Pt working electrode, or strip the bound copper from the working electrode, and/or promote polymerization of BA. Reaction conditions: [BA]/[BiB]/[TPMA]/[CuIITrf2]/[TPMA]/[TBABr]=300/1/0.03/0.03/0.03, [BA]=3.9 M, [TBAClO4] 0.2 M, T=45° C. 100 ppm catalyst was used in this polymerization. FIG. 26 shows that with a sufficiently negative potential that Cu0 deposition is possible. FIG. 27A shows that the reaction rate slows when this process is occurring, between 1.5 and 2.45 h and increases again when the potential is changed to reform CuII seen after 3 h in FIG. 27A. Chain end functionality is not affected by this reduction in concentration of catalyst and continues to increase in a regular manner throughout the reaction, FIG. 27B.
11B. Initial reaction conditions: [BA]/[EBiB]/[TPMA]/[CuIITrf2]/[TBABr]=300/1/0.09/0.09/0.09, [BA]=3.9 M, [TBAClO4]0.2 M, T=60° C. 300 ppm catalyst was in this polymerization. After 1.5. hr conversion was 72%, see Table 9, the temperature of the reactor was increased to 60° C, an applied potential was adjusted to be past that of the Cu0 deposition peak was applied. The current profile shows a decrease in the current indicating the depletion of Cu in the reaction medium. The process is rather slow and required nearly 9 h for the current to reach nominal values. A UV-V is calibration curve was generated so that the concentration of copper could be determined before and after the deposition and the resulting concentration of copper can be seen in Table 9. This process resulted in nearly 85% of the Cu being removed from the reaction vessel. There was visual confirmation of the copper deposition on the platinum electrode.







TABLE 9







Summary of polymer characterization and copper


concentration before and after electrodeposition.













time
Conversion


[Cu]



(h)
(%)
Mn
Mn/Mw
(mM)
















polymerization
1.5
72.0
28,000
1.09
1.15


deposition #1
1.5
80.1
28,300
1.09
0.78


deposition #2
14
96.9
28,600
1.12
0.18









In one embodiment of the invention the reaction is initially exposed to a larger potential to quickly generate the desired concentration of CuIBr and then the applied potential is lowered to maintain the [CuIBr] at a lower constant level thereby providing a lower concentration of propagating radicals to generate a reduced fraction of terminated chains.
Another embodiment allows the synthesis of well-controlled polymers using a low amount of catalyst by using electrochemistry to directly reduce a targeted fraction of the X-MtX+1 deactivator to the MtX activator, exemplified in these initial examples by a X-CuII deactivator and CuI activator.
In another embodiment of the invention the polymerization reaction can be started and stopped by changing the potential applied to the reaction medium. This is a convenient procedure for controlling any exotherm in a polymerization reaction by incorporating a feedback loop into the electrochemical control process.
In a further embodiment the rate of polymerization can be controlled through the magnitude of the voltage applied to the system.
The embodiments disclosed herein can be summarized as, but are not limited to, allowing
dynamic modulation of polymerization rates through electrochemical means, allowing “on demand” polymerization initiation, cessation, and rejuvenation of a controlled/living radical polymerization process thereby providing an enhanced level of polymerization control through an external potential source, i.e. potentiostat, affording complete kinetic control by the magnitude of Eapp. The disclosed procedure can additionally offer adjustable “dials”, e.g. current, potential, and total charge passed, to manipulate/control polymerization activation/deactivation, polymerization rates, and selective targeting of electro-active species which thereby affords complete kinetic control by the magnitude of applied potential, without addition of chemical reducing agents, at low catalyst concentrations.

## Claims

1. A polymerization process, comprising:
polymerizing free radically (co)polymerizable monomers in the presence of a polymerization medium initially comprising:
at least one transition metal catalyst that can participate in a redox reaction; and
an initiator comprising one or more redox transferable atoms or groups;
wherein a selected molar ratio of two oxidation states of the transition metal catalyst is directly adjusted, controlled, and/or maintained by electrochemistry throughout a time that an active polymerization is desired;
wherein the polymerization takes place in an electrolysis apparatus comprising at least a cathode and an anode;

wherein electrolysis is controlled by controlling one or more of an applied voltage, a current, and a charge passed, and
wherein the electrolysis control is selected to provide a concentration greater than or equal to 0.1% of each oxidation state of the at least one transition metal catalyst based on total transition metal added in the polymerization medium.

2. The polymerization process of claim 1, wherein a rate of polymerization is controlled through the magnitude of one or more of the applied voltage, the current, and the charge passed.

3. The process of claim 2, wherein the molar ratio of the two oxidation states of the transition metal catalyst at a specific time in the polymerization is determined by the one or more of the applied voltage, the current, and the charge passed through the polymerization medium and current values.

4. The process of claim 2, wherein the molar ratio of a higher oxidation state transition metal catalyst and a lower oxidation state transition metal catalyst are adjusted through the magnitude of the applied voltage or the current applied to the polymerization medium to control the polymerization of the free radically (co)polymerizable monomers with the at least one transition metal catalyst and one or more ligands.

5. The process of claim 1, wherein the electrochemistry can be started and stopped by changing the applied voltage or the current, or switching the applied voltage or the current “on” or “off”, optionally where the applied voltage or the current is capable of controlling a reaction exotherm.

6. The process of claim 1, wherein the concentration of the at least one transition metal catalyst in the polymerization medium is less than 1000 ppm.

7. The process of claim 1, wherein the at least one transition metal catalyst comprises one or more ligands forming a transition metal catalyst complex;
wherein the one or more ligands controls the solubility and activity of the transition metal catalyst complex in the polymerization medium.

8. The process of claim 7, wherein the transition metal catalyst complex comprises two different ligands.

9. The process of claim 7, wherein the electrochemistry is adjusted, controlled, and/or maintained by applying the applied voltage to the polymerization medium, wherein the applied voltage is based on an E1/2 value, as determined by cyclic voltammetry, of the transition metal catalyst complex.

10. The process of claim 9, wherein the applied voltage is based on the E1/2 value, as determined by the cyclic voltammetry, of the at least one transition metal catalyst, the one or more ligands, the monomers, and optionally a solvent in the polymerization medium.

11. The process of claim 10, wherein the applied voltage is based on the E1/2 value, as determined by the cyclic voltammetry, of the at least one transition metal catalyst, the one or more ligands, the monomers, the initiator, and the optional solvent in the polymerization medium.

12. The process of claim 7, wherein the electrochemistry is adjusted, controlled, and/or maintained by applying the applied voltage to the polymerization medium, wherein the applied voltage is based on an E1/2 value, as determined by cyclic voltammetry, of the at least one transition metal catalyst, one or more ligands, the monomers, and optionally an electrolyte in the polymerization medium.

13. The process of claim 12, wherein the applied voltage is based on the E1/2 value, as determined by the cyclic voltammetry, of the at least one transition metal catalyst, the one or more ligands, the monomers, the initiator, and the optional electrolyte in the polymerization medium.

14. The process of claim 1, wherein the at least one transition metal catalyst comprises two different transition metals.

15. The process of claim 1, wherein the concentration of the at least one transition metal catalyst in the polymerization medium is reduced by electrodeposition of the at least one transition metal catalyst on the cathode of the electrolysis apparatus.

16. The process of claim 1, wherein a transition metal catalyst complex is formed in-situ directly from a reaction of a solid transition metal deposited on the cathode with one or more ligands in the polymerization medium.

17. The process of claim 1, wherein the polymerization medium is a medium selected from the group consisting of an organic medium, an aqueous medium and a biphasic medium.

18. The process of claim 1, wherein the electrochemistry is adjusted by one or more of the applied voltage and the current at one or more times during the polymerization process.

19. The process of claim 1, wherein the polymerization medium further comprises an electrolyte.

20. The process of claim 19, wherein the electrochemistry is adjusted by the applied voltage and the current to retain at least 0.1% concentration of both an activator state of the at least one transition metal catalyst and a deactivator state of the at least one transition metal catalyst in the polymerization medium throughout the time that the active polymerization is desired.

21. The process of claim 19, wherein the electrolyte comprises a same counterion present on a first added transition metal salt that forms the at least one transition metal catalyst.

22. The process of claim 19, wherein the electrolyte comprises a different counterion from that present on a first added transition metal salt that forms the at least one transition metal catalyst.

23. The process of claim 22, wherein the electrolyte further comprises a quaternary ammonium complex or a triflate.