Polymers with antimicrobial functionalities

Techniques regarding polymers with antimicrobial functionality are provided. For example, one or more embodiments described herein can regard a polymer, which can comprise a repeating ionene unit. The repeating ionene unit can comprise a cation distributed along a degradable backbone. The degradable backbone can comprise a terephthalamide structure. Further, the repeating ionene unit can have antimicrobial functionality.

BACKGROUND

The subject disclosure relates to one or more polymers with antimicrobial functionalities, and more specifically, to one or more polyionenes comprising cations and/or hydrophobic functional groups distributed along a degradable backbone.

SUMMARY

According to an embodiment, a polymer is provided. The polymer can comprise a repeating ionene unit. The repeating ionene unit can comprise a cation distributed along a degradable backbone. The degradable backbone can comprise a terephthalamide structure. Further, the repeating ionene unit can have antimicrobial functionality.

According to an embodiment, a method is provided. The method can comprise dissolving a plurality of amine monomers with an electrophile in a solvent. The plurality of amine monomers can comprise a degradable backbone, which can comprise a terephthalamide structure. The method can also comprise polymerizing the plurality of amine monomers and the electrophile to form a repeating ionene unit. The repeating ionene unit can comprise a cation located along the degradable backbone. Also, the repeating ionene unit can have antimicrobial functionality.

According to an embodiment, a polyionene composition is provided. The polyionene composition can comprise a repeating ionene unit. The repeating ionene unit can comprise a degradable molecular backbone, which can comprise a terephthalamide structure. The repeating ionene unit can also comprise a cation covalently bonded to the degradable molecular backbone. Further, the repeating ionene unit can have antimicrobial functionality.

According to an embodiment, a method is provided. The method can comprise dissolving a plurality of degradable amine monomers with an electrophile in a solvent. The method can also comprise polymerizing the plurality of degradable amine monomers and the electrophile to form a precipitate. The precipitate can comprise a repeating ionene unit, which can comprise a cation distributed along a degradable molecular backbone. The degradable molecular backbone can comprise a terephthalamide structure. Also, the repeating ionene unit can have antimicrobial functionality.

According to an embodiment, a method is provided. The method can comprise contacting a pathogen with a polymer. The polymer can comprise a repeating ionene unit, which can comprise a cation distributed along a degradable backbone. The degradable backbone can comprise a terephthalamide structure. Also, the repeating ionene unit can have antimicrobial functionality.

DETAILED DESCRIPTION

The discovery and refinement of antibiotics was one of the crowning achievements in the 20thcentury that revolutionized healthcare treatment. For example, antibiotics such as penicillin, ciprofloxacin and, doxycycline can achieve microbial selectivity through targeting and disruption of a specific prokaryotic metabolism, while concurrently, remaining benign toward eukaryotic cells to afford high selectivity. If properly dosed, they could eradicate infection. Unfortunately, this therapeutic specificity of antibiotics also leads to their undoing as under-dosing (incomplete kill) allows for minor mutative changes that mitigate the effect of the antibiotic leading to resistance development. Consequently, nosocomial infections, caused by medication-resistant microbes such as methicillin-resistantStaphylococcus aureus(MRSA), multi-medication-resistantPseudomonas aeruginosaand vancomycin-resistantEnterococci(VRE) have become more prevalent. An added complexity is the pervasive use of antimicrobial agents in self-care products, sanitizers and hospital cleaners etc, including anilide, bis-phenols, biguanides and quaternary ammonium compounds, where a major concern is the development of cross- and co-resistance with clinically used antibiotics, especially in a hospital setting. Another unfortunate feature with triclosan, for example, is its cumulative and persistent effects in the skin. Moreover, biofilms have been associated with numerous nosocomial infections and implant failure, yet the eradication of biofilms is an unmet challenge to this date. Since antibiotics are not able to penetrate through extracellular polymeric substance that encapsulates bacteria in the biofilm, further complexities exist that lead to the development of medication resistance.

However, polymers having a cationic charge can provide electrostatic disruption of the bacterial membrane interaction. Furthermore, cationic polymers are readily made amphiphilic with addition of hydrophobic regions permitting both membrane association and integration/lysis. The amphiphilic balance has shown to play an important effect not only in the antimicrobial properties but also in the hemolytic activity. Many of these antimicrobial polymers show relatively low selectivity as defined by the relative toxicity to mammalian cells or hemolysis relative to pathogens.

As used herein, the term “ionene” can refer to a polymer unit, a copolymer unit, and/or a monomer unit that can comprise a nitrogen cation and/or a phosphorus cation distributed along, and/or located within, a molecular backbone, thereby providing a positive charge. Example nitrogen cations include, but are not limited to: quaternary ammonium cations, protonated secondary amine cations, protonated tertiary amine cations, and/or imidazolium cations. Example, phosphorus cations include, but are not limited to: quaternary phosphonium cations, protonated secondary phosphine cations, and protonated tertiary phosphine cations. As used herein, the term “molecular backbone” can refer to a central chain of covalently bonded atoms that form the primary structure of a molecule. In various embodiments described herein, side chains can be formed by bonding one or more functional groups to a molecular backbone. As used herein, the term “polyionene” can refer to a polymer that can comprise a plurality of ionenes. For example, a polyionene can comprise a repeating ionene.

FIG. 1Aillustrates a diagram of an example, non-limiting ionene unit100in accordance with one or more embodiments described herein. The ionene unit100can comprise a molecular backbone102, one or more cations104, and/or one or more hydrophobic functional groups106. In various embodiments, an ionene and/or a polyionene described herein can comprise the ionene unit100. For example, a polyionene described herein can comprise a plurality of ionenes bonded together, wherein the bonded ionenes can have a composition exemplified by ionene unit100.

The molecular backbone102can comprise a plurality of covalently bonded atoms (illustrated as circles inFIGS. 1A and 1B). The atoms can be bonded in any desirable formation, including, but not limited to: chain formations, ring formations, and/or a combination thereof. The molecular backbone102can comprise one or more chemical structures including, but not limited to: alkyl structures, aryl structures, alkane structures, aldehyde structures, ester structures, carboxyl structures, carbonyl structures, amine structures, amide structures, phosphide structures, phosphine structures, a combination thereof, and/or the like. One of ordinary skill in the art will recognize that the number of atoms that can comprise the molecular backbone can vary depending of the desired function of the ionene unit100. For example, while nineteen atoms are illustrated inFIG. 1A, a molecular backbone102that can comprise dozens, hundreds, and/or thousands of atoms is also envisaged.

Located within the molecular backbone102are one or more cations104. As described above, the one or more cations104can comprise nitrogen cations and/or phosphorous cations. The cations104can be distributed along the molecular backbone102, covalently bonded to other atoms within the molecular backbone102. In various embodiments, the one or more cations104can comprise at least a portion of the molecular backbone102. One of ordinary skill in the art will recognize that the number of a cations104that can comprise the ionene unit100can vary depending of the desired function of the ionene unit100. For example, while two cations104are illustrated inFIG. 1A, an ionene unit100that can comprise dozens, hundreds, and/or thousands of cations104is also envisaged. Further, whileFIG. 1Aillustrates a plurality of cations104evenly spaced apart, other configurations wherein the cations104are not evenly spaced apart are also envisaged. Also, the one or more cations104can be located at respective ends of the molecular backbone102and/or at intermediate portions of the molecular backbone102, between two or more ends of the molecular backbone102. The one or more cations104can provide a positive charge to one or more locations of the ionene unit100.

The one or more hydrophobic functional groups106can be bonded to the molecular backbone102to form a side chain. The one or more of the hydrophobic functional groups106can be attached to the molecular backbone102via bonding with a cation104. Additionally, one or more hydrophobic functional groups106can be bonded to an electrically neutral atom of the molecular backbone102. The ionene unit100can comprise one or more hydrophobic functional groups106bonded to: one or more ends of the molecular backbone102, all ends of the molecular backbone102, an intermediate portion (e.g., a portion between two ends) of the molecular backbone102, and/or a combination thereof.

While a biphenyl group is illustrated inFIG. 1Aas the hydrophobic functional group106, other functional groups that are hydrophobic are also envisaged. Example, hydrophobic functional groups106can include, but are not limited to: alkyl structures, aryl structures, alkane structures, aldehyde structures, ester structures, carboxyl structures, carbonyl structures, carbonate structures, alcohol structures, a combination thereof, and/or the like. In various embodiments, the one or more hydrophobic functional groups106can comprise the same structure. In other embodiments, one or more of the hydrophobic functional groups106can comprise a first structure and one or more other hydrophobic functional groups106can comprise another structure.

FIG. 1Billustrates a diagram of an example, non-limiting lysis process108that can be facilitated by the ionene unit100in accordance with one or more embodiments described herein. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity. The lysis process108can comprise a plurality of stages, which can collectively comprise an attack mechanism that can be performed by the ionene unit100against a pathogen cell. Example pathogen cells can include, but are not limited to: Gram-positive bacteria cells, Gram-negative bacteria cells, fungi cells, and/or yeast cells.

The target pathogen cell can comprise a membrane having a phospholipid bilayer110. In various embodiments, the membrane can be an extracellular matrix. The phospholipid bilayer110can comprise a plurality of membrane molecules112covalently bonded together, and the membrane molecules112can comprise a hydrophilic head114and one or more hydrophobic tails116. Further, one or more of the plurality of membrane molecules112can be negatively charged (as illustrated inFIG. 1Bwith a “−” symbol).

At118, electrostatic interaction can occur between the positively charged cations104of the ionene unit100and one or more negatively charged membrane molecules112. For example, the negative charge of one or more membrane molecules112can attract the ionene unit100towards the membrane (e.g., the phospholipid bilayer110). Also, the electrostatic interaction can electrostatically disrupt the integrity of the membrane (e.g., phospholipid bilayer110). Once the ionene unit100has been attracted to the membrane (e.g., phospholipid bilayer110), hydrophobic membrane integration can occur at120. For example, at120one or more hydrophobic functional groups106of the ionene unit100can begin to integrate themselves into the phospholipid bilayer110. While the positively charged portions of the ionene unit100are attracted, and electrostatically disrupting, one or more negatively charged membrane molecules112(e.g., one or more hydrophilic heads114), the one or more hydrophobic functional groups106can insert themselves between the hydrophilic heads114to enter a hydrophobic region created by the plurality of hydrophobic tails116.

As a result of the mechanisms occurring at118and/or120, destabilization of the membrane (e.g., the phospholipid bilayer110) can occur at122. For example, the one or more hydrophobic functional groups106can serve to cleave one or more negatively charged membrane molecules112from adjacent membrane molecules112, and the positively charged ionene unit100can move the cleaved membrane segment (e.g., that can comprise one or more negatively charged membrane molecules112and/or one or more neutral membrane molecules112constituting a layer of the phospholipid bilayer110) away from adjacent segments of the membrane (e.g., adjacent segments of the phospholipid bilayer110). As cleaved segments of the membrane (e.g., the phospholipid bilayer110) are pulled away, they can fully detach from other membrane molecules112at124, thereby forming gaps in the membrane (e.g., the phospholipid bilayer110). The formed gaps can contribute to lysis of the subject pathogen cell. In various embodiments, a plurality of ionene units100can perform the lysis process108on a cell simultaneously. Furthermore, the ionene units100participating in a lysis process108need not perform the same stages of the attack mechanism at the same time.

FIG. 2illustrates a diagram of an example, non-limiting chemical formula200that can characterize the structure of a repeating ionene unit100in accordance with one or more embodiments described herein. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity. In various embodiments, the repeating ionene units100characterized by chemical formula200can be covalently bonded together to form a polymer (e.g., a polyionene composition).

As shown inFIG. 2, a repeating ionene unit100characterized by chemical formula200can comprise a degradable molecular backbone102. Further, the degradable molecular backbone102can comprise one or more terephthalamide structures. In various embodiments, the repeating ionene unit100characterized by chemical formula200can be derived from polyethylene terephthalate (PET), wherein the one or more terephthalamide structures can be derived from the PET. However, one or more embodiments of chemical formula200can comprise a terephthalamide structure derived from one or more molecules other than PET.

The “X” inFIG. 2can represent the one or more cations104. For example, “X” can represent one or more cations104selected from a group that can include, but is not limited to: one or more nitrogen cations, one or more phosphorus cations, and/or a combination thereof. For instance, “X” can represent one or more nitrogen cations selected from a group that can include, but is not limited to: one or more protonated secondary amine cations, one or more protonated tertiary amine cations, one or more quaternary ammonium cations, one or more imidazolium cations, and/or a combination thereof. In another instance, “X” can represent one or more phosphorus cations selected from a group that can include, but is not limited to: one or more protonated secondary phosphine cations, one or more protonated tertiary phosphine cations, one or more quaternary phosphonium cations, and/or a combination thereof.

The one or more cations104(e.g., represented by “X” in chemical formula200) can be covalently bonded to one or more linkage groups to form, at least a portion, of the degradable molecular backbone102. The one or more linkage groups can link the one or more cations104to the one or more terephthalamide structures, thereby comprising the molecular backbone102. The “Y” inFIG. 2can represent the one or more linkage groups. The one or more linkage groups can comprise any structure in compliance with the various features of the molecular backbone102described herein. For example, the one or more linkage groups can have any desirable formation, including, but not limited to: chain formations, ring formations, and/or a combination thereof. The one or more linkage groups can comprise one or more chemical structures including, but not limited to: alkyl structures, aryl structures, alkane structures, aldehyde structures, ester structures, carboxyl structures, carbonyl structures, a combination thereof, and/or the like. For instance, “Y” can represent one or more linkage groups that can comprise an alkyl chain having greater than or equal to two carbon atoms and less than or equal to 15 carbon atoms.

As shown inFIG. 2, in various embodiments, a repeating ionene unit100characterized by chemical formula200can comprise cations104(e.g., represented by “X”) at a plurality of locations along the molecular backbone102. For example, cations104can be located at either end of the molecular backbone102(e.g., as illustrated inFIG. 2). However, in one or more embodiments of chemical formula200, the molecular backbone102can comprise less or more cations104than the two illustrated inFIG. 2.

Further, the “R” shown inFIG. 2can represent the one or more hydrophobic functional groups106in accordance with the various embodiments described herein. For example, the one or more hydrophobic functional groups106can comprise one or more alkyl groups and/or one or more aryl groups. For instance, the hydrophobic functional group106can be derived from a dialkyl halide. The one or more hydrophobic functional groups106(e.g., represented by “R” inFIG. 2) can be covalently bonded to one or more of the cations104(e.g., represented by “X” inFIG. 2) and/or the molecular backbone102, which can comprise the one or more cations104(e.g., represented by “X” inFIG. 2), one or more linkage groups (e.g., represented by “Y” inFIG. 2), and/or one or more terephthalamide structures. In addition, the “n” shown inFIG. 2can represent an integer greater than or equal to two and less than or equal to one thousand.

FIG. 3illustrates a flow diagram of an example, non-limiting method300that can facilitate generating one or more repeating ionene units100that can be characterized by chemical formula200. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity.

At302, the method300can comprise dissolving a plurality of amine monomers with one or more electrophiles in a solvent. The plurality of amine monomers can comprise a degradable backbone. Further, the degradable backbone can comprise one or more terephthalamide structures. Additionally, the plurality of amine monomers can further comprise a structure selected from a group that can include, but is not limited to: alkyl amine groups, hetero cyclic amine groups, a combination thereof, and/or the like. Moreover, in one or more embodiments the plurality of degradable amine monomers can be degradable tetra-amine monomers.

The one or more electrophiles can comprise, for example, one or more alkyl halides (e.g., dialkyl halides). For instance, the one or more electrophiles can comprise one or more dialkyl halides having chloride and/or bromide. Example electrophiles can include, but are not are not limited to: p-xylylene dichloride, 4,4′-bis(chloromethyl)biphenyl, 1,4-bis(bromomethyl)benzene, 4,4′-bis(bromomethyl)biphenyl, a combination thereof, and/or the like. The solvent can be an organic solvent. Example solvents can include but are not limited to: dimethyl formamide (“DMF”), 1,8-diazabicyclo[5.4.0]undec-7-ene (“DBU”), 1-(3,5-bis(trifluoromethyl)-phenyl)-3-cyclohexyl-2-thiourea (“TU”), and/or a combination thereof, and/or the like.

At304, the method300can comprise polymerizing the plurality of amine monomers and the one or more electrophiles to form a repeating ionene unit (e.g., ionene unit100). The repeating ionene unit (e.g., ionene unit100) can comprise a cation104(e.g., a nitrogen cation and/or a phosphorus cation) located along the degradable backbone (e.g., a molecular backbone102). Further, the repeating ionene unit100can have antimicrobial functionality.

During the polymerization at304, a nitrogen atom and/or a phosphorus atom located in the degradable backbone can be subject to alkylation and/or quaternization; thus, the polymerization at304can conduct a polymer-forming reaction (e.g., formation of the repeating ionene unit100) and an installation of charge (e.g., forming a cation104, including a nitrogen cation and/or a phosphorus cation) simultaneously without a need of a catalyst. Further, one or more hydrophobic functional groups106can be derived from the one or more electrophiles and/or can be bonded to the one or more cations104as a result of the alkylation and/or quaternization process.

The repeating ionene unit formed at304can comprise one or more embodiments of the ionene unit100and can be characterized by one or more embodiments of chemical formula200. For instance, the repeating ionene unit100formed at304can comprise a degradable molecular backbone102that can comprise one or more cations104(e.g., represented by “X” in chemical formula200), one or more linkage groups (e.g., represented by “Y” in chemical formula200), a terephthalamide structure (e.g., as shown inFIG. 2), and/or one or more hydrophobic functional groups106(e.g., represented by “R” in chemical formula200). The one or more cations104can be nitrogen cations (e.g., quaternary ammonium cations, imidazolium cations, and/or a combination thereof) and/or phosphorus cations (e.g., quaternary phosphonium cations). The cations104can be linked to the terephthalamide structure via one or more linkage groups (e.g., alkyl groups and/or aryl groups). Further, one or more of the cations104can be bonded to one or more of the hydrophobic functional groups106. Additionally, the repeating ionene unit100formed at304can repeat a number of times greater than or equal to 2 and less than or equal to 1000.

FIG. 4illustrates another flow diagram of an example, non-limiting method400that can be practiced in accordance with the one or more embodiments of method300and can generate repeating ionene units100, which can be characterized by chemical formula200. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity.

At402, the method400can comprise dissolving a plurality of degradable amine monomers with one or more electrophiles in a solvent. As described above regarding method300, the plurality of degradable amine monomers can further comprise a structure selected from a group that can include, but is not limited to: alkyl amine groups, hetero cyclic amine groups, a combination thereof, and/or the like. Moreover, in one or more embodiments the plurality of degradable amine monomers can be degradable tetra-amine monomers.

The one or more electrophiles can comprise, for example, one or more alkyl halides (e.g., dialkyl halides). For instance, the one or more electrophiles can comprise one or more dialkyl halides having chloride and/or bromide. Example electrophiles can include, but are not are not limited to: p-xylylene dichloride, 4,4′-bis(chloromethyl)biphenyl, 1,4-bis(bromomethyl)benzene, 4,4′-bis(bromomethyl)biphenyl, a combination thereof, and/or the like.

The solvent can be an organic solvent. Example solvents can include but are not limited to: DMF, DBU, TU, and/or a combination thereof, and/or the like. For example, DMF can be used as the solvent as it can dissolve the reactants at elevated temperatures. In one or more embodiments, equimolar amounts of the plurality of degradable amine monomers and the one or more electrophiles can be dissolved in the solvent.

In one or more embodiments, the plurality of degradable amine monomers can be prepared through an aminolysis of PET. For example, PET can be depolymerized with one or more aminolysis reagents. The one or more aminolysis reagents can be diamines. A first amino group of the diamines can include, but are not limited to, a primary amino group and a secondary amino group. Also, a second amino group of the diamines can include, but are not limited to: a primary amino group, a secondary amino group, a tertiary amino group, and/or an imidazole group. For example, in one or more embodiments the secondary amino group is a tertiary amino group and/or an imidazole group.

Scheme 1, presented below, demonstrates three exemplary, non-liming degradable amine monomers that can be prepared through aminolysis of PET.

Preparation of the plurality of degradable amine monomers (e.g., in accordance with Scheme 1) can be performed without the need of a catalyst and/or a solvent. Further, aminolysis of PET can be performed with an excess of the aminolysis reagents (e.g., four times excess of the aminolysis reagents). Moreover, the aminolysis can depolymerize PET at elevated temperatures. Upon cooling, the target degradable amine monomers can be crystallized from the excess reagent and an alcohol side product (e.g., ethylene glycol). The degradable amine monomers can then be filtered, rinsed (e.g., with ethylacetate), and used without need for further purification.

While Scheme 1 depicts three example degradable amine monomers derived from PET, other degradable amine monomers that can be derived from PET are also envisaged. For example, PET can be depolymerized with aminolysis reagents other than the three depicted in Scheme 1. For instance, any aminolysis reagent having a primary amino group and/or a secondary amino group, which can donate a hydrogen atom to facilitate bonding to the terephthalate structure, and a second amino group and/or imidazole group, which can later become a cation104, can be polymerized with PET to prepare a degradable amine monomer for use at402. Further, the prepared degradable amine monomers derived from PET, as described herein, can comprise the plurality of amine monomers that can be utilized in method300.

Additionally, in one or more embodiments the plurality of degradable amine monomers utilized in conjunction with the methods described herein (e.g., method300and/or method400) can be derived from a molecule other than PET. One of ordinary skill in the art can readily recognize that a plethora of other starting molecules can be polymerized and/or depolymerized to prepare the plurality of amine monomers (e.g., which can have degradable backbones, can comprise a terephthalamide structure, and/or can be a tetra-amine) that can be utilized in conjunction with the methods described herein (e.g., method300and/or method400).

At404, the method400can optionally comprise stirring the plurality of degradable amine monomers, the one or more electrophiles, and the solvent at a temperature greater than or equal to 15 degrees Celsius (° C.) and less than or equal to 150° C. for a period of time greater than or equal to 8 hours and less than or equal to 72 hours (e.g., greater than or equal to 12 hours and less than or equal to 24 hours).

At406, the method400can comprise polymerizing the plurality of degradable amine monomers and the electrophile to form a precipitate (e.g., a polyionene composition). The precipitate (e.g., a polyionene composition) can comprise a repeating ionene unit100(e.g., characterized by chemical formula200) that can comprise a cation104distributed along a degradable molecular backbone102. The molecular backbone102can comprise a terephthalamide structure (e.g., as illustrated in chemical formula200). Further, the repeating ionene unit100formed at406can have antimicrobial functionality. In one or more embodiments, the polymerizing at406can be performed under nitrogen gas. Additionally, the polymerizing at406can generate the cation through alkylation and/or quaternation with the one or more electrophiles. In various embodiments, the terephthalamide structure comprising the precipitate can be derived from the PET that was depolymerized to prepare a plurality of degradable amine monomers.

During the polymerization at406, a nitrogen atom and/or a phosphorus atom located in the degradable amine monomers can be subject to alkylation and/or quaternization; thus, the polymerization at406can conduct a polymer-forming reaction (e.g., formation of the repeating ionene unit100) and an installation of charge (e.g., forming a cation104, including a nitrogen cation and/or a phosphorus cation) simultaneously without a need of a catalyst. Further, one or more hydrophobic functional groups106can be derived from the one or more electrophiles and/or can be bonded to the one or more cations104as a result of the alkylation and/or quaternization process.

For example, the repeating ionene formed at406can comprise one or more embodiments of the ionene unit100and can be characterized by one or more embodiments of chemical formula200. For instance, the repeating ionene unit100formed at406can comprise a degradable molecular backbone102that can comprise one or more cations104(e.g., represented by “X” in chemical formula200), one or more linkage groups (e.g., represented by “Y” in chemical formula200), a terephthalamide structure (e.g., as shown inFIG. 2), and/or one or more hydrophobic functional groups106(e.g., represented by “R” in chemical formula200). The one or more cations104can be nitrogen cations (e.g., quaternary ammonium cations, imidazolium cations, and/or a combination thereof) and/or phosphorus cations (e.g., quaternary phosphonium cations). The cations104can be linked to the terephthalamide structure via one or more linkage groups (e.g., alkyl groups and/or aryl groups). Further, one or more of the cations104can be bonded to one or more of the hydrophobic functional groups106. Additionally, the repeating ionene unit100formed at406can repeat a number of times greater than or equal to 2 and less than or equal to 1000.

Antimicrobial activity of the repeating ionene units100generated by the methods described herein (e.g., method300and/or method400) can be independent of molecular weight. Thus, the methods (e.g., method300and/or method400) can target polymerization conditions that can extinguish molecular weight attainment by diffusion limited mechanism (e.g., polymer precipitation) to modest molecular weights (e.g., molecular weights less than 10,000 grams per mole (g/mol)), which can aid in the solubility of the repeating ionene units100in aqueous media.

FIG. 5illustrates a diagram of an example, non-limiting scheme500that can depict the polymerization of one or more repeating ionene units100(e.g., characterized by chemical formula200) in accordance with one or more of the methods (e.g., method300and/or method400) described herein. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity. For example, scheme500can depict a first polymerization that can form a first polyionene composition502(e.g., a repeating ionene unit100that can be characterized by chemical formula200and/or generated by method300and/or method400). Scheme500can also depict a second polymerization that can form a second polyionene composition504(e.g., a repeating ionene unit100that can be characterized by chemical formula200and/or generated by method300and/or method400). In scheme500, “n” can represent an integer greater than or equal to two and less than or equal to one thousand. Additionally, the first monomer reactant501utilized in the first polymerization and the second polymerization can be a degradable tetra-amine monomer comprising a terephthalamide structure that can be derived from PET in accordance with the various embodiments described herein (e.g., Scheme 1). In one or more other embodiments, the amine monomer reactant501can be derived from a molecular other than PET.

The first polymerization can form the first polyionene composition502by polymerizing the first monomer reactant501(e.g., derived from aminolysis of PET) with p-xylylene dichloride. The first polymerization can simultaneously form the structure of the first polyionene composition502and positively charge the first polyionene composition502(e.g., by generating the plurality of quaternary ammonium cations) through quaternization of the first monomer reactant's501tertiary amino groups distributed along the first monomer reactant's501degradable backbone (e.g., molecular backbone102).

The second polymerization can form the second polyionene composition504by polymerizing the first monomer reactant501(e.g., derived from aminolysis of PET) with 4,4′-bis(chloromethyl)-1,1′-biphenyl. The second polymerization can simultaneously form the structure of the second polyionene composition504and positively charge the second polyionene composition504(e.g., by generating the plurality of quaternary ammonium cations) through quaternization of the first monomer reactant's501tertiary amino groups distributed along the first monomer reactant's501degradable backbone (e.g., molecular backbone102).

FIG. 6illustrates another diagram of an example, non-limiting scheme600that can depict the polymerization of one or more repeating ionene units100(e.g., characterized by chemical formula200) in accordance with one or more of the methods (e.g., method300and/or method400) described herein. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity. For example, scheme600can depict a third polymerization that can form a third polyionene composition602(e.g., a repeating ionene unit100that can be characterized by chemical formula200and/or generated by method300and/or method400). Scheme600can also depict a fourth polymerization that can form a fourth polyionene composition604(e.g., a repeating ionene unit100that can be characterized by chemical formula200and/or generated by method300and/or method400). In scheme600, “n” can represent an integer greater than or equal to two and less than or equal to one thousand. Additionally, the second monomer reactant601utilized in the third polymerization and the fourth polymerization can be a degradable tetra-amine monomer comprising a terephthalamide structure that can be derived from PET in accordance with the various embodiments described herein (e.g., Scheme 1).

The third polymerization can form the third polyionene composition602by polymerizing the second monomer reactant601(e.g., derived from aminolysis of PET) with p-xylylene dichloride. The third polymerization can simultaneously form the structure of the third polyionene composition602and positively charge the third polyionene composition602(e.g., by generating the plurality of quaternary ammonium cations) through quaternization of the second monomer reactant's601tertiary amino groups distributed along the second monomer reactant's601degradable backbone (e.g., molecular backbone102).

The fourth polymerization can form the fourth polyionene composition604by polymerizing the second monomer reactant601(e.g., derived from aminolysis of PET) with 4,4′-bis(chloromethyl)-1,1′-biphenyl. The fourth polymerization can simultaneously form the structure of the fourth polyionene composition604and positively charge the fourth polyionene composition604(e.g., by generating the plurality of quaternary ammonium cations) through quaternization of the second monomer reactant's601tertiary amino groups distributed along the second monomer reactant's601degradable backbone (e.g., molecular backbone102).

FIG. 7illustrates another diagram of an example, non-limiting scheme700that can depict the polymerization of one or more repeating ionene units100(e.g., characterized by chemical formula200) in accordance with one or more of the methods (e.g., method300and/or method400) described herein. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity. For example, scheme700can depict a fifth polymerization that can form a fifth polyionene composition702(e.g., a repeating ionene unit100that can be characterized by chemical formula200and/or generated by method300and/or method400). Scheme700can also depict a sixth polymerization that can form a sixth polyionene composition704(e.g., a repeating ionene unit100that can be characterized by chemical formula200and/or generated by method300and/or method400). In scheme700, “n” can represent an integer greater than or equal to two and less than or equal to one thousand. Additionally, the third monomer reactant701utilized in the third polymerization and the fourth polymerization can be a degradable tetra-amine monomer comprising a terephthalamide structure that can be derived from PET in accordance with the various embodiments described herein (e.g., Scheme 1).

The fifth polymerization can form the fifth polyionene composition702by polymerizing the third monomer reactant701(e.g., derived from aminolysis of PET) with p-xylylene dichloride. The fifth polymerization can simultaneously form the structure of the fifth polyionene composition702and positively charge the fifth polyionene composition702(e.g., by generating the plurality of imidazolium cations) through alkylation of the third monomer reactant's701imidazole rings distributed along the third monomer reactant's701degradable backbone (e.g., molecular backbone102).

The sixth polymerization can form the sixth polyionene composition704by polymerizing the third monomer reactant701(e.g., derived from aminolysis of PET) with 4,4′-bis(chloromethyl)-1,1′-biphenyl. The sixth polymerization can simultaneously form the structure of the sixth polyionene composition704and positively charge the sixth polyionene composition704(e.g., by generating the plurality of imidazolium cations) through alkylation of the third monomer reactant's701imidazole rings distributed along the third monomer reactant's701degradable backbone (e.g., molecular backbone102).

FIG. 8illustrates a diagram of an example, non-limiting chart800that can depict the antimicrobial efficacy of one or more polyionene compositions in accordance with one or more embodiments described herein. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity. To demonstrate the antimicrobial effects of the polyionenes described herein (e.g., repeating ionene units100that can be characterized by chemical formula200and/or generated by method300and/or method400, such as those depicted in scheme500, scheme600, and/or scheme700), a plurality of polyionene compositions were evaluated against a broad spectrum of pathogens.

The first column802of chart800can depict the polyionene composition subject to evaluation. The second column804of chart800can depict the minimum inhibitory concentration (MIC) in micrograms per milliliter (μg/mL) of the subject polyionene composition regardingStaphylococcus aureus(“SA”). The third column806of chart800can depict the MIC in μg/mL of the subject polyionene composition regardingEscherichia coli(“EC”). The fourth column808of chart800can depict the MIC in μg/mL of the subject polyionene composition regardingPseudomonas aeruginosa(“PA”). The fifth column810of chart800can depict the MIC in μg/mL of the subject polyionene composition regardingCandida albicans(“CA”). The sixth column812of chart800can depict the hemolytic activity (“HC50”) in μg/mL of the subject polyionene composition regarding rat red blood cells.

As shown in chart800, the first polyionene composition502and the second polyionene composition504can have strong antimicrobial activity with the former being more potent (e.g., having lower MIC). The second polyionene composition504can be relatively more hydrophobic than the first polyionene composition502, and thus it may interact with one or more proteins in the culture medium used to evaluate the polyionene compositions. Both the first polyionene composition502and the second polyionene composition504can cause negligible hemolysis of rat red blood cells at the effective concentrations with the polymer concentration that leads to lysis of 50% of rat red blood cells (HC50) above 2000 μg/mL. Compared to the first polyionene composition502and the second polyionene composition504, the use of imidazolium in the fifth polyionene composition702and the sixth polyionene composition704can offer similar antimicrobial potency (e.g., similar MIC ranges). However, the fifth polyionene composition702and the sixth polyionene composition704can cause higher toxicity to mammalian cells (e.g., reflected by lower HC50values).

FIG. 9illustrates a diagram of an example, non-limiting graph900that can depict the hemolytic activity of various polyionene compositions at various concentrations in accordance with the one or more embodiments described herein. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity. For example,FIG. 9shows the hemolytic activity of the first polyionene composition502, the second polyionene composition504, the fifth polyionene composition702, and/or the sixth polyionene composition704at concentrations ranging from 8 parts per million (ppm) to 2000 ppm. The hemolytic activity depicted in graph900can regard rat red blood cells.

FIG. 10illustrates another flow diagram of an example, non-limiting method1000of killing a pathogen, preventing the growth of a pathogen, and/or preventing contamination by a pathogen. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity. Example pathogens include, but are not limited to: Gram-negative bacteria, Gram-positive bacteria, fungi, yeast, a combination thereof, and/or the like.

At1002, the method1000can comprise contacting the pathogen with a polymer. The polymer can comprise a repeating ionene unit100(e.g., characterized by chemical formula200). The repeating ionene unit100can comprise a cation104(e.g., a nitrogen cation and/or a phosphorus cation) distributed along a degradable backbone (e.g., a molecular backbone102) that can comprise one or more terephthalamide structures (e.g., derived from an aminolysis of PET). The repeating ionene unit100can have antimicrobial functionality.

At1004, the method1000can comprise electrostatically disrupting a membrane of the pathogen (e.g., via lysis process108) upon contacting the pathogen with the polymer (e.g., a repeating ionene unit100characterized by chemical formula200). Additionally, contacting the pathogen with the polymer (e.g., a repeating ionene unit100characterized by chemical formula200) can disrupt the membrane through hydrophobic membrane integration (e.g., via lysis process108).

The repeating ionene unit that can comprise the polymer contacting the pathogen at1002can comprise one or more embodiments of the ionene unit100and can be characterized by one or more embodiments of chemical formula200. For instance, the repeating ionene unit100can comprise a degradable molecular backbone102that can comprise one or more cations104(e.g., represented by “X” in chemical formula200), one or more linkage groups (e.g., represented by “Y” in chemical formula200), a terephthalamide structure (e.g., as shown inFIG. 2), and/or one or more hydrophobic functional groups106(e.g., represented by “R” in chemical formula200). The one or more cations104can be nitrogen cations (e.g., quaternary ammonium cations, imidazolium cations, and/or a combination thereof) and/or phosphorus cations (e.g., quaternary phosphonium cations). The cations104can be linked to the terephthalamide structure via one or more linkage groups (e.g., alkyl groups and/or aryl groups). Further, one or more of the cations104can be bonded to one or more of the hydrophobic functional groups106. Additionally, the repeating ionene unit100can repeat a number of times greater than or equal to 2 and less than or equal to 1000. Therefore, the repeating ionene unit100contacting the pathogen at1002can comprise any and all the features of various embodiments described herein.