Chemical compositions with antimicrobial functionality

Techniques regarding killing of a pathogen with one or more ionene compositions having antimicrobial functionality are provided. For example, one or more embodiments can comprise a method, which can comprise contacting a Mycobacterium tuberculosis microbe with a chemical compound. The chemical compound can comprise an ionene unit. Also, the ionene unit can comprise a cation distributed along a molecular backbone. The ionene unit can have antimicrobial functionality. The method can further comprise electrostatically disrupting a membrane of the Mycobacterium tuberculosis microbe in response to the contacting.

BACKGROUND

The subject disclosure relates to one or more ionene compositions with antimicrobial functionality, and more specifically, to one or more ionene compositions capable of killing and/or preventing growth of a pathogen.

SUMMARY

According to an embodiment, a method is provided. The method can comprise contacting aMycobacterium tuberculosismicrobe with a chemical compound. The chemical compound can comprise an ionene unit. Also, the ionene unit can comprise a cation distributed along a molecular backbone. The ionene unit can have antimicrobial functionality. The method can further comprise electrostatically disrupting a membrane of theMycobacterium tuberculosismicrobe in response to the contacting.

According to another embodiment, a method is provided. The method can comprise contacting aMycobacterium aviumcomplex microbe with a chemical compound. The chemical compound can comprise an ionene unit. Also, the ionene unit can comprise a cation distributed along a molecular backbone. The ionene unit can have antimicrobial functionality. The method can further comprise electrostatically disrupting a membrane of theMycobacterium aviumcomplex microbe in response to the contacting.

According to another embodiment, a method is provided. The method can comprise contacting a pathogen with a chemical compound. The chemical compound can comprise an ionene unit. The ionene unit can comprise a cation distributed along a molecular backbone. Additionally, the molecular backbone can comprise a bis(urea)guanidinium structure, and the ionene unit can have antimicrobial functionality. The method can further comprise electrostatically disrupting a membrane of the pathogen in response to the contacting.

According to another embodiment, a method is provided. The method can comprise contacting a pathogen with a chemical compound. The chemical compound can comprise an ionene unit. Also, the ionene unit can comprise a cation distributed along a molecular backbone. The molecular backbone can comprise a terephthalamide structure, and the ionene unit can have antimicrobial functionality. The method can further comprise electrostatically disrupting a membrane of the pathogen in response to the contacting.

According to another embodiment, a method is provided. The method can comprise targeting a pathogen with a chemical compound through electrostatic interaction between the chemical compound and a membrane of the pathogen. The chemical compound can comprise an ionene unit. The ionene unit can comprise a cation distributed along a molecular backbone. Additionally, the ionene unit can comprise a hydrophobic functional group covalently bonded to the molecular backbone. The method can further comprise destabilizing the membrane of the pathogen through integration of the hydrophobic functional group into the membrane of the pathogen.

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-resistant Enterococci (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.

Current antibiotic therapies are inefficient to treat biofilm protected and intracellular infections such asMycobacterium tuberculosis(TB) and related strains, allowing bacteria to establish chronic medication resistant infections. The Gates Foundation estimates that 8.6 million new TB cases are reported each year resulting in 1.3 million deaths worldwide. The World Health Organization (WHO) estimates approximately 9 to 10 million new TB cases per year. Pulmonary non-tuberculosis mycobacteria (NTM) cases, includingMycobacterium aviumcomplex (MAC), are estimated by some experts to be at least ten times more common than TB in the U.S., with at least 150,000 new cases per year. Given the reduction of effective treatment options for TB and MAC, and diminished antibiotic discovery and development pipeline, a new therapeutic development paradigm is needed for perpetual treatment of increasingly resistant TB and MAC infections.

TB and other mycobacteria strains including MAC can be extremely difficult to eradicate compared to other types of bacteria due to their ability to encapsulate bacterial colonies with extracellular biofilm secretions to block existing antibiotic activity. However, chemical compounds having a cationic charge can provide electrostatic disruption of the bacterial membrane interaction. Furthermore, cationic polymers can be 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 chemical compounds can show relatively low selectivity as defined by the relative toxicity to mammalian cells or hemolysis relative to pathogens.

Various embodiments described herein can regard chemical compounds and/or methods that can target mycolic acid, a cell wall component of theMycobacterium tuberculosis(Mtb) bacilli, using a mechanism of action that can prevent resistance development and can avoid nonspecific toxicity. For example, one or more embodiments described herein can comprise small molecular compounds and macromolecular chemical compounds, which can have bis(urea)guanidinium functionalities. The bis(urea)guanidine structure can allow for a unique combination of hydrogen-bonding capabilities with strong association constants with the mycolic acid. Collectively, ionic interactions associated with the cationic charges on the chemical compounds together with the hydrogen bonding associated with the bis(urea)guanidine structures can provide a cooperative but orthogonal association with Mtb through the mycolic acid that can amplify the targeting, selectivity and potency towards Mtb. Further, said physical interactions can prevent resistance development. Additionally, one or more embodiments described herein (e.g., methods of killing a pathogen comprising one or more chemical compounds having a bis(urea)guanidinium structure) can exhibit negligible toxicity against L929 mouse fibroblast cell line, and cell viability can be more than 85% after 48-h incubation with the compound at 250 micrograms per milliliter (μg/mL), which is well above its minimum inhibitory concentration (MIC) (e.g., 2-4 μg/mL).

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, yeast cells,Mycobacterium tuberculosismicrobes,Mycobacterium aviumcomplex microbes, and/orMycobacterium abscessusmicrobes.

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 example, non-limiting chemical formulas that can characterize one or more ionene 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. The first chemical formula200can characterize one or more ionene units100comprising a molecular backbone102with one or more terephthalamide structures. The second chemical formula202can characterize one or more ionene units with a molecular backbone102comprising one or more bis(urea)guanidinium structures. The chemical formulas depicted inFIG. 2(e.g., the first chemical formula200and/or the second chemical formula202) can comprise monomers and/or polymers (e.g., homopolymers, alternating copolymers, and/or random copolymers). In addition, the one or more ionene units100that can be characterized by the first chemical formula200can be bonded to one or more other ionene units100that can be characterized by the second chemical formula200to form one or more chemical compounds (e.g., ionenes, polyionones, monomers, and/or polymers).

As shown inFIG. 2, an ionene unit100characterized by the first chemical formula200and/or the second chemical formula202can comprise a degradable molecular backbone102. In one or more embodiments, an ionene unit100characterized by the first 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 the first chemical formula200can comprise one or more terephthalamide structures derived from one or more molecules other than PET. In various embodiments, an ionene unit100characterized by the second chemical formula202can be derived from 1,3-bis(butoxycarbonyl)guanidine, wherein the one or more guanidinium groups can be derived from the 1,3-bis(butoxycarbonyl)guanidine. However, one or more embodiments of the second chemical formula202can comprise one or more bis(urea)guanidinium structures derived from one or more molecules other than 1,3-bis(butoxycarbonyl)guanidine.

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 the first chemical formula200and/or the second chemical formula202) 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 one or more terephthalamide structures (e.g., as characterized by the first chemical formula200) and/or one or more bis(urea)guanidinium structures (e.g., as characterized by the second chemical formula202), thereby comprising the molecular backbone102. The “L” 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, alkenyl structures, aldehyde structures, ester structures, carboxyl structures, carbonyl structures, a combination thereof, and/or the like. For instance, “L” 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, one or more ionene units100characterized by the first chemical formula200and/or the second chemical formula202can 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 the first chemical formula200and/or the second chemical formula202, 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 one or more dialkyl halides. Example dialkyl halides 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; 1,4-bis(iodomethyl)benzene; 1,6-dibromohexane; 1,8-dibromooctane; 1,12-dibromododecane; 1,6-dichlorohexane; 1,8-dichlorooctane; a combination thereof; and/or the like. 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 “L” inFIG. 2), and/or one or more bis(urea)guanidinium structures and/or terephthalamide structures.

In one or more embodiments, one or more ionene units100characterized by the first chemical formula200can also comprise one or more hydrophilic functional groups. The one or more hydrophilic functional groups can: increase degradability of the one or more ionene units100, impart carbohydrate mimetic functionality to the one or more ionene units100, and/or increase mobility (e.g., intracellular mobility) of the one or more ionene units100. For example, the one or more hydrophilic functional groups can be derived from a polyol and have one or more hydroxyl functional groups. In another example, the one or more hydrophilic functional groups can be derived from a block polymer, can be water-soluble, can be bioinert, and/or can comprise one or more ether groups.

Additionally, one or more ionene units100characterized by the second chemical formula202can have supramolecular functionality. For example, the one or more bis(urea)guanidinium structures can facilitate supramolecular assembly of the one or more ionene units100to form a supramolecule.

Moreover, an ionene and/or polyionene characterized by the first chemical formula200and/or the second chemical formula202can comprise a single ionene unit100or a repeating ionene unit100. For example, the “n” shown inFIG. 2can represent a first integer greater than or equal to one and less than or equal to one thousand.

FIG. 3illustrates an example, non-limiting first ionene composition302comprising an 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. For example, the first ionene composition302can be in accordance with the various features described herein regardingFIG. 1A-1B. The one or more cations104comprising the first ionene composition302can be quaternary ammonium cations. Additionally, the one or more hydrophobic functional groups106comprising the first ionene composition302can be an aromatic ring along the first ionene composition's302molecular backbone102. Moreover, the “n” shown inFIG. 3can represent an integer greater than or equal to one and less than or equal to one thousand.

FIG. 4illustrates example, non-limiting ionene compositions that can be characterized by the first chemical formula200in 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 “n” shown inFIG. 4can represent an integer greater than or equal to one and less than or equal to one thousand. The “m” shown inFIG. 4can represent another integer greater than or equal to one and less than or equal to one thousand. The “x” shown inFIG. 4can represent another integer greater than or equal to one and less than or equal to one thousand. The “y” shown inFIG. 4can represent another integer greater than or equal to one and less than or equal to one thousand. The ionene compositions depicted inFIG. 4can comprise monomers and/or polymers (e.g., homopolymers, alternating copolymers, and/or random copolymers).

The second ionene composition402(e.g., comprising an ionene unit100that can be characterized by the first chemical formula200) can comprise a degradable molecular backbone102having one or more terephthalamide structures. The one or more cations104of the second composition402can be quaternary ammonium cations. Further, the one or more hydrophobic functional groups106can comprise one or more aromatic rings bonded to one or more of the cations104(e.g., one or more quaternary ammonium cations).

The third ionene composition404(e.g., comprising an ionene unit100that can be characterized by the first chemical formula200) can comprise a degradable molecular backbone102having one or more terephthalamide structures. The one or more cations104of the third composition404can be quaternary ammonium cations. Further, the one or more hydrophobic functional groups106can comprise one or more aromatic rings bonded to one or more of the cations104(e.g., one or more quaternary ammonium cations). Moreover, the third ionene composition404can comprise one or more hydrophilic functional groups. The one or more hydrophilic functional groups can be: derived from a block polymer, water-soluble, and/or bioinert. The one or more hydrophilic functional groups can be bonded to one or more cations104(e.g., quaternary ammonium cations). For example, the one or more hydrophilic functional groups can comprise a poly(propylene glycol)-block-poly(ethylene glycol)-block-poly(propylene glycol) bis(2-aminopropyl ether) (ED) structure having a molecular weight greater than or equal to 1900 grams per mole (g/mol) and less than or equal to 2200 g/mol (ED2000).

The fourth ionene composition406(e.g., comprising an ionene unit100that can be characterized by the first chemical formula200) can comprise a degradable molecular backbone102having one or more terephthalamide structures. The one or more cations104of the fourth composition406can be quaternary ammonium cations. Further, the one or more hydrophobic functional groups106can comprise one or more aromatic rings bonded to one or more of the cations104(e.g., one or more quaternary ammonium cations). Moreover, the fourth ionene composition406can comprise one or more hydrophilic functional groups. The one or more hydrophilic functional groups can be derived from a polyol, can comprise one or more hydroxyl groups, and/or can exhibit carbohydrate mimetic functionality. Also, the one or more hydrophilic functional groups can be bonded to the one or more hydrophobic functional groups106. In addition, the one or more hydrophilic functional groups can comprise additional cations104(e.g., quaternary ammonium cations).

The fifth ionene composition408(e.g., comprising an ionene unit100that can be characterized by the first chemical formula200) can comprise a degradable molecular backbone102having one or more terephthalamide structures. The one or more cations104of the fifth composition408can be imidazolium cations. Further, the one or more hydrophobic functional groups106can comprise one or more alkyl chains bonded to one or more of the cations104(e.g., one or more imidazolium cations).

The sixth ionene composition410(e.g., comprising an ionene unit100that can be characterized by the first chemical formula200) can comprise a degradable molecular backbone102having one or more terephthalamide structures. The one or more cations104of the sixth composition410can be quaternary ammonium cations. Further, the one or more hydrophobic functional groups106can comprise one or more aromatic rings bonded to one or more of the cations104(e.g., one or more quaternary ammonium cations). Moreover, the sixth ionene composition410can comprise one or more hydrophilic functional groups. The one or more hydrophilic functional groups can comprise one or more ether groups. Also, the one or more hydrophilic functional groups can be bonded to the one or more hydrophobic functional groups106. In addition, the one or more hydrophilic functional groups can comprise additional cations104(e.g., quaternary ammonium cations).

The seventh ionene composition412(e.g., comprising an ionene unit100that can be characterized by the first chemical formula200) can comprise a degradable molecular backbone102having a plurality of terephthalamide structures. The one or more cations104of the seventh composition412can be quaternary ammonium cations. Further, the one or more hydrophobic functional groups106can comprise one or more aromatic rings, and can be bonded to one or more of the cations104(e.g., one or more quaternary ammonium cations). Moreover, the seventh ionene composition412can comprise one or more hydrophilic functional groups. The one or more hydrophilic functional groups can be: derived from a block polymer, water-soluble, and/or bioinert. The one or more hydrophilic functional groups can be bonded to one or more cations104(e.g., quaternary ammonium cations). Also, the one or more hydrophilic functional groups can comprise one or more ether groups.

The eighth ionene composition414(e.g., comprising an ionene unit100in accordance withFIG. 1A) can comprise a molecular backbone102comprising one or more ether groups. The one or more cations104of the eighth ionene composition414can be quaternary ammonium cations. Further, the one or more hydrophobic functional groups106can comprise one or more aromatic rings, and can be bonded to one or more cations104(e.g., one or more quaternary ammonium cations).

FIG. 5illustrates example, non-limiting ionene compositions that can be characterized by the second chemical formula202in 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 “n” shown inFIG. 5can represent an integer greater than or equal to one and less than or equal to one thousand. The ionene compositions depicted inFIG. 5can comprise monomers and/or polymers (e.g., homopolymers, alternating copolymers, and/or random copolymers).

The ninth ionene composition502(e.g., comprising an ionene unit100that can be characterized by the second chemical formula202) can comprise a degradable molecular backbone102having one or more bis(urea)guanidinium structures. The one or more cations104of the ninth composition502can be quaternary ammonium cations. Further, the one or more hydrophobic functional groups106can comprise one or more aromatic rings bonded to one or more of the cations104(e.g., one or more quaternary ammonium cations).

The tenth ionene composition504(e.g., comprising an ionene unit100that can be characterized by the second chemical formula202) can comprise a degradable molecular backbone102having one or more bis(urea)guanidinium structures. The one or more cations104of the second composition402can be imidazolium cations. Further, the one or more hydrophobic functional groups106can comprise one or more aromatic rings bonded to one or more of the cations104(e.g., one or more imidazolium cations).

The eleventh ionene composition506(e.g., comprising an ionene unit100that can be characterized by the second chemical formula202) can comprise a degradable molecular backbone102having a plurality of bis(urea)guanidinium structures. The one or more cations104of the second composition402can be imidazolium cations. Further, the one or more hydrophobic functional groups106can comprise one or more aromatic rings bonded to one or more of the cations104(e.g., one or more imidazolium cations). For example, one or more of the hydrophobic functional groups106can be bonded to two or more cations104(e.g., two or more imidazolium cations). In one or more embodiments, the eleventh ionene composition506can be further modified (e.g., functionalized). For example, one or more additional functional groups can replace and/or modify one or more of the tert-butyl groups located at the peripheries of the eleventh ionene composition506. For instance, Scheme 1, presented below, can depict an exemplary modification to the eleventh ionene composition.

FIG. 6illustrates a flow diagram of an example, non-limiting method600that can facilitate killing aMycobacterium tuberculosismicrobe, preventing the growth of aMycobacterium tuberculosismicrobe, and/or preventing contamination by aMycobacterium tuberculosismicrobe. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity.

At602, the method600can comprise contacting aMycobacterium tuberculosismicrobe with one or more chemical compounds. The one or more chemical compounds can comprise one or more ionene units100(e.g., characterized by the first chemical formula200and/or the second chemical formula202). The one or more ionene units100can comprise one or more cations104(e.g., represented by “X” inFIG. 2) distributed along a molecular backbone102. The one or more cations104can comprise nitrogen cations and/or phosphorus cations. Example nitrogen cations can include, but are not limited to: protonated secondary amine cations, protonated tertiary amine cations, quaternary ammonium cations, and/or imidazolium cations. Example phosphorus cations can include, but are not limited to: protonated secondary phosphine cations, protonated tertiary phosphine cations, and/or quaternary phosphonium cations. The molecular backbone102can be degradable. Further, the molecular backbone102can comprise one or more terephthalamide structures and/or one or more bis(urea)guanidinium structures. The one or more ionene units100can have: antimicrobial functionality, supramolecular assembly functionality, and/or carbohydrate mimetic functionality.

At604, the method600can comprise electrostatically disrupting a membrane of theMycobacterium tuberculosismicrobe in response to the contacting at602. The membrane of theMycobacterium tuberculosismicrobe can comprise a phospholipid bilayer as described regardingFIG. 1B. Further, the electrostatic disruption at604can be facilitated by one or more interactions between the one or more cations104of the ionene unit100and/or one or more negatively charged membrane molecules112that can comprise the membrane of theMycobacterium tuberculosismicrobe.

Furthermore, the ionene unit100can comprise one or more hydrophobic functional groups106. The one or more hydrophobic functional groups106can be derived from dialkyl halides and can comprise alkyl and/or aryl structures. Additionally, the one or more hydrophobic functional groups106can be covalently bonded to the molecular backbone102(e.g., via bonding with one or more cations104). Additionally, the method600can further comprise destabilizing the membrane of theMycobacterium tuberculosismicrobe through integration of the hydrophobic functional group106into the membrane (e.g., as depict at120and/or122of the lysis process108).

In one or more embodiments, the ionene unit100can further comprise one or more hydrophilic functional groups. The one or more hydrophilic functional groups can: increase degradability of the one or more ionene units100, impart carbohydrate mimetic functionality to the one or more ionene units100, and/or increase mobility (e.g., intracellular mobility) of the one or more ionene units100. For example, the one or more hydrophilic functional groups can be derived from a polyol and have one or more hydroxyl functional groups. In another example, the one or more hydrophilic functional groups can be derived from a block polymer, can be water-soluble, can be bioinert, and/or can comprise one or more ether groups.

In one or more embodiments, the one or more ionene units100can supramolecularly assemble with theMycobacterium tuberculosismicrobe. For example, one or more bis(urea)guanidinium structures comprising the molecular backbone102of the one or more ionene units100can facilitate supramolecular assembly of the one or more chemical compounds with theMycobacterium tuberculosismicrobe to form a supramolecular assembly.

Thus, the one or more chemical compounds can be monomers (e.g., ionenes) and/or polymers (e.g., polyionenes such as homopolymers, alternating copolymers, and/or random copolymers). The one or more ionene units100comprising the one or more compounds utilized in method600can be characterized by the first chemical formula200and/or the second chemical formula202. For example, the one or more chemical compounds can comprise any of the ionene compositions described herein (e.g., with regard toFIGS. 3-5). Additionally, the method600can facilitate conducting a lysis process108regarding theMycobacterium tuberculosismicrobe.

FIG. 7illustrates a flow diagram of an example, non-limiting method700that can facilitate killing aMycobacterium aviumcomplex microbe, preventing the growth of aMycobacterium aviumcomplex microbe, and/or preventing contamination by aMycobacterium aviumcomplex microbe. Repetitive description of like elements employed in other embodiments described herein is omitted for sake of brevity.

At702, the method700can comprise contacting aMycobacterium aviumcomplex microbe with one or more chemical compounds. The one or more chemical compounds can comprise one or more ionene units100(e.g., characterized by the first chemical formula200and/or the second chemical formula202). The one or more ionene units100can comprise one or more cations104(e.g., represented by “X” inFIG. 2) distributed along a molecular backbone102. The one or more cations104can comprise nitrogen cations and/or phosphorus cations. Example nitrogen cations can include, but are not limited to: protonated secondary amine cations, protonated tertiary amine cations, quaternary ammonium cations, and/or imidazolium cations. Example phosphorus cations can include, but are not limited to: protonated secondary phosphine cations, protonated tertiary phosphine cations, and/or quaternary phosphonium cations. The molecular backbone102can be degradable. Further, the molecular backbone102can comprise one or more terephthalamide structures and/or one or more bis(urea)guanidinium structures. The one or more ionene units100can have: antimicrobial functionality, supramolecular assembly functionality, and/or carbohydrate mimetic functionality.

At704, the method700can comprise electrostatically disrupting a membrane of theMycobacterium aviumcomplex microbe in response to the contacting at702. The membrane of theMycobacterium aviumcomplex microbe can comprise a phospholipid bilayer110as described regardingFIG. 1B. Further, the electrostatic disruption at704can be facilitated by one or more interactions between the one or more cations104of the ionene unit100and/or one or more negatively charged membrane molecules112that can comprise the membrane of theMycobacterium aviumcomplex microbe.

Furthermore, the ionene unit100can comprise one or more hydrophobic functional groups106. The one or more hydrophobic functional groups106can be derived from dialkyl halides and can comprise alkyl and/or aryl structures. Additionally, the one or more hydrophobic functional groups106can be covalently bonded to the molecular backbone102(e.g., via bonding with one or more cations104). Additionally, the method700can further comprise destabilizing the membrane of theMycobacterium aviumcomplex microbe through integration of the hydrophobic functional group106into the membrane (e.g., as depict at120and/or122of the lysis process108).

In one or more embodiments, the ionene unit100can further comprise one or more hydrophilic functional groups. The one or more hydrophilic functional groups can: increase degradability of the one or more ionene units100, impart carbohydrate mimetic functionality to the one or more ionene units100, and/or increase mobility (e.g., intracellular mobility) of the one or more ionene units100. For example, the one or more hydrophilic functional groups can be derived from a polyol and have one or more hydroxyl functional groups. In another example, the one or more hydrophilic functional groups can be derived from a block polymer, can be water-soluble, can be bioinert, and/or can comprise one or more ether groups.

Thus, the one or more chemical compounds can be monomers (e.g., ionenes) and/or polymers (e.g., polyionenes such as homopolymers, alternating copolymers, and/or random copolymers). The one or more ionene units100comprising the one or more compounds utilized in method700can be characterized by the first chemical formula200and/or the second chemical formula202. For example, the one or more chemical compounds can comprise any of the ionene compositions described herein (e.g., with regard toFIGS. 3-5). Additionally, the method700can facilitate conducting a lysis process108regarding theMycobacterium aviumcomplex microbe.

FIG. 8illustrates a flow diagram of an example, non-limiting method800that can facilitate 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 can include, but are not limited to: Gram-negative microbe, a Gram-positive microbe, a fungus, a yeast, aMycobacterium tuberculosismicrobe, aMycobacterium aviumcomplex microbe, and/or aMycobacterium abscessusmicrobe.

At802, the method800can comprise contacting the pathogen with one or more chemical compounds. The one or more chemical compounds can comprise one or more ionene units100(e.g., characterized by the second chemical formula202). The one or more ionene units100can comprise one or more cations104(e.g., represented by “X” inFIG. 2) distributed along a molecular backbone102. The one or more cations104can comprise nitrogen cations and/or phosphorus cations. Example nitrogen cations can include, but are not limited to: protonated secondary amine cations, protonated tertiary amine cations, quaternary ammonium cations, and/or imidazolium cations. Example phosphorus cations can include, but are not limited to: protonated secondary phosphine cations, protonated tertiary phosphine cations, and/or quaternary phosphonium cations. The molecular backbone102can be degradable. Further, the molecular backbone102can comprise one or more bis(urea)guanidinium structures. The one or more ionene units100can have: antimicrobial functionality and/or supramolecular assembly functionality.

At804, the method800can comprise electrostatically disrupting a membrane of the pathogen in response to the contacting at802. The membrane of the pathogen can comprise a phospholipid bilayer110as described regardingFIG. 1B. Further, the electrostatic disruption at804can be facilitated by one or more interactions between the one or more cations104of the ionene unit100and/or one or more negatively charged membrane molecules112that can comprise the membrane of the pathogen.

Additionally, one or more ionene units100characterized by the second chemical formula202can have supramolecular functionality. For example, the one or more bis(urea)guanidinium structures can facilitate supramolecular assembly of the one or more ionene units100with the pathogen to form a supramolecule.

Thus, the one or more chemical compounds can be monomers (e.g., ionenes) and/or polymers (e.g., polyionenes such as homopolymers, alternating copolymers, and/or random copolymers). The one or more ionene units100comprising the one or more compounds utilized in method800can be characterized by the second chemical formula202. For example, the one or more chemical compounds can comprise one or more of the ionene compositions described regardingFIG. 5. Additionally, the method800can facilitate conducting a lysis process108regarding the pathogen.

FIG. 9illustrates a flow diagram of an example, non-limiting method900that can facilitate 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 can include, but are not limited to: Gram-negative microbe, a Gram-positive microbe, a fungus, a yeast, aMycobacterium tuberculosismicrobe, aMycobacterium aviumcomplex microbe, and/or aMycobacterium abscessusmicrobe.

At902, the method900can comprise contacting the pathogen with one or more chemical compounds. The one or more chemical compounds can comprise one or more ionene units100(e.g., characterized by the first chemical formula200). The one or more ionene units100can comprise one or more cations104(e.g., represented by “X” inFIG. 2) distributed along a molecular backbone102. The one or more cations104can comprise nitrogen cations and/or phosphorus cations. Example nitrogen cations can include, but are not limited to: protonated secondary amine cations, protonated tertiary amine cations, quaternary ammonium cations, and/or imidazolium cations. Example phosphorus cations can include, but are not limited to: protonated secondary phosphine cations, protonated tertiary phosphine cations, and/or quaternary phosphonium cations. The molecular backbone102can be degradable. Further, the molecular backbone102can comprise one or more terephthalamide structures. The one or more ionene units100can have: antimicrobial functionality and/or carbohydrate mimetic functionality.

At904, the method900can comprise electrostatically disrupting a membrane of the pathogen in response to the contacting at902. The membrane of the pathogen can comprise a phospholipid bilayer as described regardingFIG. 1B. Further, the electrostatic disruption at904can be facilitated by one or more interactions between the one or more cations104of the ionene unit100and/or one or more negatively charged membrane molecules112that can comprise the membrane of the pathogen.

Furthermore, the ionene unit100can comprise one or more hydrophobic functional groups106. The one or more hydrophobic functional groups106can be derived from dialkyl halides and can comprise alkyl and/or aryl structures. Additionally, the one or more hydrophobic functional groups106can be covalently bonded to the molecular backbone102(e.g., via bonding with one or more cations104). Additionally, the method900can further comprise destabilizing the membrane of the pathogen through integration of the hydrophobic functional group106into the membrane (e.g., as depict at120and/or122of the lysis process108).

In one or more embodiments, the ionene unit100can further comprise one or more hydrophilic functional groups. The one or more hydrophilic functional groups can: increase degradability of the one or more ionene units100, impart carbohydrate mimetic functionality to the one or more ionene units100, and/or increase mobility (e.g., intracellular mobility) of the one or more ionene units100. For example, the one or more hydrophilic functional groups can be derived from a polyol and have one or more hydroxyl functional groups. In another example, the one or more hydrophilic functional groups can be derived from a block polymer, can be water-soluble, can be bioinert, and/or can comprise one or more ether groups.

Thus, the one or more chemical compounds can be monomers (e.g., ionenes) and/or polymers (e.g., polyionenes such as homopolymers, alternating copolymers, and/or random copolymers). The one or more ionene units100comprising the one or more compounds utilized in method900can be characterized by the first chemical formula200. For example, the one or more chemical compounds can comprise any of the ionene compositions described regardingFIGS. 3-4. Additionally, the method900can facilitate conducting a lysis process108regarding the pathogen.

FIG. 10illustrates a flow diagram of an example, non-limiting method1000that can facilitate 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 can include, but are not limited to: Gram-negative microbe, a Gram-positive microbe, a fungus, a yeast, aMycobacterium tuberculosismicrobe, aMycobacterium aviumcomplex microbe, and/or aMycobacterium abscessusmicrobe.

At1002, the method1000can comprise targeting a pathogen with one or more chemical compounds through electrostatic interaction between the one or more chemical compounds and a membrane of the pathogen. For example, the targeting at1002can be facilitated by one or more interactions between the one or more cations104of the chemical compound and/or one or more negatively charged membrane molecules112that can comprise the membrane of the pathogen.

The one or more chemical compounds can comprise one or more ionene units100(e.g., characterized by the first chemical formula200and/or the second chemical formula202). The one or more ionene units100can comprise the one or more cations104(e.g., represented by “X” inFIG. 2) distributed along a molecular backbone102. The one or more cations104can comprise nitrogen cations and/or phosphorus cations. Example nitrogen cations can include, but are not limited to: protonated secondary amine cations, protonated tertiary amine cations, quaternary ammonium cations, and/or imidazolium cations. Example phosphorus cations can include, but are not limited to: protonated secondary phosphine cations, protonated tertiary phosphine cations, and/or quaternary phosphonium cations. The molecular backbone102can be degradable. Further, the molecular backbone102can comprise one or more terephthalamide structures and/or one or more bis(urea)guanidinium structures. The one or more ionene units100can have: antimicrobial functionality, supramolecular assembly functionality, and/or carbohydrate mimetic functionality.

Furthermore, the ionene unit100can comprise one or more hydrophobic functional groups106. The one or more hydrophobic functional groups106can be derived from dialkyl halides and can comprise alkyl and/or aryl structures. Additionally, the one or more hydrophobic functional groups106can be covalently bonded to the molecular backbone102(e.g., via bonding with one or more cations104).

At1004, the method1000can further comprise destabilizing the membrane of the pathogen through integration of the one or more hydrophobic functional groups106into the membrane of the pathogen. For example, the one or more hydrophobic functional groups106can integrate into a hydrophobic region of the membrane as depicted at120and/or122of the lysis process108. Integration of the one or more hydrophobic functional groups106can compromise the integrity of the pathogen's membrane, thereby facilitating the lysis process108.

In one or more embodiments, the ionene unit100can further comprise one or more hydrophilic functional groups. The one or more hydrophilic functional groups can: increase degradability of the one or more ionene units100, impart carbohydrate mimetic functionality to the one or more ionene units100, and/or increase mobility (e.g., intracellular mobility) of the one or more ionene units100. For example, the one or more hydrophilic functional groups can be derived from a polyol and have one or more hydroxyl functional groups. In another example, the one or more hydrophilic functional groups can be derived from a block polymer, can be water-soluble, can be bioinert, and/or can comprise one or more ether groups.

In one or more embodiments, the one or more ionene units100can supramolecularly assemble with the pathogen. For example, one or more bis(urea)guanidinium structures comprising the molecular backbone102of the one or more ionene units100can facilitate supramolecular assembly of the one or more chemical compounds with the pathogen to form a supramolecular assembly.

Thus, the one or more chemical compounds can be monomers (e.g., ionenes) and/or polymers (e.g., polyionenes such as homopolymers, alternating copolymers, and/or random copolymers). The one or more ionene units100comprising the one or more compounds utilized in method1000can be characterized by the first chemical formula200and/or the second chemical formula202. For example, the one or more chemical compounds can comprise any of the ionene compositions described herein (e.g., with regard toFIGS. 3-5). Additionally, the method1000can facilitate conducting a lysis process108regarding theMycobacterium tuberculosismicrobe.

FIG. 11illustrates three micrographs of an example, non-limiting lysis process108of aMycobacterium tuberculosis3360(Mtb3360) microbe, which is a clinical strain ofMycobacterium tuberculosis, 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.FIG. 11can depict transmission electron microscopy (TEM) micrographs of a Mtb3360microbe undergoing a lysis process108facilitated by the fifth ionene composition408at a concentration of 32 micrograms per milliliter (μg/mL). The first micrograph1102can depict the Mtb3360microbe before being contacted with the fifth ionene composition408. The second micrograph1104and/or the third micrograph1106can depict the Mtb3360microbe after being contacted with the fifth ionene composition408for 24 hours.

FIG. 12Aillustrates a diagram of an example, non-limiting chart1200that can depict the antimicrobial efficacy of one or more ionene 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 ionene compositions (e.g., that can be characterized by first chemical formula200and/or second chemical formula202and exemplified inFIGS. 3-5) and methods (e.g., methods600,700,800,900, and/or1000) described herein a plurality of polyionene compositions were evaluated against a broad spectrum of pathogens.

The first column1202of chart1200can depict the ionene composition subject to evaluation. The second column1204of chart1200can depict the minimum inhibitory concentration (MIC) in μg/mL of the subject ionene composition regardingStaphylococcus aureus(“SA”). The third column1206of chart1200can depict the MIC in μg/mL of the subject ionene composition regardingEscherichia coli(“EC”). The fourth column1208of chart1200can depict the MIC in μg/mL of the subject ionene composition regardingPseudomonas aeruginosa(“PA”). The fifth column1210of chart1200can depict the MIC in μg/mL of the subject ionene composition regardingCandida albicans(“CA”). The sixth column1212of chart1200can depict the MIC in μg/mL of the subject ionene composition regarding Mtb3360. The seventh column1214of chart1200can depict the MIC in μg/mL of the subject ionene composition regarding Mtb3361, which is another clinical strain ofMycobacterium tuberculosis.

FIG. 12Billustrates a diagram of an example, non-limiting chart1216that can depict the antimicrobial efficacy of one or more ionene 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 ionene compositions (e.g., that can be characterized by first chemical formula200and/or second chemical formula202and exemplified inFIGS. 3-5) and methods (e.g., methods600,700,800,900, and/or1000) described herein a plurality of polyionene compositions were evaluated againstMycobacterium aviumcomplex and/orMycobacterium abscessus4064, which is a clinical strain ofMycobacterium abscessus.

The left column1218of chart1216can depict the ionene composition subject to evaluation. The middle column1220of chart1216can depict the MIC in μg/mL of the subject ionene composition regardingMycobacterium aviumcomplex. The right column1222of chart1200can depict the MIC in μg/mL of the subject ionene composition regardingMycobacterium abscessus4064.