Sulfobetaine Group Research Articles

Sulfobetaine-Siloxanes: A Class of Self-Destructive Surfactants.

The hydrolytic susceptibility of sulfobetaine-siloxane surfactants is investigated by comparison of a homologous series in this subclass of surfactants (R-(CH2)3N+(Me)2(CH2)3SO3-; R = (Me3SiO)3Si-, (Me3SiO)2Si(Me)-, (Me2SiO)3-Si(Me)-) with an analogue series of oxyethylene-siloxane surfactants (R-(CH2)3(OCH2CH2)10.2OH; R = (Me3SiO)3Si-, (Me3SiO)2Si(Me)-, (Me2SiO)3-Si(Me)-). Nuclear magnetic resonance (NMR) monitoring of these surfactants in an aqueous solution shows that the presence of the sulfobetaine head structure greatly enhances the hydrolysis rate of the siloxane tail as compared with oxyethylene-siloxane analogue control experiments. This sulfobetaine effect is confirmed by adding a model compound, (Me)3N+(CH2)3SO3-, to the oxyethylene-siloxane surfactants and observing the large hydrolysis enhancement. Measurements of pH indicate the sulfobetaine presence greatly enhances acidity, but rigorous analysis could discover no source of acid other than the presence of the sulfobetaine structure. Titration measurements confirmed the presence of a tightly bound hydration layer of 4-7 water molecules per sulfobetaine group. It is speculated that the source of acidity may originate from an aqueous exclusion zone nucleated by the hydrated sulfobetaine at the interface of a sulfobetaine-siloxane surfactant bilayer aggregate. Hydrolysis prevention is investigated by addition of a pH 7 phosphate buffer, of an alkyl polyglycoside cosurfactant, and of a combination of both, with a finding of very significant but not complete suppression of the hydrolysis.

Low-Fouling and Antibacterial Polymer Brushes via Surface-Initiated Polymerization of a Mixed Zwitterionic and Cationic Monomer.

The use of surface-grafted polymer brushes with combined low-fouling and antibacterial functionality is an attractive strategy to fight biofilm formation. This report describes a new styrene derivative combining a quaternary ammonium group with a sulfobetaine group in one monomer. Surface-initiated polymerization of this monomer on titanium and a polyethylene (PE) base material gave bifunctional polymer brush layers. Grafting was achieved via surface-initiated atom transfer radical polymerization from titanium or heat-induced free-radical polymerization from plasma-activated PE. Both techniques gave charged polymer layers with a thickness of over 750 nm, as confirmed by ToF-SIMS-SPM measurements. The chemical composition of the brush polymers was confirmed by XPS and FT-IR analysis. The surface charge, characterized by the ζ potential, was positive at different pH values, and the number of solvent-accessible excess ammonium groups was found to be ∼1016 N+/cm2. This led to strong antibacterial activity against Gram-positive and Gram-negative bacteria that was superior to a structurally related contact-active polymeric quaternary ammonium brush. In addition to this antibacterial activity, good low-fouling properties of the dual-function polymer brushes against Gram-positive and Gram-negative bacteria were found. This dual functionality is most likely due to the combination of antibacterial quaternary ammonium groups with antifouling sulfobetaines. The combination of both groups in one monomer allows the preparation of bifunctional brush polymers with operationally simple polymerization techniques.

Electroneutral Polymer Nanodiscs Enable Interference-Free Probing of Membrane Proteins in a Lipid-Bilayer Environment.

Membrane proteins can be examined in near-native lipid-bilayer environments with the advent of polymer-encapsulated nanodiscs. These nanodiscs self-assemble directly from cellular membranes, allowing in vitro probing of membrane proteins with techniques that have previously been restricted to soluble or detergent-solubilized proteins. Often, however, the high charge densities of existing polymers obstruct bioanalytical and preparative techniques. Thus, the authorsaim to fabricate electroneutral-yet water-soluble-polymer nanodiscs. By attaching a sulfobetaine group to the commercial polymers DIBMA and SMA(2:1), these polyanionic polymers are converted to the electroneutral maleimide derivatives, Sulfo-DIBMA and Sulfo-SMA(2:1). Sulfo-DIBMA and Sulfo-SMA(2:1) readily extract proteins and phospholipids from artificial and cellular membranes to form nanodiscs. Crucially, the electroneutral nanodiscs avert unspecific interactions, thereby enabling new insights into protein-lipid interactions through lab-on-a-chip detection and in vitro translation of membrane proteins. Finally, the authors create a library comprising thousands of human membrane proteins and use proteome profiling by mass spectrometry to show that protein complexes are preserved in electroneutral nanodiscs.

Triple capacitance via the dehydration of saturated water from carboxylated chitosan bearing zwitterion electrolytes

BackgroundIn the solid-state polymer electrolyte, the saturated water plays an role in increasing ionic conductivity but decreasing the electrochemical window. The water retention effect on zwitterionic polymer electrolyte is investigated in this study. MethodsCarboxylated chitosan (CCS) was subjected to oxa-Michael addition with sulfobetaine methacrylate (SBMA) to produce CCS-SBMA. Its structure was investigated by IR and 1H NMR and used the raman spectrum to observe three different types of water. CCS-SBMA electrolyte and carbon electrode were assembled into supercapacitor for electrochemical testing. Significant findingsCCS-SBMA was grafted 45.7% of sulfobetaine group via Nuclear Magnetic Resonance (NMR) spectra. During dehydration of saturated water from CCS-SBMA polymer electrolyte to 90% retention, the free water proportion decreased, and the bound water proportion increased via Raman spectra analysis. Accordingly, the electrochemical window increased from 1.6V to 2.05V with 10% dehydration of saturated water. Surprisingly, the supercapacitor performance with 90% water retention showed triple specific capacitance of 414.3F/g in comparison with 138.6F/g evaluated from galvanostatic charge-discharge analysis. In this study, CCS-SBMA bearing zwitterion was designed as polymer electrolyte to remain bound water proportion and enhance ion-dissociation during dehydration of saturated water for superior capacitance performance of solid-state supercapacitor.

The strategy of modulation blood responses by surface modification with different functional groups on polyester film.

A main problem in the design of blood-contacting biomaterials has been the deficiency of a systematic understanding of blood-biomaterial interactions and the strategy to modulate blood responses. In this work, different functional groups including carboxyl (COOH), hydroxyl (OH) and zwitterionic sulfobetaine group (⊕N((CH3 )2 )(CH2 )3 SO3-○- , SMDB) were grafted on the poly (butylene terephthalate) (PBT) film to study how the functional groups modulate blood responses and in terms of interaction with the coagulation system, the complement system, and platelets. The results showed protein absorption and platelet adhesion was stronger on the PBT bearing COOH group than PBT films bearing OH and zwitterionic sulfobetaine groups (total protein (μg/cm2 ): 32.92 ± 5.89 vs. 22.02 ± 1.44 vs. 19.09 ± 1.59; platelet adhesion (/mm2 ): 1,626.7 ± 120.1 vs. 1,395.6 ± 363.3 vs. 1,102.2 ± 373.7), which had a rougher and negatively charged surface, and the coagulation system was inhibited by binding fibrinogen (Fg) and coagulation factors. Meanwhile, PBT-PSMDB showed anticoagulant property and induced platelet activation. As a result, complement formation on these two films were less than PBT bearing OH groups by inhibiting the coagulation system (C3a (ng/ml): 3,745.4 ± 143.9 vs. 3,290.9 ± 249.7 vs. 4,887.9 ± 88.9; C5a (ng/ml): 22.1 ± 2.6 vs. 22.3 ± 1.8 vs. 27.9 ± 2.0). On the other hand, PBT bearing OH groups did not facilitate remarkable platelet adhesion and activation, and had no influence on platelet aggregation, hypotonic shock response, and coagulation system. The above results showed that the blood responses were highly interlinked, and could be modulated by grafting with different functional groups on the biomaterial surfaces. These findings may help identify a strategy to design materials with better hemocompatibility for blood contact, filtration, and purification applications.

Sulfobetaine Methacrylate Polymers of Unconventional Polyzwitterion Architecture and Their Antifouling Properties

Combining high hydrophilicity with charge neutrality, polyzwitterions are intensely explored for their high biocompatibility and low-fouling properties. Recent reports indicated that in addition to charge neutrality, the zwitterion's segmental dipole orientation is an important factor for interacting with the environment. Accordingly, a series of polysulfobetaines with a novel architecture was designed, in which the cationic and anionic groups of the zwitterionic moiety are placed at equal distances from the backbone. They were investigated by in vitro biofouling assays, covering proteins of different charges and model marine organisms. All polyzwitterion coatings reduced the fouling effectively compared to model polymer surfaces of poly(butyl methacrylate), with a nearly equally good performance as the reference polybetaine poly(3-(N-(2-(methacryloyloxy)ethyl)-N,N-dimethylammonio)propanesulfonate). The specific fouling resistance depended on the detailed chemical structure of the polyzwitterions. Still, while clearly affecting the performance, the precise dipole orientation of the sulfobetaine group in the polyzwitterions seems overall to be only of secondary importance for their antifouling behavior.

Evaluation of protein corona formation and anticancer efficiency of curcumin-loaded zwitterionic silica nanoparticles

Objective(s): Study and development of antifouling nanosystem for conjugation of drugs were attracting great attention in recent years. The present study aimed to develop novel curcumin-loaded silica nanoparticles containing zwitterionic coating as an antifouling system to provide protein corona free nanoformulations for curcumin. Materials and Methods: Silica nanoparticles were prepared using the Stober method, and mono- and bi-functionalized nanoparticles were obtained by modifying the surface of the bare silica nanoparticles with (3-aminopropyl)triethoxysilane (APTES), polyethylene glycol amine, APTES with sulfobetaine, and polyethylene glycol amine with sulfobetaine. Nanoparticle characterization, curcumin release, and measurement of protein corona inhibition were performed after incubation in the human plasma and MTT assay to confirm the stability and efficiency of the nanoparticles. Results: The presence of the sulfobetaine group could influence the curcumin loading capacity of the silica nanoparticles. The results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated no significant protein adsorption on the curcumin-loaded, zwitterionic-coated nanoparticles compared to the other nanoparticles. In addition, the MTT assay confirmed the cytotoxicity of the curcumin-loaded sulfobetaine-APTES-silica nanoparticles on MCF-7 cancer cells.Conclusion: Our findings confirmed the effects of the zwitterionic coating on the physicochemical properties of the nanoparticles. These findings play a key role in the development of novel nanoparticles for drug delivery applications.

Spreading of Cell Aggregates on Zwitterion-Modified Chitosan Films.

The sulfobetaine (SB) moiety, which comprises a quaternary ammonium group linked to a negatively charged sulfonate ester, is known to impart nonfouling properties to interfaces coated with polysulfobetaines or grafted with SB-polymeric brushes. Increasingly, evidence emerges that the SB group is, overall, a better antifouling group than the phosphorylcholine (PC) moiety extensively used in the past. We report here the synthesis of a series of SB-modified chitosans (CH-SB) carrying between 20 and 40 mol % SB per monosaccharide unit. Chitosan (CH) itself is a naturally derived copolymer of glucosamine and N-acetyl-glucosamine linked with a β-1,4 bond. Analysis by quartz crystal microbalance with dissipation (QCM-D) indicates that CH-SB films (thickness ∼ 20 nm) resist adsorption of bovine serum albumin (BSA) with increasing efficiency as the SB content of the polymer augments (surface coverage ∼ 15 μg cm–2 for films of CH with 40 mol % SB). The cell adhesivity of CH-SB films coated on glass was assessed by determining the spreading dynamics of CT26 cell aggregates. When placed on chitosan films, known to be cell-adhesive, the CT26 cell aggregates spread by forming a cell monolayer around them. The spreading of CT26 cell aggregates on zwitterion-modified chitosans films is thwarted remarkably. In the cases of CH-SB30 and CH-SB40 films, only a few isolated cells escape from the aggregates. The extent of aggregate spreading, quantified based on the theory of liquid wetting, provides a simple in vitro assay of the nonfouling properties of substrates toward specific cell lines. This assay can be adopted to test and compare the fouling characteristics of substrates very different from the chemical viewpoint.

Polymer electrolytes through functionalization of poly (poly (ethylene glycol) methacrylate) with zwitterionic pendant groups: The role of ion clusters upon conductivity

The present study proposes a complete (pMPS8) and partial (pMPS8-co-PEGDMA) functionalization of poly(poly(ethyleneglycol) methyl ether methacrylate (pPEGMA) with zwitterionic pendant groups to improve the mobility of polymer chains and ion-ion associations during Li+ conduction (weak electrolyte). Structural, thermal and electrochemical characterizations of the polymer electrolytes are conducted to analyze the dependence of conductivity on LiPF6 concentration. The ionic conductivity of pMPS8 (3.22 × 10−5 S cm−1 at 25 °C) in the presence of LiPF6 is due to the incorporation of the zwitterionic pendant groups into the pPEGMA. In pMPS8, a more significant interaction of Li+ with the sulfobetaine group at low LiPF6 concentrations, decreases its ion movement. While at higher salt concentrations, the saturation of sulfonate groups with Li+ makes possible its interaction with ethoxy sites, thus, increasing ionic conductivity. pMPS8 is less sensitive (i.e. ionic conductivities remain constant) to the increases of salt concentration compared to the pMPS8-co-PEGDMA (larger number of ethoxy sites per pendant groups) due to its complete functionalization (short range mobility). The ionic conductivity for pMPS8-co-PEGDMA polymer starts to be significant at molar ratios higher than 1.0: 1.0, suggesting that above this stoichiometry the interactions between zwitterion pendant groups and lithium salt become suppressed, enabling its use at higher LiPF6 concentrations. The analysis of TGA, DSC, XRD and EIS exhibit that ionic conductivity is coupled with the mobility of chains, hence the transport mechanism occurs through dynamic percolation theory where the translational dynamics of the ions depends on segmental dynamics and by renewal of hopping probabilities.

Scarless Wound Closure by a Mussel-Inspired Poly(amidoamine) Tissue Adhesive with Tunable Degradability.

Burn, trauma, and various medical conditions including bacterial infection, diabetes complication, and surgery could lead to an acute cutaneous wound and scar formation. Application of tissue glues instead of sutures could minimize the additional trauma and scar formation. Despite the countless efforts devoted to the development of high-strength tissue glues, little attention has been paid to their influence on the scar formation. Here, we report the development of a new tissue glue with excellent biocompatibility and tunable degradability for scarless wound closure. A series of catechol-containing poly(amidoamine) (CPAA) polymers were synthesized via the one-step Michael addition of dopamine and bisacrylamide. The tertiary amino group in the polymer backbone was used to introduce a zwitterionic sulfobetaine group by one-step ring-opening polymerization. The introduction of the zwitterionic sulfobetaine group could easily tune the hydrophilicity and the degradability of CPAA without influencing the density of the catechol group in the polymer. Lap-shear tests on the porcine skin demonstrated a high adhesion strength of 7 kPa at 1 h, rising to 24 kPa by 12 h. Addition of silica nanoparticles could further enhance the adhesion strength by 50%. In vivo studies further confirmed that the CPAA tissue glue could effectively accelerate the healing process of incisional wounds on the back of Sprague Dawley rats compared with suture and reduce the scar formation.

Design of a Zwitterion Polymer Electrolyte Based on Poly[poly (ethylene glycol) methacrylate]: The Effect of Sulfobetaine Group on Thermal Properties and Ionic Conduction

Polymer electrolytes are expected to play an overriding role in the development of sustainable lithium ion batteries. In this study, amorphous poly(poly(ethylene glycol) methacrylate) (pPEGMA) and pPEGMA functionalized with sulfobetaine pendants (pMPS8) are synthesized, and subsequently formulated with LiPF6 to be assessed as solid polymer electrolytes (SPE). The polymer properties are investigated using Differential scanning calorimetry (DSC), X‐ray diffraction (XRD), Attenuated total reflection Fourier transform infrared (FTIR) and Electrochemical Impedance Spectroscopy (EIS). These experimental analyses are used to account for the effects of a methacrylate‐type polymer as an alternative to improve Li+ mobility across the polymer, and synergic benefits of its functionalization with sulfobetaine groups. pPEGMA displayed a Tg around −49 °C, which increases in the presence of the lithium salt to −38 °C due to the interactions arising between Li+ ions and the polymer, as confirmed by XRD and FTIR characterizations. The ionic conductivity of the pPEGMA/LiPF6 system is 6.92 × 10−6 S cm−1, which denotes a partial dissociation of LiPF6 as a result of the formation of ion pairs, detected by the structural characterization. The functionalization of pPEGMA is an efficient method to decrease the Tg down to −53 °C, suggesting that pMPS8 keeps amorphous pPEGMA matrix allowing mobility of polymer chains by the presence of the sulfobetaine pendants. Evidence of this behavior is determined with the chemical and structural evaluations, and clearly observed in the increase of ionic conductivity by two orders of magnitude. Although the Tg of the pMPS8/LiPF6 system considerably augments to −24 °C, its effects are negligible in ionic conductivity (3.22 × 10−5 S cm−1), indicating that a relatively low stiff backbone arises in pMPS8 structures, which is not influenced by the presence of LiPF6 due to the strong charge delocalization generated by the sulfobetaine groups.

Dynamic Surface Tension of Heterogemini Surfactants with Quaternary Ammonium Salt and Gluconamide or Sulfobetaine Headgroups.

Dynamic surface tensions of two types of heterogemini surfactants with nonidentical hydrophilic headgroups consisting of a quaternary ammonium salt (cationic) and a gluconamide (nonionic) or sulfobetaine (zwitterionic) group were measured using the maximum bubble pressure method. For these compounds, effects of alkyl chain length, structure of the hydrophilic groups, and surfactant concentration were investigated using diffusion coefficients and parameter x. The parameter x is related to the difference between the energies of adsorption and desorption of the surfactant. The values of x of heterogemini surfactants increased as the alkyl chain length increased, and they were slightly larger than that for the corresponding monomeric surfactant. This is because of an increase in hydrophobicity caused by two alkyl chains, as well as interactions between two different hydrophilic groups. Adsorption rate of the heterogemini surfactants decreased with increasing alkyl chain length, indicating slow dynamics, and inhibited adsorption to the air/water interface as the chain length increased. However, at higher concentrations, the heterogemini surfactants showed rapid and effective adsorption and increased adsorption rates at higher concentrations. Diffusion coefficients of the heterogemini surfactants decreased with increasing concentrations for all chain lengths, indicating diffusion of the solute molecules to the subsurface and adsorption of the solute from the subsurface to the surface.

Novel zwitterionic polyurethanes with good biocompatibility and antibacterial activity

Zwitterionic polyurethanes show great potential applications in biomedical field. This paper reports a novel approach to prepare zwitterionic polyurethanes from N-methyldiethanolamine (MDEA), hexamethylene diisocyanate (HDI) and 1,3-propanesultone (1,3-PS). Results show that sulfobetaine groups are successfully grafted onto the MDEA based polyurethanes. The introduction of sulfobetaine group improves cell biocompatibility of polyurethanes. Moreover, good antibacterial activity of zwitterions is retained in this MDEA based polyurethanes. This work provides another substantiation to integrate antimicrobial and non-fouling properties.

A NIPAM–Zwitterion Copolymer: Rheological Interpretation of the Specific Ion Effect on the LCST

The effect of various cations and anions on the ability to shield the electrostatic interaction between charged copolymers containing a non‐ionic moiety (N‐isopropylacrylamide (NIPAM)) is explored. The Hofmeister series, first noted in 1888, ranks the relative influence of ions on the physical behavior of a wide variety of aqueous processes ranging from colloidal assembly to protein folding. The viscoelastic behavior of a poly(NIPAM‐co‐Zw10%) solution as a function of ionic strength in the presence of different ions is rheologically investigated. The obtained copolymer exhibits a thermoresponsive behavior, with tunable lower critical solution temperature (LCST) ranging from 28 to 33 °C. The viscosity change specifically demonstrates the effectiveness of the low‐molecular‐weight ions in weakening the inter‐/intramolecular electrostatic crosslinks among the sulfobetaine chain and in enhancing the hydration of the macromolecule. The effectiveness of the anions follows the Hofmeister series while that of the cations follows the reversed Hofmeister series, as demonstrated by Collins' concept of “matching water affinity,” due to presence of a sulfobetaine group in the chains. image

Probing structure–antifouling activity relationships of polyacrylamides and polyacrylates

We have synthesized two different polyacrylamide polymers with amide groups (polySBAA and polyHEAA) and two corresponding polyacrylate polymers without amide groups (polySBMA and polyHEA), with particular attention to the evaluation of the effect of amide group on the hydration and antifouling ability of these systems using both computational and experimental approaches. The influence of polymer architectures of brushes, hydrogels, and nanogels, prepared by different polymerization methods, on antifouling performance is also studied. SPR and ELISA data reveal that all polymers exhibit excellent antifouling ability to repel proteins from undiluted human blood serum/plasma, and such antifouling ability can be further enhanced by presenting amide groups in polySBAA and polyHEAA as compared to polySBMA and polyHEA. The antifouling performance is positively correlated with the hydration properties. Simulations confirm that four polymers indeed have different hydration characteristics, while all presenting a strong hydration overall. Integration of amide group with pendant hydroxyl or sulfobetaine group in polymer backbones is found to increase their surface hydration of polymer chains and thus to improve their antifouling ability. Importantly, we present a proof-of-concept experiment to synthesize polySBAA nanogels, which show a switchable property between antifouling and pH-responsive functions driven by acid–base conditions, while still maintaining high stability in undiluted fetal bovine serum and minimal toxicity to cultured cells. This work provides important structural insights into how very subtle structural changes in polymers can yield great improvement in biological activity, specifically the inclusion of amide group in polymer backbone/sidechain enables to obtain antifouling materials with better performance for biomedical applications.

Functional groups grafted nonwoven fabrics for blood filtration—The effects of functional groups and wettability on the adhesion of leukocyte and platelet

In this work, the effects of grafted functional groups and surface wettability on the adhesion of leukocyte and platelet were investigated by the method of blood filtration. The filter materials, poly(butylene terephthalate) nonwoven fabrics bearing different functional groups including hydroxyl (OH), carboxyl (COOH), sulfonic acid group (SO3H) and zwitterionic sulfobetaine group (⊕N((CH3)2)(CH2)3SO3⊖) with controllable wettability were prepared by UV radiation grafting vinyl monomers with these functional groups. Our results emphasized that both surface functional groups and surface wettability had significant effects on the adhesion of leukocyte and platelet. In the case of filter materials with the same wettability, leukocytes adhering to filter materials decreased in the order: the surface bearing OH only>the surface bearing both OH and COOH>the surface bearing sulfobetaine group>the surface bearing SO3H, while platelets adhering to filter materials decreased as the following order: the surface bearing SO3H>the surface bearing both OH and COOH>the surface bearing OH only>the surface bearing sulfobetaine group. As the wettability of filter materials increased, both leukocyte and platelet adhesion to filter materials declined, except that leukocyte adhesion to the surface bearing OH only remained unchanged.

Research and synthesis of organosilicon nonthrombogenic materials containing sulfobetaine group

A novel organosilicon sulfobetaine was synthesized through the reaction of organosilicon containing tertiary amino with 1,3-propanesulfone. Then this organosilicon sulfobetaine was coated onto polyurethane and organosilicon surface to improve their blood compatibility. The existence of sulfobetaine structure on the surface of materials was revealed by ATR-FTIR and XPS. The thermo-capability of synthesized silicone rubber, containing sulfobetaine was revealed by TGA. The blood compatibilities of organosilicon sulfobetaine and other materials such as silicone and PU as reference coated with them were evaluated by platelet-rich plasma adhesion experiment. The novel segmented silicone rubber containing sulfobetaine structure showed perfect blood compatibility.

Association of End-Functionalized Block Copolymers. Light Scattering and Viscometric Studies

The dilute solution properties of diblock and triblock copolymers of styrene and isoprene with one dipolar sulfobetaine group at either or both ends of the chain were examined in CCl 4 by static and dynamic light scattering as well as by viscometry. The copolymers were prepared by anionic polymerization techniques using [3-(dimethylamino)propyl]lithium as initiator. The tertiary amine groups were converted to sulfobetaines by reaction with cyclopropanesultone. Aggregation numbers derived from static and dynamic methods are in good agreement and decrease with increasing molecular weight of the polymeric tail. Aggregates seem to be polydisperse and stable for long periods of time