Zwitterionic Characteristics Research Articles

Vanadium(V) complexes derived from triphenylphosphonium and hydrazides: cytotoxicity evaluation and interaction with biomolecules.

The development of coordination compounds with antineoplastic therapeutic properties is currently focused on non-covalent interactions with deoxyribonucleic acid (DNA). Additionally, the interaction profiles of these compounds with globular plasma proteins, particularly serum albumin, warrant thorough evaluation. In this study, we report on the interactions between biomolecules and complexes featuring hydrazone-type imine ligands coordinated with vanadium. The potential to enhance the therapeutic efficiency of these compounds through mitochondrial targeting is explored. This targeting is facilitated by the derivatization of ligands with triphenylphosphonium groups. Thus, this work presents the synthesis, characterization, interactions, and cytotoxicity of dioxidovanadium(V) complexes (C1-C5) with a triphenylphosphonium moiety. These VV-species are coordinated to hydrazone-type iminic ligands derived from (3-formyl-4-hydroxybenzyl)triphenylphosphonium chloride ([AH]Cl) and aromatic hydrazides ([H2L1]Cl-[H2L5]Cl). The structures of the five complexes were elucidated through single-crystal X-ray diffraction and vibrational spectroscopies, confirming the presence of dioxidovanadium(V) species in various geometries with degrees of distortion (τ = 0.03-0.50) and highlighting their zwitterionic characteristics. The molecular structural stability of C1-C5 in solution was ascertained using 1H, 19F, 31P, and 51V-nuclear magnetic resonance. Moreover, their interactions with biomolecules were evaluated using diverse spectroscopic methodologies and molecular docking, indicating moderate interactions (Kb ≈ 104 M-1) with calf thymus DNA in the minor groove and with human serum albumin, predominantly in the superficial IB subdomain. Lastly, the cytotoxic potentials of these complexes were assessed in keratinocytes of the HaCaT lineage, revealing that C1-C5 induce a reduction in metabolic activity and cell viability through apoptotic pathways.

Amplified Spontaneous Emission from Zwitterionic Excited-State Intramolecular Proton Transfer.

The unique four-level photocycle characteristics of excited-state intramolecular proton transfer (ESIPT) materials enable population inversion and large spectral separation between absorption and emission through their respective enol and keto forms. This leads to minimal or no self-absorption losses, a favorable feature in acting as an optical gain medium. While conventional ESIPT materials with an enol-keto tautomerism process are widely known, zwitterionic ESIPT materials, particularly those with high photoluminescence, are scarce. Facilitated by the synthesis and characterization of a new family of 2-hydroxyphenyl benzothiazole (HBT) with fluorene substituents, HBT-Fl1 and HBT-Fl2, we herein report the first efficient zwitterionic ESIPT lasing material (HBT-Fl2). The zwitterionic ESIPT HBT-Fl2 not only shows a remarkably low solid-state amplified spontaneous emission (ASE) threshold of 5.3 μJ/cm2 with an ASE peak at 609 nm but also exhibits high ASE photostability. Coupled with its substantially large Stokes shift (≈236 nm ≈10,390 cm-1) and an extremely small overlap of excited-state absorption with ASE emission, comprehensive density functional theory (DFT) and time-dependent DFT studies reveal the zwitterionic characteristics of HBT-Fl2. In opposition to conventional ESIPT with π-delocalized tautomerism as observed in analogue HBT-Fl1 and parent HBT, HBT-Fl2 instead shows charge redistribution in the proton transfer through the fluorene conjugation. This structural motif provides a design tactic in the innovation of new zwitterionic ESIPT materials for efficient light amplification in red and longer-wavelength emission.

Basic Amino Acids Modulated Neutral-pH PEDOT:PSS for Stable Blue Perovskite Light-Emitting Diodes.

State-of-the-art external quantum efficiencies (EQEs) have exceeded 20% for near-infrared, red, and green perovskite light-emitting diodes (PeLEDs) so far. Nevertheless, the cutting-edge blue counterparts demonstrate an inferior device performance, which impedes the commercialization and industrialization of PeLEDs in ultrahigh-definition displays. As the most popular hole transport layer, poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) bears the acidic and hygroscopic drawbacks, which deteriorates the device efficiency and long-term stability of blue PeLEDs. In this work, the basic amino acids with zwitterionic characteristics are proposed to modulate the pH of PEDOT:PSS, which are arginine, lysine, and histidine. It is found that they play a triple function to the blue perovskite films: modulating the acidity of PEDOT:PSS, controlling the crystalline process, and passivating the defects at the PEDOT:PSS/perovskite interface. As a result, the utilization of neutral PEDOT:PSS leads to a significant enhancement in stability and photoluminescence quantum yield. Eventually, the pure-blue PeLEDs achieve a record EQE of 5.6% with the emission peak at 467 nm. This research proves that the interfacial engineering of hole transport layers is a reliable strategy to enhance the device efficiency and operation stability of blue PeLEDs.

Use of a new zwitterionic cellulose derivative for removal of crystal violet and orange II from aqueous solutions

This study describes the synthesis of a new bioadsorbent with zwitterionic characteristics and its successful application for removal of a cationic dye (crystal violet, CV) and an anionic dye (orange II, OII) from single component aqueous systems. The new bi-functionalized cellulose derivative (MC3) was produced by chemical modification of cellulose with succinic anhydride and choline chloride to introduce carboxylic and quaternary ammonium functional groups on the cellulose surface. MC3 was characterized by several wet chemical and spectroscopic methods. The effects of solution pH, contact time, and initial solute concentration on removal of CV and OII by MC3 were investigated. Studies of the desorption and re-adsorption of the dyes were also carried out. The isotherms for adsorption of CV and OII on MC3 were satisfactorily fitted using the Konda and Langmuir models. MC3 showed experimental maximum adsorption capacities of 2403 mg g-1 for CV and 201 mg g-1 for OII. The desorption and re-adsorption results showed that MC3 could be reused in successive adsorption cycles, which is essential for minimizing process costs and waste generation. The findings showed that MC3 is a versatile biosorbent capable of efficiently removing both cationic and anionic dyes.

Species-Specific Urothelial Toxicity With an Anti-HIV Noncatalytic Site Integrase Inhibitor (NCINI) Is Related to Unusual pH-Dependent Physicochemical Changes.

GS-9695 and GS-9822 are next-generation noncatalytic site integrase inhibitors (NCINIs) with significantly improved potency against human immunodeficiency virus compared with previous drugs such as BI-224436. Development stopped due to vacuolation of the bladder urothelium seen in cynomolgus monkey but not in rat; this lesion was absent in equivalent preclinical studies with BI-224436 (tested in dog and rat). Lesions were unlikely to be attributable to target because NCINIs specifically target viral integrase protein and no mammalian homologue is known. Secondary pharmacology studies, mitochondrial toxicity studies, immunophenotyping, and analysis of proteins implicated in cell-cell interactions and/or bladder integrity (E-cadherin, pan-cytokeratin, uroplakins) failed to offer any plausible explanation for the species specificity of the lesion. Because it was characterized by inflammation and disruption of urothelial morphology, we investigated physicochemical changes in the bladder of cynomolgus monkey (urinary pH 5.5-7.4) that might not occur in the bladder of rats (urinary pH 7.3-8.5). In measurements of surface activity, GS-9822 showed an unusual transition from a monolayer to a bilayer at the air/water interface with decreasing pH, attributed to the strong association between drug molecules in adjacent bilayer leaflets and expected to be highly disruptive to the urothelium. Structural analysis of GS-9822 and GS-9695 showed zwitterionic characteristics over the range of pH expected in cynomolgus monkey but not rat urine. This exotic surface behavior is unlikely with BI-224436 since it would transition from neutral to cationic (never zwitterionic) with decreasing pH. These data provide useful insights to guide discovery and development of NCINIs, related compounds, and zwitterions.

Liquid crystalline and rheological properties of chitin whiskers with different chemical structures and chargeability

The liquid crystalline and rheological properties of chitin whiskers (CHWs) are significant for their application in fabrication of highly ordered composite materials and optical components. The aim of this work was to elucidate the influence of chemical structure and chargeability (zeta potential, electropositivity, electronegativity or zwitterionic character) on the liquid crystalline and rheological properties of CHWs. Firstly, CHWs with different chemical structure, including positively charged whiskers (CHWs and CHWs-D/60 min) and negatively charged whiskers (mCHWs), were designed via acid hydrolysis, deacetylation, and maleation, respectively. Subsequently, the chargeability of the above whiskers was further regulated by protonation or deprotonation. The whisker aqueous suspensions with high zeta potential behaved as nematic liquid crystals or chiral nematic liquid crystals, whereas those with low zeta potential had no liquid crystal characteristics. The viscosity, G', and G" values of the CHWs and CHWs-D/60 min aqueous suspensions treated with protonation were lower than those of the corresponding whiskers treated with deprotonation. However, the mCHWs exhibited different changes in their rheological properties under protonation or deprotonation due to the electronegativity and zwitterionic characteristics. In addition, the effects of ionic strength and pH on the liquid crystalline and rheological properties of CHWs, CHWs-D/60 min, and mCHWs aqueous suspensions varied since the chemical structure and chargeability of whiskers differ.

Expansion of primitive human hematopoietic stem cells by culture in a zwitterionic hydrogel

The ability to expand hematopoietic stem and progenitor cells (HSPCs) ex vivo is critical to fully realize the potential of HSPC-based therapies. In particular, the application of clinically effective therapies, such as cord blood transplantation, has been impeded because of limited HSPC availability. Here, using 3D culture of human HSPCs in a degradable zwitterionic hydrogel, we achieved substantial expansion of phenotypically primitive CD34+ cord blood and bone-marrow-derived HSPCs. This culture system led to a 73-fold increase in long-term hematopoietic stem cell (LT-HSC) frequency, as demonstrated by limiting dilution assays, and the expanded HSPCs were capable of hematopoietic reconstitution for at least 24 weeks in immunocompromised mice. Both the zwitterionic characteristics of the hydrogel and the 3D format were important for HSPC self-renewal. Mechanistically, the impact of 3D zwitterionic hydrogel culture on mitigating HSPC differentiation and promoting self-renewal might result from an inhibition of excessive reactive oxygen species (ROS) production via suppression of O2-related metabolism. HSPC expansion using zwitterionic hydrogels has the potential to facilitate the clinical application of hematopoietic-stem-cell therapies.

Novel mussel-inspired zwitterionic hydrophilic polymer to boost membrane water-treatment performance

Although the polyvinylidene fluoride (PVDF) membranes have been widely used for commercial water treatment, the fouling problem adversely affects the membrane deploying longevity, which can be alleviated by the facile surface segregation technology. However, the long-term stability of surface segregation modifiers (SSMs) in membrane is still a challenging issue because the inherent hydrophilicity makes SSMs to slowly dissolve in water. To improve the long-term stability of SSMs and boost the PVDF membrane performance for water treatment, a versatile catechol containing poly (ethylene glycol) modifier with zwitterionic characteristics (SZ-PEG) was synthesized and blended with PVDF to construct PVDF/SZ-PEG membranes with excellent fouling-resistance via surface segregation during non-solvent induced phase separation (NIPS). The incorporation of SZ-PEG endows the membrane with a high porosity through the reduced thermodynamic stability of casting solutions, enhancing the pure water flux of novel SSM modified membrane by 423% compared to the pristine PVDF membrane. Interestingly, the hydrophilic catechol groups in the SZ-PEG polymer accumulate on the membrane surface, resulting in both a high flux recovery ratio (FRR) of ∼96.9% and a good bovine serum albumin (BSA) rejection rate of ∼93.8%. The long-term stability of SZ-PEG polymers in the PVDF/SZ-PEG membrane is proven for 30 day incubation. The interesting findings may offer new insight into surface manipulation of PVDF/SZ-PEG membranes which is particularly effective in tuning the surface characteristics for drug delivery because of their excellent biocompatibility.

Tuning biological properties of poly (vinyl alcohol) with amino acids and studying its influence on osteoblastic cell adhesion

A new class of bio composite materials for orthopedic applications were prepared by blending polyvinyl alcohol (PVA) with certain amino acids (AA) such as glycine, lysine and phenyl alanine followed by in-situ cross-linking with citric acid (CT). CT cross-linked PVA offers sufficient chemical, thermal, and morphological stability by establishing intermolecular interaction. These biocomposite films were characterized for mechanical and thermal behaviors as well as analyzed through SEM, TGA and AFM studies. Zwitterionic characteristics of AA create cell-adhesive hydrophilic domains that act as potential cell-adhesion sites and facilitate osteointegration. Biocompatibility studies proved that PVA-AA/CT is non-toxic and exhibits good anti-bacterial activity. In-vitro bioactivity test and cell adhesion results predict that presence of AA is advantageous to enhance apatite growth and promote cell-substrate binding through modulating cellular activity of PVA polymer. Hydrophilicity of AA zwitterions significantly facilitates cell-substrate binding and CA cross-linking helps osteoblastic integration of PVA-AA/CT bio composite films. The rational design of microstructure with zwitterionic-hydrophilic domains is a key to enhance cell-substrate interaction of PVA-AAs/CT bio composites.

Ion-in-Conjugation: Squaraine as an Ultrasensitive Ammonia Sensor Material.

An organic thin-film gas sensor based on squaraine detects ammonia as low as 40 ppb with impressive reversibility and stability. The resonance-stabilized zwitterionic characteristics offer squaraines high affinity and sensitivity toward electron-rich analytes without irreversible chemical binding, while the embedded squaric ring makes SA-CH3 highly sensitive. The symmetric molecular geometry and good crystallinity also contribute to the high performance.

Application of a new bifunctionalized chitosan derivative with zwitterionic characteristics for the adsorption of Cu2+, Co2+, Ni2+, and oxyanions of Cr6+ from aqueous solutions: Kinetic and equilibrium aspects

This study describes the synthesis of a new chitosan derivative (C2) with zwitterionic characteristics and its use for the removal of cationic species Cu2+, Co2+, and Ni2+ and anionic species of Cr6+ in a single aqueous solution. The new adsorbent was synthesized by quaternization of the amine group of chitosan and esterification of hydroxyl groups with EDTA dianhydride. These combined reactions gave both cationic and anionic characteristics to C2 with the release of quaternary ammonium groups and carboxylic groups. The capacity of C2 to adsorb Cu2+, Co2+, Ni2+, and oxyanions of Cr6+ was evaluated in a batch process with different contact times, pH values, and initial concentrations. Adsorption isotherms were best fitted to the Langmuir and Sips models. The maximum adsorption capacities (Qmax) of C2 for adsorption of Cu2+, Co2+, Ni2+, and Cr6+ were 0.698, 1.125, 0.725, and 1.910mmol/g, respectively. The ΔadsG° values were in the range from −20 to −28kJ/mol. These values suggest a mixed mechanism controlling adsorption. Desorption studies using an aqueous solution consisting of 0.1mol/L HNO3 were carried out. The reusability of the recovered C2 adsorbent after desorption was also evaluated.

Lysozyme binding to tethered bilayer lipid membranes prepared by rapid solvent exchange and vesicle fusion methods

Tethered bilayer lipid membranes (tBLMs) are important tools for studying protein-lipid interactions. The widely used methodology for the preparation of these membranes is the fusion of phospholipid vesicles from an aqueous medium onto an anchored phospholipid layer. The preparation of phospholipid vesicles is a long and tedious procedure. There is another simple method, rapid solvent exchange, for preparing lipid membranes. However, there is a lack of information on the effects of the preparation method of tBLMs on their interactions with proteins. Therefore, we present in this paper a comparative study on the binding of lysozyme onto tBLMs prepared by the abovementioned methods. The prepared tBLMs have either zwitterionic or anionic characteristics. The results show that lysozyme binding onto the prepared tBLMs is unaffected by the preparation method of the tBLMs, suggesting that the tedious fusion method might be replaced by the simple rapid solvent exchange method without altering the level of protein-lipid interactions.

Synthesis of Highly Stretchable, Mechanically Tough, Zwitterionic Sulfobetaine Nanocomposite Gels with Controlled Thermosensitivities

Novel nanocomposite (NC) gels with zwitterionic characteristics were prepared by in situ free-radical polymerization of sulfobetaine monomers in the presence of exfoliated clay platelets in aqueous media. Two specific sulfobetaine monomers, N,N-dimethyl(acrylamidopropyl)ammonium propanesulfonate and butanesulfonate, were selected on the basis of the interactions between the monomers and clay, which result in uniform aqueous solutions of low viscosity and gel formation without using an organic cross-linker. The resulting NC gels with polymer–clay network structures were insoluble in NaCl solution or hot water, unlike conventional physically cross-linked gels. Also, NC gels with high mechanical properties and well-controlled thermosensitivities were effectively prepared by copolymerization with a small amount of N,N-dimethylacrylamide. The copolymer NC gels were uniform and simultaneously showed high stretchability, tough mechanical properties, and well-defined upper critical solution temperature (UCST) pha...

A zwitterionic metal–organic framework with free carboxylic acid sites that exhibits enhanced hydrogen adsorption energies

Metal–organic frameworks (MOFs) are permanently porous, crystalline materials and promising hydrogen sorbents. However, the H2 heats of adsorption are generally too small to promote significant adsorption under desired storage conditions. Increasing the H2–framework interaction energy is a prominent goal of current MOF design. Hydrogen binds to MOFs through a variety of interactions, such as dispersion, charge–induced-dipole, charge–quadrupole, and even chemical bonding. To date, these interactions have been enhanced by incorporating strongly charged groups into the MOF structures, but the effects tend to be short-range and only effective at low loadings. In this work we report the structures and H2 storage properties of two zwitterionic MOFs. These structures feature zwitterionic characteristics arising from N-heterocyclic azolium groups in the linkers and negatively charged Zn2(CO2)5 nodes. These groups exhibit net charges of +0.5 and −1.0, respectively, and interact strongly with the H2 quadrupole. Isosteric heats of adsorption of up to 7.0 kJ mol−1 are observed in these zwitterionic MOFs.

Zwitterionic polyethersulfone ultrafiltration membrane with superior antifouling property

A novel kind of zwitterionic polymer, tertiary amine- modified PES (TA-PES), bearing cationic tertiary amine groups and anionic sulfonic groups, was synthesized in this study. The as-synthesized TA-PES was employed to fabricate ultrafiltration membranes by phase inversion in a wet process using pure water or sodium chloride aqueous solution as coagulation bath. It was found that the as-fabricated ultrafiltration membranes exhibited distinct ion-strength-dependent flux due to the inherent zwitterionic characteristics of TA-PES. The permeation flux of TA-PES membranes can be varied dramatically by simply changing the ionic content in coagulation bath. Furthermore, TA-PES membranes displayed superior anti-protein-fouling property and desirable ultrafiltration performance.

Steric and electrostatic interactions govern nanofiltration of amino acids

Crossflow nanofiltration experiments were performed to investigate the factors influencing the removal of amino acids by a commercially available polymeric thin-film composite membrane. The removals of five monoprotic (Ala, Val, Leu, Gly, and Thr), one diprotic (Asp), and one dibasic (Arg) amino acids in a range of permeate fluxes, feed pH values, and ionic strengths were analyzed using a phenomenological model of membrane transport. At any given pH and ionic strength, reflection coefficients (rejection at asymptotically infinite flux) of monoprotic amino acids increased with molar radius demonstrating the role of steric interactions on their removal. Additionally, consistent with Donnan exclusion, higher reflection coefficients were obtained when the membrane and the amino acids both carried the same nature of charge (positive or negative). In other words, both co-ion repulsion and molecular size determined amino acids removal. Importantly, the removal of effectively neutral amino acids were significantly higher than neutral sugars and alcohols of similar size demonstrating that even near their isoelectric point, zwitterionic characteristics preclude them from being considered as strictly neutral.

Experimental Probe for Hyperconjugative Resonance Contribution in Stabilizing the Singlet State of 2,2-Dialkoxy-1,3-diyls: Regioselective 1,2-Oxygen Migration

A detailed study of the regioselectivity of 1,2-oxygen migration was conducted using the unsymmetrically substituted singlet 2,2-dialkoxy-1,3-diarylcyclopentane-1,3-diyls 5. The alkoxy group selectively migrates to the electron-donating p-methoxyphenyl-substituted carbon. The regioselective migration of oxygen clearly indicates a hyperconjugative resonance structure, that is, zwitterionic characteristics, in singlet 2,2-dialkoxy-1,3-diyls. This represents the first attempt to experimentally probe the contribution of hyperconjugation to stabilizing the singlet state.

Plasma Co‐Polymerisation of Two Strongly Interacting Monomers: Acrylic Acid and Allylamine

AbstractSummary: Plasma co‐polymerisation presents an exciting opportunity to produce coatings with mixtures of functional species that are difficult to achieve from single monomer systems. Unfortunately, the complexity of reactions in the plasma environment can make it difficult to predict and characterise the coating chemistries. In this study, X‐ray photoelectron (XP) and near edge X‐ray absorption fine structure (NEXAFS) spectroscopy have been used to examine coatings prepared by the co‐polymerisation of allylamine and acrylic acid. As expected, a mixture of chemical groups including amines, nitriles, amides and acids were identified. Significantly, the copolymers showed strong evidence of protonated amine (based on the N 1s XP spectra) and carboxylate anions (based on the NEXAFS O K edge); species that were not evident in coatings produced from the individual parent monomers. The results suggest that as the two monomers mix in the gas phase, allylammonium acrylate salts form and may act as a third monomer during the plasma polymerisation. The results also indicated that the addition of acrylic acid monomer suppressed the dehydrogenation of amines to nitriles and increasing the proportion of nitrogen as amine species at the interface. We speculate that these coatings will exhibit zwitterionic characteristics in aqueous solution and that they may find utility in the isoelectric focussing and separation of proteins from solution. magnified image

Electrodeposition of Iron Group-Rare Earth Alloys from Aqueous Media

Binary iron group (IG)-rare earth (RE) and ternary IG-RE-B alloys were codeposited from aqueous chloride and sulfamate solutions containing glycine as the complexing agent. The effects of solution composition and deposition conditions on deposit composition, coercivity, and morphology were investigated using dc and pulse current electrodeposition, resulting in nanocrystalline deposits approaching amorphism (grain size, ∼5 nm). Continuing research indicates substantially increased RE deposit contents have been achieved with modifications in solution composition and ratios of IG and RE to glycine with applied mA cm−2 and vigorous agitation; e.g., CoSm deposits containing 15-18 atom % Sm have been obtained. A mechanism for the codeposition of the alloys is proposed. It involves hetero-nuclear glycinato coordination complexes as a result of the zwitterionic characteristics of glycine. The complexes adsorbed on the cathode provide step-wise reduction of the depositing metals with surface adsorbed H atoms and/or direct electron transfer, resulting in alloy deposits. © 2004 The Electrochemical Society. All rights reserved.

In vitro skin permeation and retention of 5-aminolevulinic acid ester derivatives for photodynamic therapy

In photodynamic therapy (PDT), 5-aminiolevulinic acid (5-ALA) applied topically is converted, via the heme cycle, into protoporphyrin IX (PpIX), a photosensitizing agent, which upon excitation with light can induce tumor destruction. Due to its hydrophilic and zwitterionic characteristics, 5-ALA has limited penetration into the skin. More lipophilic 5-ALA ester derivatives are expected to cross stratum corneum more easily than 5-ALA. According to the determination of the partition coefficients of 5-ALA methyl, n-butyl, n-hexyl and n-octyl esters, these compounds showed an increased affinity to the SC, with 5-ALA hexyl ester and 5-ALA-octyl ester having the highest partition coefficients. Our in vitro skin permeation studies demonstrated an increased permeated amount for hexyl-ALA after 6 h of incubation, compared to other esters and 5-ALA. After 6 h, more 5-ALA-hexyl ester and -octyl ester were retained at viable epidermis and dermis than 5-ALA. According to these results, and considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, it can be supposed that topical use of ester derivatives with longer chains (C 6 or C 8) is an interesting proposal to optimize topical 5-ALA-PDT