Zwitterionic Structure Research Articles

Recent Progress of Squaraine-Based Fluorescent Materials and Their Biomedical Applications

Squaraines (SQs) are unusual cyanine dyes with a unique resonance-stabilized zwitterionic structure. These dyes have attracted significant attention in the fields of organic electronics and organic photonics, due to their facile synthesis, intense and narrow visible and near-infrared absorption/emission, high photostability, low biotoxicity, etc. In this review, we summarize the recent progress of SQ-based fluorescent materials and their biomedical applications. After a brief introduction to SQs, general synthetic routes and design principles of SQ-based fluorescent materials, as well as their aggregation-induced luminescence behaviors, are discussed. Subsequently, their biomedical applications for cell imaging and as fluorescent sensors and therapeutic agents are introduced. Finally, a summary and perspective are given for promoting the development of SQs-based fluorescent materials.

Influence of zwitterionic structure design on mixed matrix membrane stability, hydrophilicity, and fouling resistance: A computational study

Zwitterion-based mixed matrix membranes (MMMs) with designed characteristics of enhanced water flux, selectivity, and fouling mitigation have emerged as a new class of advanced membranes for oilsands process-affected wastewater (OSPW) treatment. Zwitterions (ZW) characterized by super-hydrophilicity and excellent fouling resistance have gained increasing attention in membrane modification research. In general, zwitterion properties are determined by the chemistry and structural properties of its constituents, including the polymer backbone, charged moieties, spacers, as well as molecular configuration. This study used molecular dynamics simulation (MDS) to investigate the effects of polymer backbone (PB), spacer length (SL), and spacer chemistry (SC) on ZW-based MMM properties such as stability, hydrophilicity, and oil-antifouling potentiality. Membrane performance was also assessed at high temperatures (50, 70, and 90 °C. The results suggest PB, SL, and SC all influence the resultant MMM performance, with SL being the most impactful structural parameter on stability and hydrophilicity. Variation of SL was suspected to alter the ionic association and partial charges of zwitterionic moieties, which affect their ability to interact with the polymer network and water molecules. Spacer chemistry (i.e., hydroxyl (-OH) groups) can initiate self-association between zwitterionic charged groups having short SL, lessening their inter-molecular networking ability. However, for ZWs with long SL, the presence of hydroxyl groups on the spacer can result in the formation of hydrogen bonds and/or electrostatic interactions with other ZW molecules and polyvinylidene difluoride (PVDF) polymer chains or water molecules, improving membrane stability and hydrophilicity. High temperatures reduced membrane stability but to a lesser extent for MMMs compared to unmodified PVDF membrane. While temperature greatly influenced membrane hydrophilicity, the impacts were membrane-specific. The oil-fouling propensity of pristine PVDF membrane increased with temperature but of MMMs appeared stable across the temperature range studied.

Solution Equilibrium Studies on Salicylidene Aminoguanidine Schiff Base Metal Complexes: Impact of the Hybridization with L-Proline on Stability, Redox Activity and Cytotoxicity.

The proton dissociation processes of two tridentate salicylidene aminoguanidine Schiff bases (SISC, Pro-SISC-Me), the solution stability and electrochemical properties of their Cu(II), Fe(II) and Fe(III) complexes were characterized using pH-potentiometry, cyclic voltammetry and UV-visible, 1H NMR and electron paramagnetic resonance spectroscopic methods. The structure of the proline derivative (Pro-SISC-Me) was determined by X-ray crystallography. The conjugation of L-proline to the simplest salicylidene aminoguanidine Schiff base (SISC) increased the water solubility due to its zwitterionic structure in a wide pH range. The formation of mono complexes with both ligands was found in the case of Cu(II) and Fe(II), while bis complexes were also formed with Fe(III). In the complexes these tridentate ligands coordinate via the phenolato O, azomethine N and the amidine N, except the complex [Fe(III)L2]+ of Pro-SISC-Me in which the (O,N) donor atoms of the proline moiety are coordinated beside the phenolato O, confirmed by single crystal X-ray crystallographic analysis. This binding mode yielded a stronger Fe(III) preference for Pro-SISC-Me over Fe(II) in comparison to SISC. This finding is also reflected in the lower redox potential value of the iron-Pro-SISC-Me complexes. The ligands alone were not cytotoxic against human colon cancer cell lines, while complexation of SISC with Cu(II) resulted in moderate activity, unlike the case of its more hydrophilic counterpart.

Effect of amine and acid functionalization on polyimide: A structure-property relationship study

The poly(imide) (PI) based membrane plays a vital role in water purification field. Due to the absence of hydrophilic group and charged species, the PI membrane is easily attacked by water living microbial systems. This problem can be solved by the introduction of some ionic species onto PI backbone. Chemical grafting of chloroethylamine (CEA) and chloroaceticacid (CAA) onto PI was done in a single and two step processes in the presence of AlCl3 as a Friedel-Crafts (FC) catalyst. Thus functionalized PI was characterized by FT-IR, 1H NMR, DSC, TGA, SEM, WCA, EDX, XPS, XRD and POM. The antibacterial and antifungus properties of PI4 system were tested. The FT-IR spectrum showed a small peak at 1623 cm−1 due to the zwitter ionic structure. The surface morphology was slightly changed while changing the grafting agent. The simultaneous grafting of CEA and CAA onto PI yielded better results. The thermal stability of PI before and after functionalization was compared with the recent literature reports.

Zwitterions Layer at but Do Not Screen Electrified Interfaces.

The role of ionic electrostatics in colloidal processes is well-understood in natural and applied contexts; however, the electrostatic contribution of zwitterions, known to be present in copious amounts in extremophiles, has not been extensively explored. In response, we studied the effects of glycine as a surrogate zwitterion, ion, and osmolyte on the electrostatic forces between negatively charged mica–mica and silica–silica interfaces. Our results reveal that while zwitterions layer at electrified interfaces and contribute to solutions’ osmolality, they do not affect at all the surface potentials, the electrostatic surface forces (magnitude and range), and solutions’ ionic conductivity across 0.3–30 mM glycine concentration. We infer that the zwitterionic structure imposes an inseparability among positive and negative charges and that this inseparability prevents the buildup of a counter-charge at interfaces. These elemental experimental results pinpoint how zwitterions enable extremophiles to cope with the osmotic stress without affecting finely tuned electrostatic force balance.

Molecular dynamics simulation, DFT calculations and vibrational spectroscopic study of N[sbnd]H•••O bound dimer models for DL-β-phenylalanine and 3-amino-3-(4-chlorophenyl)propionic acid

Zwitterionic NH•••O bonded dimer structures have been proposed one each for DL-β-Phenylalanine and 3-Amino-3-(4-chlorophenyl)propionic acid. Stable zwitterionic monomer possessing NH3+ and COO¯ moieties in implicit aqueous solvation were computed at B3LYP/6-311++G** level and used for classical MD simulations. MD simulations yielded, among many NH•••O bonded transient dimer and trimer species, the two dimer structures with longest lifetime τ in water medium (τ = 111.67 ps for DL-β-Phenylalanine and 111.53 ps for 3-Amino-3-(4-chlorophenyl)propionic acid). The first peaks in radial distribution functions (RDF) confirmed the formation of NH•••O bonded dimer structures, one each for DL-β-Phenylalanine and 3-Amino-3-(4-chlorophenyl)propionic acid; the first minima determined the cut-off values for the inter-molecular H•••O distances. Further, the first minimum-solvation shell also indicated one zwitterionic dimer structure with 10 water molecules as solvent medium. Experimental IR frequencies due to the NH3+ and COO¯ moieties agree within 5% of the computed values for the dimer structures. Low-frequency Raman bands near 100–50 cm−1 are assigned to the torsional vibration modes of zwitterionic NH•••O bonded dimer structures. On the role of Chlorine with respect to all the molecular properties of 3-Amino-3-(4-chlorophenyl)propionic acid vs DL-β-Phenylalanine computed from NBO, AIM and NCI calculations, its influence is not substantial but discernible enough for gaining insights into the two NH•••O bonded zwitterionic dimer species.

Zwitterionic Ammonium Sulfonate Polymers: Synthesis and Properties in Fluids.

Polymer zwitterions continue to emerge as useful materials for numerous applications, ranging from hydrophilic and antifouling coatings to electronic materials interfaces. While several polymer zwitterion compositions are now well established, interest in this field of soft materials science has grown rapidly in recent years due to the introduction of new structures that diversify their chemistry and architecture. Nonetheless, at present, the variation of the chemical composition of the anionic and cationic components of zwitterionic structures remains relatively limited to a few primary examples. In this article, the versatility of 4-vinylbenzyl sultone as a precursor to ammonium sulfonate zwitterionic monomers, which are then used in controlled free radical polymerization chemistry to afford "inverted sulfobetaine" polymer zwitterions, is highlighted. An evaluation of the solubility, interfacial activity, and solution configuration of the resultant polymers reveals the dependence of properties on the selection of tertiary amines used for nucleophilic ring-opening of the sultone precursor, as well as useful properties comparisons across different zwitterionic compositions.

Substituent, Solvent, and Dispersion Effects on the Zwitterionic Character and Dimerization Thermochemistry of the Group 6 Fulvene Metal Tricarbonyl Complexes.

Dimerizations of fulvene metal tricarbonyl complexes of the type (C5H4CRR')M(CO)3 (R, R' = MeO, Me, H; M = Cr, Mo, W) to form a metal-metal bond and a new carbon-carbon bond, thereby giving binuclear cyclopentadienyl metal carbonyl derivatives, are predicted to be thermochemically favored but to have significant activation energies ranging from ΔE = 19 to 42 kcal/mol. However, the introduction of dimethylamino but not methoxy substituents onto the exocyclic carbon atom changes the situation drastically so that the monomers [C5H4CH(NMe2)]M(CO)3 and [C5H4C(NMe2)2]M(CO)3 become strongly thermochemically favored, lying ΔE = 43 kcal/mol (M = W) to 63 kcal/mol (M = Cr) below their corresponding dimers. In such dimethylamino-substituted (fulvene)M(CO)3 derivatives, the M-C distance to the exocyclic fulvene carbon is lengthened beyond the bonding distance to give a zwitterionic structure with a pentahapto fulvene ligand. Such M-C distances in (fulvene)M(CO)3 complexes, which have preferred zwitterionic structures, increase with increasing solvent polarity (i.e., dielectric constant) until a saturation point is reached.

Superprotonic conduction of intrinsically zwitterionic microporous polymers based on easy-to-make squaraine, croconaine and rhodizaine dyes.

Porous organic polymers (POPs) have been prepared via a novel metal free polycondensation between a tritopic indole-based monomer and squaric, croconic and rhodizonic acids. Each of the three POPs exhibited high BET surface areas (331–667 m2 g−1) and zwitterionic structures. Impedance measurements revealed that the intrinsic POPs were relatively weak proton conductors, with a positive correlation between the density of oxo-groups and the proton conduction. Doping the materials with LiCl vastly improved the proton conductivity up to a value of 0.54 S cm−1 at 90 °C and 90% relative humidity.

Probing the Structure of Moxifloxacin and Norfloxacin by Density Functional Theory and Raman Spectroscopy-=SUP=-*-=/SUP=-

In the present work, structures of two fluoroquinolone molecules namely Moxifloxacin and Norfloxacin are investigated using density functional theory and the Raman spectroscopy. The density functional theory calculation with B3LYP-6-31+G(d,p) level of theory reveals several structures of two molecules. The low energy stable structures of Moxifloxacin show multiple intramolecular H-bonds which could be responsible for the stabilization of these structures, however, the orientation of the (4aS, 7aS)-hexahydro-1H-pyrrolo[3,4-b]pyridin (hpb) ring determines the most stable structure. In Norfloxacin, the orientation of the ethyl group in the plane perpendicular to the ring frame determines the most stable structure whereas, the orientation of piperazine ring is critical for the determination of stable structure of the Norfloxacin zwitterion. Complexes of most stable structures of Moxifloxacin and Norfloxacin with one and two water molecules were also calculated. The Raman spectra were calculated for low energy structures of Moxifloxacin and Norfloxacin and also for their complexes with one and two water molecules. The experimental Raman spectra were obtained on powder sample of two molecules utilizing our lab-built Raman spectroscopy setup. The experimental Raman spectra were analyzed in light of the calculated Raman spectra of neutral molecules and their complexes with water. It was found that, in the powder form, the Raman spectra of two molecules can be better explained if intermolecular H-bonding with water molecules is considered. The study, therefore, confirms the hygroscopic nature of two molecules under ambient environment. Keywords: Moxifloxacin, Norfloxacin, density functional theory, Raman spectroscopy.

Imine-based Zwitterion: Synthesis, single-crystal characterization, and computational investigation

The 2‑hydroxy-1-naphthaldehyde based Schiff base zwitterions: (E)-1-(((4-methoxyphenyl)-iminio)methyl)naphthalen-2-olate (3a) and (E)-1-(((2‑methoxy-4-nitrophenyl)iminio)methyl)-naphthalen-2-olate (3b) have been obtained from the condensation reaction of 2‑hydroxy-1-naphthaldehyde and substituted aniline. The structures of these Schiff base zwitterions have been verified unambiguously by the single-crystal X-ray diffraction analysis. The SC-XRD (single crystal X-ray diffraction) exploration revealed that both compounds have same crystal system, i.e., monoclinic, and same space group, i.e., P21/c. Also, there are intermolecular attractive forces that are responsible for the stabilization of these organic frameworks. Additionally, these structures have been thoroughly explored by the density functional theory (DFT) calculations. The optimized geometries were found to be close to the experimental structures. The analysis of frontier molecular orbitals (FMOs) suggested that 3a would be more stable towards redox reactions than 3b. Therefore, modifying the imine-zwitterion structure with the nitro group and changing the position of methoxy group would increase the reactivity of the resulting species. This is further supported by the computed global reactivity parameters (GRPs): both compounds should be considered as noticeably stable, both from thermodynamic and kinetic points of view, with 3a showing even higher stability. The compound 3b was shown to be more reactive in redox processes, being more prone to be reduced rather than oxidized. The higher stability of 3a was further supported by the NBO analysis results.

Local Spatial Polarization Induced Efficient Charge Separation of Squaraine‐Linked COF for Enhanced Photocatalytic Performance

AbstractThe efficiencies of semiconductor photocatalysis are always severely restricted by the rapid recombination of charge carriers in the bulk phase, while local polarization is an efficient scenario to conquer the above issue to boost the photocatalytic performance. Here, as a proof‐of‐concept demonstration, local charge polarization induced by the intrinsic zwitterionic resonance structure of photocatalysts is reported. A novel squaraine‐based covalent organic framework (SQ‐COF‐1) photocatalyst with an interesting zwitterionic resonance structure is creatively developed. Meanwhile, the comparison samples (SQ‐COF‐2 and PDA‐COF) based on similar COF structure with tunable local polarity are accordingly designed and prepared. The local charge polarization generated from the zwitterionic resonance structure profoundly redistributes and separates the charge carriers, as evidenced by experimental and theoretical results collectively. Benefiting by the largest local polarization, SQ‐COF‐1 exhibits superior visible‐light‐driven photocatalytic activities than SQ‐COF‐2, PDA‐COF, and commonly used polymeric carbon nitride photocatalyst. This work presents a local charge polarization protocol for engineering charge behavior to promote photocatalysis, which shows great promise for the future design of high‐performance photocatalytic materials.

Delafloxacin, Finafloxacin, and Zabofloxacin: Novel Fluoroquinolones in the Antibiotic Pipeline.

Novel antimicrobial agents, approved for clinical use in past years, represent potential treatment options for various infections. In this review, we summarize the most important medical and microbiological features of three recently approved fluoroquinolones, namely delafloxacin, finafloxacin, and zabofloxacin. Delafloxacin possesses an anionic chemical structure, and represents broad-spectrum activity, as it targets both bacterial DNA gyrase and topoisomerase IV enzymes of gram-positive and gram-negative bacteria with equal affinity. Its molecular surface is larger than that of other fluoroquinolones, and it has enhanced antibacterial efficacy in acidic environments. Delafloxacin has been approved to treat acute bacterial skin and skin-structure infections, as well as community-acquired bacterial pneumonia. Finafloxacin has a zwitterionic chemical structure, and targets both DNA gyrase and topoisomerase IV enzymes. This enables a broad antibacterial spectrum; however, finafloxacin has so far only been approved in ear-drops to treat bacterial otitis externa. Zabofloxacin is also a broad-spectrum fluoroquinolone agent, and was first approved in South Korea to treat acute bacterial exacerbation of chronic obstructive pulmonary disease. The introduction of these novel fluoroquinolones into daily practice extends the possible indications of antibiotics into different bacterial infections, and provides treatment options in difficult-to-treat infections. However, some reports of delafloxacin resistance have already appeared, thus underlining the importance of the prudent use of antibiotics.

An investigation on the structure and group vibrations of balenine molecule by matrix isolation IR spectroscopy, DFT and MP2 based calculations

Stable conformers of neutral balenine were scanned through molecular dynamics simulations and energy minimizations using Allinger’s MM2 force field. For each of the found minimum-energy conformers, geometry optimization and thermochemistry calculations were performed by using B3LYP, MP2, G3MP2B3 methods, 6-31G(d), 6–311++G(d,p) and aug-cc-pvTZ basis sets. The calculation results have indicated that balenine has about twenty stable conformers whose relative energies are in the range of 0–9.5 kcal/mol. Three of these are thought to provide the major contribution to matrix isolation IR spectra of the molecule. Our solvent calculations using the polarized continuum model revealed the stable zwitterion structures which are predicted to dominate IR spectra of balenine in water and heavy water (D2O) solvents. Pulay’s SQM-FF method was used in scaling of the harmonic force constants and vibrational spectral data calculated for the neutral and zwitterion structures. These refined calculation data together with those obtained from anharmonic frequency calculations enabled us to correctly interpret the matrix isolation IR spectrum of balenine and the tautomerism-based changes observed in its KBr IR and solution (D2O) IR spectra. The results revealed the crucial role of conformation and zwitterionic tautomerism on the structure and vibrational spectral data of the molecule.

Theoretical Investigation of Glycine Micro-Solvated. Energy and NMR Spin Spin Coupling Constants Calculations

Glycine in its neutral form can exist in the gas phase while its zwitterion form is more stable in water solution, but how many waters are actually necessary to stabilize the zwitterionic structure in the gas phase? Are the intramolecular isotropic spin spin coupling constants sensitive enough to accuse the change in the environment? or the conformer observed? These and related questions have been investigated by a computational study at the level of density functional theory employing the B3LYP functional and the 6-31++G**-J basis set. We found that at least two water molecules explicitly accounted for in the super-molecule structure are necessary to stabilize both conformers of glycine within a water polarizable continuum model. At least half of the SSCCs of both conformers are very stable to changes in the environment and at least four of them differ significantly between Neutral and Zwitterion conformation.

Visualizing Aβ deposits in live young AD model mice with a simple red/near-infrared-fluorescent AIEgen

Precise and early detection of β-amyloid (Aβ) deposits in situ and in real time is pivotal to the diagnosis and early intervention of Alzheimer’s disease (AD). Optical imaging stands out to be a promising technique for such a task; however, it still remains a big challenge, due to the lack of high-performance imaging contrast agent. Restricted by poor blood-brain barrier (BBB) penetrability, short-wavelength excitation and emission, as well as the aggregation-caused quenching effect, the widely used gold-standard probes cannot be used for early in-vivo imaging of Aβ deposits. Herein, we integrate the Aβ deposits-favored geometry, amphiphilic and zwitterionic molecular structure, extended D-π-A electronic structure, and 3D conformation into one molecule, facilely establishing a simple and economic imaging contrast agent that enjoys high specificity and affinity to Aβ deposits, good BBB penetrability, bright red/near-infrared fluorescence, low interference from autofluorescence, aggregation-induced emission (AIE) feature, high signal-to-noise ratio (SNR), and high contrast. In-vitro, ex-vivo, and in-vivo experiments with different strains of mice indicate that AIE-CNPy-AD holds the universality to Aβ deposits identification. Noteworthily, AIE-CNPy-AD is even able to precisely trace the small and sparsely-distributed Aβ deposits in AD model mice as young as 4-month-old APP/PS1 mice, the youngest having Aβ deposits. Moreover, the present probe could clearly reveal the increase and enlargement of Aβ deposits as the mice grow. Therefore, AIE-CNPy-AD might be an ideal alternative for early AD diagnosis and highly reliable monitoring of AD progression.

8-Hydroxyquinoline-Amino Acid Hybrids and Their Half-Sandwich Rh and Ru Complexes: Synthesis, Anticancer Activities, Solution Chemistry and Interaction with Biomolecules.

Solution chemical properties of two novel 8-hydroxyquinoline-D-proline and homo-proline hybrids were investigated along with their complex formation with [Rh(η5-C5Me5)(H2O)3]2+ and [Ru(η6-p-cymene)(H2O)3]2+ ions by pH-potentiometry, UV-visible spectrophotometry and 1H NMR spectroscopy. Due to the zwitterionic structure of the ligands, they possess excellent water solubility as well as their complexes. The complexes exhibit high solution stability in a wide pH range; no significant dissociation occurs at physiological pH. The hybrids and their Rh(η5-C5Me5) complexes displayed enhanced cytotoxicity in human colon adenocarcinoma cell lines and exhibited multidrug resistance selectivity. In addition, the Rh(η5-C5Me5) complexes showed increased selectivity to the chemosensitive cancer cells over the normal cells; meanwhile, the Ru(η6-p-cymene) complexes were inactive, most likely due to arene loss. Interaction of the complexes with human serum albumin (HSA) and calf-thymus DNA (ct-DNA) was investigated by capillary electrophoresis, fluorometry and circular dichroism. The complexes are able to bind strongly to HSA and ct-DNA, but DNA cleavage was not observed. Changing the five-membered proline ring to the six-membered homoproline resulted in increased lipophilicity and cytotoxicity of the Rh(η5-C5Me5) complexes while changing the configuration (L vs. D) rather has an impact on HSA or ct-DNA binding.

Diradicals or Zwitterions: The Chemical States of m -Benzoquinone and Structural Variation after Storage of Li Ions

Diradicals or Zwitterions: The Chemical States of <i>m</i> -Benzoquinone and Structural Variation after Storage of Li Ions

Zwitterionic triple-network hydrogel electrolyte for advanced flexible zinc ion batteries

Aqueous zinc ion battery (ZIB) is auspicious for wearable energy storage devices due to its low cost and high safety. For ZIBs to meet the flexibility and mechanical properties desirable for wearable electronics, it is imperative to develop a lithely high-performance electrolyte material with good tensile and compressible strength to withstand the electrochemical reactions. In this work, we rationally fabricated a novel zwitterionic triple-network structure hydrogel electrolyte of polyacrylamide (PAM)/gelatin/[2-methylacryloxy) ethyl]dimethyl-(3-sulfonic acid propyl) ammonium hydroxide (DMAPS) for flexible textile-based ZIBs. Apart from the excellent flexibility and mechanical stability, the zwitterionic triple-network hydrogel electrolyte also ensured high ionic conductivity and enhanced Zn2+ transference number. As expected, the symmetric cell with such electrolyte acquired a cycle stability of over 400 h. Additionally, the corresponding flexible ZIBs delivered a stable capacity of 175 mAh·g−1 for 100 cycles at 500 mA g−1 with excellent Coulombic efficiency of over 99%. The fabricated battery can even light a 2 V bulb under heavy weight pressure of 500 g or in any bending state. Therefore, this work provides a simple yet industrially scalable approach to the commercial fabrication of flexible ZIBs.

Fluorinated Polymer Zwitterions: Choline Phosphates and Phosphorylcholines.

Among zwitterionic structures, the choline phosphate (CP) group is uniquely attractive for its ability to access novel chemical compositions that embed functional groups directly into the zwitterionic moiety. This paper describes the attachment of fluorinated alkyl groups to CP moieties, yielding zwitterionic monomers 1 and 2 that proved amenable to controlled free radical polymerization and the production of a new set of CP-containing fluorinated polymers and copolymers with phosphorylcholine (PC) zwitterions. This combination of fluorinated hydrocarbons and zwitterions affords novel, water-soluble polymeric amphiphiles that we have examined at fluid interfaces, as coatings, in cell culture, and in magnetic resonance imaging.