Zwitterionic Compounds Research Articles

1,3‐Dipolar versus Nucleophilic Reactivity of Diaziridines Based on 3,4‐Dihydroisoquinoline toward Aryl Iso(thio)cyanates

AbstractUnsubstituted and 1‐methyl‐substituted 1,3,4,8b‐tetrahydrodiazirino[3,1‐a]isoquinolines (diaziridines 1 and 2) demonstrate different reactivities toward aryl isocyanates and aryl isothiocyanates. Diaziridine 1 reacts with aryl isocyanates as a nucleophile to afford novel 1,5,6,10b‐tetrahydro[1,2,4]triazolo[5,1‐a]isoquinolines. The addition of a Lewis or Brønsted acid switches the reaction pathway, producing seven‐membered 2,3‐benzodiazepines. In reactions of diaziridine 1 with aryl isothiocyanates, unusual zwitterionic compounds – 2‐thioxo‐5,6‐dihydro‐2H‐[1,2,4]triazolo[5,1‐a]isoquinolin‐1‐ium‐3‐ides – and products of the addition of two molecules of diaziridine 1 to one molecule of aryl isothiocyanate are obtained. However, in reactions with aryl iso(thio)cyanates under heating or acid catalysis, diaziridine 2 is first converted into an azomethine imine, the 1,3‐dipolar cycloaddition of which to the dipolarophile produces substituted triazolo[5,1‐a]isoquinolin‐2(3H)‐(thi)ones. Proposed is a new method for azomethine imine generation from diaziridine 2 enabled by Brønsted acid catalysis. Antitumour activity of select compounds obtained was assayed to help guide future drug discovery efforts.

Influence of Starch on the Structure-Properties Relationship in Polyethylene Glycol/Polycaprolactone Diol Polyurethanes.

Improvements in the antithrombogenicity activity of biomaterials for cardiovascular applications are necessary to meet the demand for vascular grafts in the world. Zwitterionic compounds tend to be used due to their anti-fouling properties, which reduce platelet adhesions and protein absorptions. Therefore, in this research, potato starch (AL-N) and zwitterionic starch (AL-Z) (obtained by Williamson etherification) were included as fillers in polyurethane (PU) matrices from polycaprolactone diol (PCL), polyethylene glycol (PEG), pentaerythritol (PE) and isophorone diisocyanate (IPDI) in order to study their effect in terms of their physicochemical, mechanical and thermal properties. We conducted our evaluation using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), contact angle analysis, swelling behavior, thermogravimetric analysis (TGA), tensile/strain analysis, scanning electron microscopy equipped with energy dispersive X-ray spectroscopy (SEM-EDS), dynamic mechanic analysis (DMA), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The results showed that AL-N and AL-Z modified these properties, where AL-N improved tensile strength, and AL-Z increased the hydrophilicity of polyurethanes matrices; additionally, AL-N had interactions with the soft segments, and AL-Z had interactions with the hard segments. Finally, both fillers reduced the degree of crystallinity and did not affect the thermal stability of polyurethanes.

Development of potent non-acylhydrazone inhibitors of intestinal sodium-dependent phosphate transport protein 2b (NaPi2b)

Inhibition of intestinal sodium-dependent phosphate transport protein 2b (NaPi2b), responsible for intestinal phosphate absorption, is considered to reduce serum phosphate levels, making it a promising therapeutic approach for hyperphosphatemia. Previously, we aimed to identify new drugs for hyperphosphatemia treatment and obtained zwitterionic compound 3 (IC50 = 64 nM) as a potent selective inhibitor of intestinal NaPi2b. This small-molecule compound is gut-restricted owing to its almost membrane-impermeable property. However, when compound 3, containing an acylhydrazone structure, is exposed to plasma, it is easily metabolized and likely produces an acetylhydrazine compound. Clinical studies have shown that acetylhydrazine is a risk factor for hepatic toxicity owing to its microsomal metabolism, wherein toxic reactive intermediates are formed.Therefore, in this study, we aimed to obtain potent NaPi2b inhibitors without an acylhydrazone structure to reduce the risk of hepatic toxicity. We developed compound 18, an anilide compound with zwitterionic property having potent phosphate uptake inhibitory activity in vitro (IC50 = 14 nM) and low bioavailability (FaFg = 5.9%). Oral administration of compound 18 in rats showed a reduction in phosphate absorption comparable to that observed with lanthanum carbonate, a clinically effective phosphate binder used in hyperphosphatemia treatment. Moreover, combined administration of compound 18 and lanthanum carbonate resulted in an additive effect on phosphate absorption inhibition in rats. Our findings suggest that combination therapy with lanthanum carbonate and compound 18 will not only provide better treatment outcomes for hyperphosphatemia but also reduce gastrointestinal side effects in patients.

Synthesis and the Antimicrobial Activity of Salt Carbenoid Compounds

Aim. To synthesize aliphatic and aromatic derivatives of salt carbenoid compounds of the series of imidazole, benzimidazole, pyridine, pyrimidine and 1,3,4-oxadiazole containing fluorophenyl, cetyl or adamantyl substituents, and study their antimicrobial (antibacterial and antifungal) activities.Results and discussion. New derivatives of heterocyclic carbenoid salts and zwitterions based on the imidazole, benzimidazole, pyridine, pyrimidine and 1,3,4-oxadiazole heterocyclic systems containing fluorophenyl, cetyl or adamantyl substituents were synthesized. For this purpose, reactions of cyclization of the corresponding diimines with ethoxymethyl chloride (imidazolium salts), quaternization of the corresponding azoles with cetyl bromide or 1-adamantyl bromide in organic solvents (benzimidazolium, pyridinium and 1,3,4-oxadiazolium salts), cyclization of di(1-adamantylamino)alkanes hydrobromides with the orthoformic ester (4,5-dihydroimidazolium and tetrahydropyridinium salts) were used. Zwitterionic compounds were obtained by the reaction of the corresponding azolium salts with phenyl isothiocyanate in the presence of potassium carbonate. Some macrocyclic and adamantyl substituted heterocyclic compounds showed antifungal and antibacterial activities.Experimental part. The structure of the compounds synthesized was proven by 1H and 13C NMR spectroscopy methods. The antimicrobial activity was studied out by the agar diffusion method to determine diameters of the growth inhibition zones of microorganisms (bacteria and fungi) and by the method of serial dilutions to determine the minimum inhibitory concentration and minimum bactericidal and fungicidal concentrations.Conclusions. The synthesis of new heterocyclic carbenoid salts and zwitterions based on the imidazole, benzimidazole, pyridine, pyrimidine and 1,3,4-oxadiazole heterocyclic systems containing fluorophenyl, cetyl or adamantyl substituents has been performed. Compounds of macrocyclic and adamantyl heterocyclic series with antifungal and antibacterial activities have been found. 1,3-Dicetylimidazolium bromide, macrocyclic bis(decylenebenzimidazolium) bromides, azolium-N-phenylthiocarboximides have been proven to be the most active.

Back-Contact Ionic Compound Engineering Boosting the Efficiency and Stability of Blade-Coated Perovskite Solar Cells.

Surface defect passivation, which plays a vital role in achieving high-efficiency perovskite solar cells (PSCs) in a spin-coating process, is rarely compatible with a printing process. Currently, printing PSCs with high efficiency remains a challenge, as only a few laboratories realized an efficiency of over 20%. In this work, zwitterionic compounds 2-hydroxyethyl trimethyl ammonium chloride (HETACl) and butyltrimethylammonium chloride (BTACl) were introduced, both of which can spontaneously adsorb on the surface perovskite and form an ultrathin passivation layer by a dip coating method. The complex formed by the strong interaction of HETACl with MAI on the surface of the perovskite film leads to the formation of a rough perovskite surface, which affects the enhancement of device performance. BTACl with a chemically inert side chain induces a weak interaction with the perovskite. It is demonstrated that BTACl not only passivates surface defects of the perovskite but also heals the grain boundaries and results in more uniform crystallizations. Finally, PSCs upon BTACl treatment were blade-coated in an ambient environment with a relative humidity of <50%, which produced a champion efficiency of 20.5% with negligible hysteresis, and the active area of the cell device was 0.095 cm2. After being stored in air for 30 days, unencapsulated PSCs treated with BTACl retained 95% of their initial efficiency, which is far superior to that of the control and those treated with HETACl.

Ovataline: A Polyketide Isolated from the Benthic Dinoflagellate Ostreopsis cf. ovata with 5α-Reductase Inhibitory Activity in RWPE-1 Prostatic Cells

Ovataline (1), which is a polar metabolite containing a hexahydroquinoline moiety, was isolated from cultures of the marine dinoflagellate Ostreopsis cf. ovata. 1 was characterized as a zwitterionic compound with hexahydroquinoline and tetrahydropyran rings. The configurations of the chiral centers in 1 were established using ROESY correlations, J-based configurational and Mosher reaction analyses, and density functional theory calculations. 1 exhibited a 78% (1 μM) inhibition of type II 5α-reductase in testosterone propionate-induced RWPE-1 human prostatic cells.

Ultrafiltration Membranes Functionalized with Copper Oxide and Zwitterions for Fouling Resistance.

Polymeric membrane fouling is a long-standing challenge for water filtration. Metal/metal oxide nanoparticle functionalization of the membrane surface can impart anti-fouling properties through the reactivity of the metal species and the generation of radical species. Copper oxide nanoparticles (CuO NPs) are effective at reducing organic fouling when used in conjunction with hydrogen peroxide, but leaching of copper ions from the membrane has been observed, which can hinder the longevity of the CuO NP activity at the membrane surface. Zwitterions can reduce organic fouling and stabilize NP attachment, suggesting a potential opportunity to combine the two functionalizations. Here, we coated polyethersulfone (PES) ultrafiltration membranes with polydopamine (PDA) and attached the zwitterionic compound, thiolated 2-methacryloyloxyethyl phosphorylcholine (MPC-SH), and CuO NPs. Functionalized membranes resulted in a higher flux recovery ratio (0.694) than the unfunctionalized PES control (0.599). Copper retention was high (>96%) for functionalized membranes. The results indicate that CuO NPs and MPC-SH can reduce organic fouling with only limited copper leaching.

Exploring the Reactivity of B-Connected Carboranylphosphines in Frustrated Lewis Pair Chemistry: A New Frame for a Classic System.

The primary phosphines MesPH2 and tBuPH2 react with 9‐iodo‐m‐carborane yielding B9‐connected secondary carboranylphosphines 1,7‐H2C2B10H9‐9‐PHR (R=2,4,6‐Me3C6H2 (Mes; 1 a), tBu (1 b)). Addition of tris(pentafluorophenyl)borane (BCF) to 1 a, b resulted in the zwitterionic compounds 1,7‐H2C2B10H9‐9‐PHR(p‐C6F4)BF(C6F5)2 (2 a, b) through nucleophilic para substitution of a C6F5 ring followed by fluoride transfer to boron. Further reaction with Me2SiHCl prompted a H−F exchange yielding the zwitterionic compounds 1,7‐H2C2B10H9‐9‐PHR(p‐C6F4)BH(C6F5)2 (3 a, b). The reaction of 2 a, b with one equivalent of R'MgBr (R’=Me, Ph) gave the extremely water‐sensitive frustrated Lewis pairs 1,7‐H2C2B10H9‐9‐PR(p‐C6F4)B(C6F5)2 (4 a, b). Hydrolysis of the B−C6F4 bond in 4 a, b gave the first tertiary B‐carboranyl phosphines with three distinct substituents, 1,7‐H2C2B10H9‐9‐PR(p‐C6F4H) (5 a, b). Deprotonation of the zwitterionic compounds 2 a, b and 3 a, b formed anionic phosphines [1,7‐H2C2B10H9‐9‐PR(p‐C6F4)BX(C6F5)2]−[DMSOH]+ (R=Mes, X=F (6 a), R=tBu, X=F (6 b); R=Mes, X=H (7 a), R=tBu, X=H (7 b)). Reaction of 2 a, b with an excess of Grignard reagents resulted in the addition of R’ at the boron atom yielding the anions [1,7‐H2C2B10H9‐9‐PR(p‐C6F4)BR’(C6F5)2]− (R=Mes, R’=Me (8 a), R=tBu, R’=Me (8 b); R=Mes, R’=Ph (9 a), R=tBu, R’=Ph (9 b)) with [MgBr(Et2O) n ]+ as counterion. The ability of the zwitterionic compounds 3 a, b to hydrogenate imines as well as the Brønsted acidity of 3 a were investigated.

Binary and ternary solutions of zwitterionic compounds: theoretical and spectral studies

Theoretical bases of the solvent influence on the electronic spectra of binary and ternary solutions of some zwitterionic compounds are discussed. Three cycloimmonium ylids were investigated as spectrally active zwitterionic compounds. The energetic and electro-optical parameters of the studied molecules were obtained by using Spartan´14 programs. Some linear dependences between the wavenumbers in the maxima of the electronic spectra of the studied compounds and the solvent parameters are established. The value of the excited state dipole moment and its orientation relative to the ground state dipole moment are established based on the theories regarding the solvent influence on the electronic absorption spectra. The difference between the interaction energies in molecular pairs: ylid-solvent (1) and ylid-solvent (2) is estimated based on the statistical cell model of ternary solutions. These studies offer information about the composition of the first molecular shell surrounding the spectrally active molecules and about the nature and strength of the interactions between these molecules and their neighboring shell. Most of the ylid reactions take place in situ and from this point of view the knowledge regarding their reactivity and their interactions with solvents are very important.

Electrochemical Detection of Glucose and Lactate Dehydrogenase Using a Zwitterionic Phenazine Compound as an Electron Mediator for NADH Oxidation

AbstractPhenazine compounds have been used as simple organic catalysts for the rapid oxidation of NADH. Although positively charged phenazine compounds are highly water‐soluble, their uncharged, reduced forms are not. We report the use of a zwitterionic phenazine compound, 3‐(1‐methoxyphenazin‐5‐ium‐5‐yl)propane‐1‐sulfonate (mPPS), as an organic catalyst and electron mediator for the electrochemical oxidation of NADH and detection of glucose and lactate dehydrogenase (LDH). mPPS is highly stable in phosphate buffered saline (pH 7.4). Furthermore, the negatively charged, reduced form of mPPS is highly water‐soluble. The detection limits of glucose and LDH in artificial serum were approximately 0.02 mM and 2 ng/mL, respectively.

Facile zwitterionization of polyvinylidene fluoride microfiltration membranes for biofouling mitigation

Styrene maleic anhydride (SM) is a commercially available copolymer able to react with diamines. The ring-opening reaction results in the formation of a zwitterionic compound of prime interest to the development of fouling-resistant membranes. To this end, we designed microfiltration antifouling polyvinylidene fluoride (PVDF) membranes by blending PVDF with a copolymer obtained from the reaction of SM with N,N-dimethylamino-1,3-propanediamine, and then by inducing phase inversion of the casting solution from the vapor phase. The resulting membranes possess excellent surface and bulk hydrophilicity, compared to the pristine membrane. Besides, as adding copolymer shifts the zeta potential closer to electroneutrality, biofouling is alleviated, as tested in static conditions with Escherichia coli , blood cells or bovine serum albumin. Filtration of a bacterial solution also demonstrated the superior performances of the as-prepared membrane to those of a commercial hydrophilic PVDF membrane, with a higher flux recovery ratio (90% vs. 65%) and lower irreversible flux decline ratio (10% vs. 32%). Given also the stability of the design and the low costs involved in the making of the membranes (all materials are commercially available and inexpensive), the present membranes are suitable alternatives to commercial hydrophilic PVDF membranes, but with better fouling mitigation. • The facile zwitterionization of a commercial copolymer is introduced. • The zwitterionic copolymer is solubilized with polyvinylidene fluoride. • Stable zwitterionic bi-continuous are fabricated. • Effective anti-biofouling property is demonstrated with various biofoulants.

A zwitterionic salt with one sulfonate and two ether functional groups as an additive for lithium-ion battery electrolyte

An imidazolium-based zwitterionic compound bearing two ether groups at the C-1 and C-2 positions and one sulfonate group at the C-3 position of the imidazolium ring was successfully synthesized. The compound was characterized using nuclear magnetic resonance spectroscopy and elemental analysis. The product (2.5 wt%) was added to a commercial electrolyte for lithium-ion batteries containing 1 M LiPF6 in ethylene carbonate, dimethyl carbonate, and ethyl methyl carbonate (1:1:1 by volume). The resulting electrolyte had a slightly higher ionic conductivity in the range 10–70 °C than the model electrolyte, implying that the additive had a beneficial impact, possibly due to the C-2 rather than the C-1 ether group. Cyclic voltammetry analysis indicated that the electrochemical stability of the electrolyte did not change. The effect of the electrolyte additive on the cell’s 1C cycling performance was also examined: it was found that a stable discharge capacity was maintained for up to 100 cycles. Fourier transform infrared spectra of complexes formed by the synthesized product and LiPF6 at different ratios showed that the Li+ ions interacted with all the functional groups.

Extensive Phytochemical Assessment of Dendrobium fimbriatum Hook (Orchidaceae)

Dendrobium fimbriatum Hook is an important medicinal and ornamental orchid that may lead to important drugs and cosmetics. In this study, 2 analytical strategies were combined to describe the detailed composition of a hydroethanolic extract of the whole plant. The CARAMEL approach, based on centrifugal partition chromatography and nuclear magnetic resonance data interpretation, allowed the rapid dereplication of 21 major constituents, mainly including polyols, nucleosides, zwitterionic compounds, phenolic compounds, and organic acids. Further semipreparative high-performance liquid chromatography and spectroscopic analyses led to the isolation of 6 additional compounds; 4 phenanthrenes (plicatol B, hircinol, plicatol A, and plicatol C), 1 bibenzyl (3′,4-dihydroxy-3,5′-dimethoxybibenzyl), and 1 furostanol saponin (protodioscin), as well as a new phenanthrene derivative, plicatol D. A total of 28 metabolites were structurally elucidated, among which 23 are described for this species for the first time.

Experimental and molecular dynamics studies of zwitterionic inhibitors of methane hydrate dissociation

Hydrate dissociation inhibitors can be widely applied in the field of natural gas exploitation. A combined experimental and molecular dynamics study into a new type of hydrate dissociation inhibitor is presented herein. The polymeric kinetic inhibitor is zwitterionic and was characterized by Fourier transform infrared spectroscopy and thermogravimetric analysis. When evaluated by methane hydrate formation and dissociation tests, the zwitterionic compound showed an inhibitory effect on hydrate dissociation of up to 37.3%. A kinetic model for the hydrate dissociation process in the presence of hydrate dissociation inhibitors was validated by the experimental data. The difference in dissociation efficiency can be represented by the methane diffusion coefficient in the liquid phase. Molecular dynamics simulations were performed to investigate the effect of the inhibitor on methane hydrate and water molecules. The results showed that the charged functional groups improved the interaction energy between the inhibitor and methane hydrate through Coulomb interactions, and the sulfonate group had a strong hydration ability, which could affect the distribution of water molecules in the water phase. The molecular-level understanding of the dissociation inhibition mechanism is instructional for the design of new and effective hydrate dissociation inhibitors.

Synthesis of Polyanionic Cellulose Carbamates by Homogeneous Aminolysis in an Ionic Liquid/DMF Medium.

Polyanionic cellulose carbamates were synthesized by rapid and efficient homogeneous aminolysis of cellulose carbonate half-esters in an ionic liquid/DMF medium. Cellulose bis-2,3-O-(3,5-dimethylphenyl carbamate), as a model compound, reacted with different chloroformates to cellulose carbonates. These intermediates were subjected to aminolysis, for which both the reactivity of different chloroformates towards C6-OH and the reactivity/suitability of the respective carbonate half-ester in the aminolysis were comprehensively studied. Phenyl chloroformate and 4-chlorophenyl chloroformate readily reacted with C6-OH of the model cellulose derivative, while 4-nitrophenyl chloroformate did not. The intermediate 4-chlorophenyl carbonate derivative with the highest DS (1.05) was then used to evaluate different aminolysis pathways, applying three different amines (propargyl amine, β-alanine, and taurine) as reactants. The latter two zwitterionic compounds are only sparingly soluble in pure DMF as the typical reaction medium for aminolysis; therefore, several alternative procedures were suggested, carefully evaluated, and critically compared. Solubility problems with β-alanine and taurine were overcome by the binary solvent system DMF/[EMIM]OAc (1:1, v/v), which was shown to be a promising medium for rapid and efficient homogeneous aminolysis and for the preparation of the corresponding cellulose carbamate derivatives or other compounds that are not accessible by conventional isocyanate chemistry. The zwitterionic cellulose carbamate derivatives presented in this work could be promising chiral cation exchangers for HPLC enantiomer separations.

Dopamine Assisted Self-Cleaning, Antifouling, and Antibacterial Coating via Dynamic Covalent Interactions.

The rapid accumulation of dead bacteria or protein on a bactericidal surface can reduce the effectiveness of the modified surface and alter its biocidal activity by shielding the surface biocide functional groups, promoting microbial attachment and subsequent biofilm formation. Thus, the alteration of biocidal activity due to biofilm formation can cause serious trouble including severe infection or implant or medical device failure leading to death. Therefore, developing a smart self-cleaning surface is of great interest. Ideally, such a surface can not only kill the attached microbials but also release the dead cells and foulants from the surface under a particular incitement on demand. In this project, a sugar-responsive self-cleaning coating has been developed by forming covalent boronic ester bonds between catechol groups from polydopamine and a benzoxaborole pendant from zwitterionic and cationic polymers. To incorporate antifouling properties and enhance the biocompatibility of the coating, bioinspired zwitterionic compound 2-methacryloyloxyethyl phosphorylcholine (MPC) was chosen and benzoxaborole pendant containing zwitterionic polymer poly(MPC-st-MAABO) (MAABO: 5-methacrylamido-1,2-benzoxaborole) was synthesized. Additionally to impart antibacterial properties to the surface, a quaternary ammonium containing cationic polymer poly(2-(methacryloyloxy)ethyl trimethylammonium (META)-st-MAABO)) was synthesized. These synthesized polymers were covalently grafted to a polydopamine (PDA) coated surface by forming a strong cyclic boronic ester complex with a catechol group of the PDA layer endowing the surface with bacteria contact-killing properties and capturing specific protein. After the addition of cis-diol containing competitive molecules, i.e., saccharides/sugars, this boronic ester complex with a catechol group of PDA was replaced and the attached polymer layer was cleaved from the surface, resulting in the release of both absorbed protein and live/killed bacteria electrostatically attached to the polymer layer. This dynamic self-cleaning surface can be a promising material for biomedical applications avoiding the gathering of dead cells and debris that are typically encountered on a traditional biocidal surface.

Zwitterionic polysiloxane-polyamide hybrid active layer for high performance and chlorine resistant TFC desalination membranes

• Zwitterionic polysiloxane-PA hybrid active layer TMC on the PS support layer was prepared. • SPPT was synthesized by the reaction of DMAPS with 1,3-propane sulfone. • Chlorine resistance of fabricated membrane increased from 2 h to 6 h. • Salt rejection slightly increased from 98.8% to 98.9%. Hybrid polysiloxane-polyamide thin-film composite (TFC) reverse osmosis (RO) membranes were produced in the presence of a zwitterionic silane compound during polyamide active layer preparation by interfacial polymerization for an enhanced desalination performance and chlorine resistance. The zwitterionic functional silane monomer, (3-sulfopropylbetaine-propyl)-trimethoxysilane (SPPT), was added to an aqueous m-phenylenediamine (MPD) monomer solution at different concentrations; 0.05, 0.1, 0.25, 0.5 and 1.0 SPPT/MPD ratios. The aqueous monomer solutions adsorbed on a polysulfone support layer were contacted with an organic trimesoyl chloride (TMC) monomer solution to create a polysiloxane-polyamide hybrid active layer by interfacial polymerization. Hybrid active layers were characterized by scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), water contact angle (WCA), and zeta potential measurements. Membranes produced with a SPPT/MPD ratio of 0.1 exhibited an increase in permeate flux from 25 L m −2 h −1 to 33 L m −2 h −1 (55 bar operating pressure; 3.2% NaCl feed) while the salt rejection was not compromised, but slightly increased from 98.8% to 98.9%, when compared to the control membrane prepared without SPPT. The highest resistance against chlorine was observed for the membranes produced with a SPPT/MPD ratio of 1.0, for which, a significant membrane damage and consequent loss of salt rejection were observed after six hours of exposure to chlorine solution, while the control membrane was prone to chlorine damage after two hours.

Discovery of Gut-Restricted Small-Molecule Inhibitors of Intestinal Sodium-Dependent Phosphate Transport Protein 2b (NaPi2b) for the Treatment of Hyperphosphatemia.

NaPi2b is primarily expressed in the small intestine, lungs, and testes and plays an important role in phosphate homeostasis. The inhibition of NaPi2b, responsible for intestinal phosphate absorption, is considered to reduce serum phosphate levels, making it a promising therapeutic approach for hyperphosphatemia. Using a novel phosphate uptake inhibitor 3 (IC50 = 87 nM), identified from an in-house compound collection in human NaPi2b-transfected cells as a prototype compound, we conducted its derivatization based on a Ro5-deviated strategy to develop orally administrable small-molecule NaPi2b inhibitors with nonsystemic exposure. Consequently, compound 15, a zwitterionic compound with a potent in vitro phosphate uptake inhibitory activity (IC50 = 64 nM) and a low membrane permeability (Pe < 0.025 × 10-6 cm/s), was developed. Compound 15 showed a low bioavailability (F = 0.1%) in rats and a reduction in phosphate absorption in the rat intestinal loop assay comparable to sevelamer hydrochloride, a clinically effective phosphate binder for treating hyperphosphatemia.

Catalytic applications of zwitterionic transition metal compounds.

This frontiers article highlights recent developments on the application of transition metal-based zwitterionic complexes in catalysis. Recent applications of selected zwitterionic catalysts in polymerization reactions, including the carbonylative polymerization of cyclic ethers, carbon-carbon coupling reactions, the asymmetric hydrogenation of unfunctionalized olefins, and the hydrofunctionalization of alkenes are reviewed. In addition, advances in the field of hydrogenation/dehydrogenation reactions related to energy applications, including the hydrogenation of CO2 and the dehydrogenation of formic acid and N-heterocycles, the functionalization of CO2 with amines and hydrosilanes, and the valorization of polyfunctional bio-based feedstocks, such as the dehygrogenation of glycerol to lactic acid or the reduction of levulinic acid into γ-valerolactone, are also described.

Improvement of the filtration and antifouling performance of a nanofibrous sterile membrane by a one-step grafting zwitterionic compound

A zwitterionic NFM was employed as a sterile membrane for an absolute interception of 107 cfu cm−2Brevundimonas diminuta.