Quaternary Amino Research Articles

Functional derivatives of chitosan, soluble in neutral medium as drugs and genetic material carrier: preparation and properties

Method of chitosan modification, providing controlled addition of the quaternized block has been proposed. The structure of the products obtained were studied by FT-IR and NMR spectroscopy; their solubility and acid-base properties was characterized by turbodimetry and potentiometry, respectively. Presence about 50% of quaternized amino groups was shown to be necessary to obtain soluble products. The difference in pH-sensitivity of modified derivatives with different types of quaternized block attachment was revealed by studying their interaction with a model polystyrene sulfonate anion. The possibility of preparing complexes based on the obtained derivatives with DNA — polyplexes, stable under conditions close to physiological ones has been demonstrated. It was shown the presence of primary amino groups on the polycation chains leads to a decrease in the polyplexe size. The data obtained can form the basis for development of drug and genetic material delivery system. The 2-stage method of chitosan modification providing controlled addition of the quaternized block has been proposed. The structure of the products obtained were studied by FT-IR and NMR spectroscopy; their solubility and acid-base properties was characterized by turbodimetry and potentiometry, respectively. The presence about 50% of quaternized amino groups was shown to be necessary to obtain soluble products. The difference in pH-sensitivity of modified derivatives with different types of quaternized block attachment was revealed by studying their interaction with a model polystyrene sulfonate anion. The possibility of preparing complexes based on the obtained derivatives with DNA, polyplexes stable under conditions close to physiological ones has been demonstrated. It is shown that the presence of primary amino groups on the polycation chains leads to a decrease in the polyplexe size. The data obtained can form the basis for development of drug and genetic material delivery systems.

An Evaluation of the Corrosion Inhibition Performance of Chitosan Modified by Quaternary Ammonium Salt for Carbon Steel in Stone Processing Wastewater.

Chitosan was used as the raw material. A quaternization reaction was carried out between 2,3-epoxypropyltrimethylammonium chloride and water-soluble chitosan to prepare quaternary ammonium salt water-soluble chitosan (QWSC), and its corrosion inhibition performance against the corrosion of carbon steel in stone processing wastewater was evaluated. The corrosion inhibition efficiencies of QWSC on carbon steel in stone processing wastewater were investigated through weight loss, as well as electrochemical and surface morphology characterization techniques. The results show that QWSC has superior corrosion inhibition performance for A3 carbon steel. When an amount of 60 mL·L-1 is added, the corrosion inhibition efficiency can reach 59.51%. Electrochemical research has shown that a QWSC inhibitor is a mixed-type corrosion inhibitor. The inhibition mechanisms of the QWSC inhibitor revealed that the positive charge on the surface of carbon steel in stone wastewater was conducive to the adsorption of Cl- in the medium, which produced an excessive negative charge on the metal's surface. At the same time, the quaternary ammonium cation and amino cation formed in QWSC in stone processing wastewater can be physically absorbed on the surface of A3 carbon steel, forming a thin-film inhibitor to prevent metal corrosion.

Synergistic Pd/Cu Catalysis for the Synthesis of Unnatural Quaternary Amino Acids

Synergistic Pd/Cu Catalysis for the Synthesis of Unnatural Quaternary Amino Acids

Discovery and Characterization of Pyridoxal 5'-Phosphate-Dependent Cycloleucine Synthases.

Pyridoxal 5'-phosphate (PLP)-dependent enzymes are the most versatile biocatalysts for synthesizing nonproteinogenic amino acids. α,α-Disubstituted quaternary amino acids, such as 1-aminocyclopentane-1-carboxylic acid (cycloleucine), are useful building blocks for pharmaceuticals. In this study, starting with the biosynthesis of fusarilin A, we discovered a family of PLP-dependent enzymes that can facilitate tandem carbon-carbon forming steps to catalyze an overall [3 + 2]-annulation. In the first step, the cycloleucine synthases use SAM as the latent electrophile and an in situ-generated enamine as the nucleophile for γ-substitution. Whereas previously characterized γ-replacement enzymes protonate the resulting α-carbon and release the acyclic amino acid, cycloleucine synthases can catalyze an additional, intramolecular aldol or Mannich reaction with the nucleophilic α-carbon to form the substituted cyclopentane. Overall, the net [3 + 2]-annulation reaction can lead to 2-hydroxy or 2-aminocycloleucine products. These studies further expand the biocatalytic scope of PLP-dependent enzymes.

Metal-Free One-Pot Domino Synthesis of Oxazolidinethione Derivatives of Quaternary Amino Acids from α-Amino Esters and Aldehydes Using CS2.

We present a streamlined, metal-free, one-pot domino approach to efficiently synthesize oxazolidinethione derivatives containing substituted quaternary amino acids. This method employs α-amino esters, aldehydes, and CS2 under mild conditions, constructing three new bonds (C-N, C-C, and C-O) to produce oxazolidinethione compounds featuring a quaternary center and a beta-hydroxy derivative in high yields. This scalable protocol enables the creation of libraries of biologically significant, intricate amino acid derivatives using amino esters and aldehydes.

Cu-catalyzed asymmetric regiodivergent electrosynthesis and its application in the enantioselective total synthesis of (-)-fumimycin

Quaternary amino acids are one of the essential building blocks and precursors of medicinally important compounds. Various synthetic strategies towards their synthesis have been reported. On the other hand, developing core-structure-oriented cross-dehydrogenative coupling (CDC) reactions, is a largely unsolved problem. Herein, we describe a copper-catalyzed regiodivergent electrochemical CDC reaction of Schiff bases and commercially available hydroquinones to obtain three classes of chiral quaternary amino acid derivatives for the efficient assembly of complex scaffolds with excellent stereocontrol. The electrochemical anodic oxidation process with slow releasing of quinones serves as an internal syringe pump and provides high levels of reaction efficiency and enantiomeric control. The utility of this strategy is highlighted through the synthetic utility in the asymmetric total synthesis of (-)-fumimycin.

Toward a mechanistic understanding of Rhenium(VII) adsorption behavior onto aminated polymeric adsorbents: Batch experiments, spectroscopic analyses, and theoretical computations

Rhenium, a rare and critical metal, existing in the industrial wastewater has been aroused extensive interests recently, due to its environmental and resource issues. Chitosan, an easily available, low-cost and eco-friendly biopolymer, was prepared and modified by grafting primary, secondary, tertiary and quaternary amino groups, respectively. Adsorption behaviors and interactions between ReO4− and these four types of aminated adsorbents were investigated through batch experiments, spectroscopic analysis, and theoretical computations. Chitosan modified with secondary amines showed an extremely high uptake of ReO4− with 742.0 mg g−1, which was higher than any reported adsorbents so far. Furthermore, a relatively high adsorption selectivity for Re(VII), as well as the stable and facile regeneration of these aminated adsorbents revealed a promising approach for Re(VII) recovery in full-scale applications. The electrostatic attraction was illustrated to be the main adsorption mechanism by Fourier Transform Infrared Spectroscopy and X-ray Photoelectron Spectroscopy analyses. Significantly, the sub-steps of the adsorption process, encompassing the transformation of binding sites and the subsequent binding between these sites and the adsorbate, have been thoroughly investigated through the density functional theory (DFT) calculation method. This approach was firstly proposed to clearly demonstrate the differences in Re(VII) adsorption behavior onto four types of aminated adsorbents, resulting the importance of not only strong binding energy but also an appropriate binding spatial environmental for effective Re(VII) adsorption.

Stereoselective Biocatalytic α-Deuteration of L-Amino Acids by a Pyridoxal 5'-Phosphate-Dependent Mannich Cyclase.

α-Deuterated amino acids are valuable building blocks for developing deuterated drugs, and are important tools for studying biological systems. Biocatalytic deuteration represents an attractive strategy to directly access enantiopure α-deuterated amino acids. Here, we show that a PLP-dependent Mannich cyclase, LolT, involved in the biosynthesis of loline alkaloids, is capable of deuterating a diverse range of L-amino acids, including basic and acidic, nonpolar and polar, aliphatic and aromatic amino acids. Furthermore, complete deuteration of many amino acids can be achieved within minutes with exquisite control on the site- and stereoselectivity. During the course of this investigation, we also unexpectedly discovered that LolT exhibits β-elimination activity with L-cystine and O-acetyl-L-serine, confirming our previous hypothesis based on structural and phylogenetic analysis that LolT, a Cα-C bond forming enzyme, is evolved from a primordial Cβ-S lyase family. Overall, our study demonstrates that LolT is an extremely versatile biocatalyst, and can be used for not only heterocyclic quaternary amino acid biosynthesis, but also biocatalytic amino acid deuteration.

β-Turn Induction by a Diastereopure Azepane-Derived Quaternary Amino Acid.

β-Turns are one of the most common secondary structures found in proteins. In the interest of developing novel β-turn inducers, a diastereopure azepane-derived quaternary amino acid has been incorporated into a library of simplified tetrapeptide models in order to assess the effect of the azepane position and peptide sequence on the stabilization of β-turns. The conformational analysis of these peptides by molecular modeling, NMR spectroscopy, and X-ray crystallography showed that this azepane amino acid is an effective β-turn inducer when incorporated at the i + 1 position. Moreover, the analysis of the supramolecular self-assembly of one of the β-turn-containing peptide models in the solid state reveals that it forms a supramolecular helical arrangement while maintaining the β-turn structure. The results here presented provide the basis for the use of this azepane quaternary amino acid as a strong β-turn inducer in the search for novel peptide-based bioactive molecules, catalysts, and biomaterials.

Side effects based network construction and drug repositioning of ropinirole as a potential molecule for Alzheimer’s disease: an in-silico, in-vitro, and in-vivo study

Alzheimer’s disease (AD) is the leading cause of dementia in older adults. Drug repositioning is a process of finding new therapeutic applications for existing drugs. One of the methods in drug repositioning is to use the side-effect profile of a drug to identify a new therapeutic indication. The drugs with similar side-effects may act on similar biological targets and could affect the same biochemical process. In this study, we explored the Food and Drug Administration-approved drugs using PROMISCUOUS database to find those that have adverse effects profile comparable with the ligands being studied or used to treat AD. Here, we found that the ropinirole, a dopamine receptor agonist, shared a maximum number of side-effects with the drugs proven beneficial for treating AD. Furthermore, molecular modelling demonstrated that ropinirole exhibited strong binding affinity (−9.313 kcal/mol) and best ligand efficiency (0.49) with sigma-1 receptor. Here, we observed that the quaternary amino group of ropinirole is essential for binding with sigma-1 receptor. Molecular dynamic simulation indicated that the movement of the carboxy-terminal helices (α4/α5) could play a major role in the receptor’s physiological functions. The neurotoxicity induced by Aβ25–35 in SH-SY5Y cells was reduced by ropinirole at concentrations 10, 30, and 50 µM. The effect on spatial learning and memory was examined in mice with Aβ25–35 induced memory deficit using the radial arm maze. Ropinirole (10 and 20 mg/kg) significantly improved the short and long-term memories in the radial arm maze test. Our results suggest that ropinirole has the potential to be repositioned for AD treatment. Communicated by Ramaswamy H. Sarma

Molformer: Motif-Based Transformer on 3D Heterogeneous Molecular Graphs

Procuring expressive molecular representations underpins AI-driven molecule design and scientific discovery. The research mainly focuses on atom-level homogeneous molecular graphs, ignoring the rich information in subgraphs or motifs. However, it has been widely accepted that substructures play a dominant role in identifying and determining molecular properties. To address such issues, we formulate heterogeneous molecular graphs (HMGs) and introduce a novel architecture to exploit both molecular motifs and 3D geometry. Precisely, we extract functional groups as motifs for small molecules and employ reinforcement learning to adaptively select quaternary amino acids as motif candidates for proteins. Then HMGs are constructed with both atom-level and motif-level nodes. To better accommodate those HMGs, we introduce a variant of the Transformer named Molformer, which adopts a heterogeneous self-attention layer to distinguish the interactions between multi-level nodes. Besides, it is also coupled with a multi-scale mechanism to capture fine-grained local patterns with increasing contextual scales. An attentive farthest point sampling algorithm is also proposed to obtain the molecular representations. We validate Molformer across a broad range of domains, including quantum chemistry, physiology, and biophysics. Extensive experiments show that Molformer outperforms or achieves the comparable performance of several state-of-the-art baselines. Our work provides a promising way to utilize informative motifs from the perspective of multi-level graph construction. The code is available at https://github.com/smiles724/Molformer.

Highly Stereoselective Synthesis of γ,δ‐Unsaturated Quaternary α‐Amino Esters via the Tandem N‐Alkylation/Claisen Rearrangement of α‐Imino Allylesters

Abstractγ,δ‐Unsaturated amino acids are the backbone of various natural products and pharmaceuticals, while quaternary α‐amino acids are also powerful enzyme inhibitors, and both are very important compounds in bioorganic chemistry. A highly efficient synthesis of γ,δ‐unsaturated quaternary amino esters utilizing the tandem umpolung/Claisen rearrangement for α‐iminoallyl esters was developed. This method has a wide range of substrates taking account of the Hammett rule, and highly stereoselective Claisen rearrangement were achieved by the effect of DMSO or the ortho‐substituents of imino carbon. Furthermore, product functionalization also showed the usefulness of this reaction and the detailed reaction mechanism was elucidated from isotopic labeling experiments, kinetic isotope effects and crossover‐experiments.

Evaluation on the inclusion behavior of β-cyclodextrins with lycorine and its hydrochloride

Lycorine (Lyc) and its hydrochloride (Lyc∙HCl) as effective drugs can fight against many diseases including novel coronavirus (COVID-19) based on their antiviral and antitumor mechanism. Beta-cyclodextrin (β-CD) is considered a promising carrier in improving its efficacy while minimizing cytotoxicity due to the good spatial compatibility with Lyc. However, the detailed mechanism of inclusion interaction still remains to be further evaluated. In this paper, six inclusion complexes based on β-CDs, Lyc and Lyc∙HCl were processed through ultrasound in the mixed solvent of ethanol and water, and their inclusion behavior was characterized after lyophilization. It was found that the inclusion complexes based on sulfobutyl-beta-cyclodextrin (SBE-β-CD) and Lyc∙HCl had the best encapsulation effect among prepared inclusion complexes, which may be attributed to the electrostatic interaction between sulfonic group of SBE-β-CD and quaternary amino group of Lyc∙HCl. Moreover, the complexes based on SBE-β-CD displayed pH-sensitive drug release property, good solubilization, stability and blood compatibility, indicating their potential as suitable drug carriers for Lyc and Lyc∙HCl.

Laboratory Scale Continuous Flow Systems for the Enantioselective Phase Transfer Catalytic Synthesis of Quaternary Amino Acids.

The use of stereoselective phase-transfer catalysis as a reliable method for the enantioselective synthesis of optically active α-amino acid derivatives using achiral Schiff base esters has been well-developed in batch in the last 40 years. Recently, continuous flow technology has become of great interest in the academy and industry, since it offers safer process operating conditions and higher efficiency compared to a traditional batch processing. Herein, we wish to report the first example of enantioselective phase transfer benzylation of alanine Schiff base ester, under continuous flow conditions. Two different methodologies were investigated: a liquid-solid phase transfer catalytic benzylation using a packed-bed reactor and a liquid-liquid phase transfer catalytic benzylation in continuous stirred-tank reactors. Liquid-liquid phase transfer process in flow showed slightly better productivity than the batch process, while solid-liquid phase transfer benzylation proved much more advantageous in terms of productivity and space-time yield. Furthermore, continuous flow system allowed the isolation of benzylated product without any work up, with a significant simplification of the process. In both cases, phase transfer asymmetric benzylation promoted by Maruoka catalyst demonstrated high enantioselectivity of target quaternary amino ester in flow, up to 93% ee.

Synthesis of cationic β-cyclodextrin functionalized silver nanoparticles and their drug-loading applications.

Silver nanoparticles have attracted great attention owing to their distinct physicochemical properties, which inspire the development of their synthesis methodology and their potential biomedical applications. In this study, a novel cationic β-cyclodextrin (C-β-CD) containing a quaternary ammonium group and amino group was applied as a reducing agent as well as a stabilizing agent to prepare C-β-CD modified silver nanoparticles (CβCD-AgNPs). Besides, based on the inclusion complexation between drug molecules and C-β-CD, the application of CβCD-AgNPs in drug loading was explored by the inclusion interaction with thymol. The formation of AgNPs was confirmed by ultraviolet-visible spectroscopy (UV-vis) and X-ray diffraction spectroscopy (XRD). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed the prepared CβCD-AgNPs were well dispersed with particle sizes between 3-13 nm, and the zeta potential measurement result suggested that the C-β-CD played a role in preventing their aggregation in solution. 1H Nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR) revealed the encapsulation and reduction of AgNPs by C-β-CD. The drug-loading action of CβCD-AgNPs was demonstrated by UV-vis and headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS), and the results of TEM images showed the size increase of nanoparticles after drug loading.

MODIFICATION OF MONTMORILLONITE FOR OBTAINING NANOCOMPOSITES BASED ON POLAR POLYMERS

This review covers almost all known categories of compounds used to modify montmorillonite to obtain nanocomposites based on polar polymers. Organic modifiers such as quaternary ammonium ions, quaternary phosphonium ions, amino acids and other organic compounds are commonly used to modify montmorillonite (MMT). The main directions of scientific research in this field are considered, namely the modification of MMT with ammonium surfactants, phosphonium surfactants, amino acids and nonionic surfactants. The review used 67 sources related to peer-reviewed publications, mostly from the last 10-15 years. The largest number of publications devoted to the modification of MMT was published in the period from 2004 to 2016. Nanocomposites based on epoxy resins are especially widely presented in the literature. Epoxy-based materials have been used for many years as convenient matrices for dispersing MMT due to the advantages of properties of the obtained polymer nanocomposites, such as mechanical strength, non-flammability and thermal stability. The methods of surface modification of MMT with organic modifiers considered in the article are a powerful tool for the production of polymer nanocomposite materials based on polar polymers. Amine modification of MMT allowed the formation of highly effective materials, in particular epoxy/MMT materials. These nanocomposites have demonstrated extraordinary material properties compared to virgin polymers and can therefore be used as an alternative to conventional materials such as steel and wood, reducing the cost and weight of products. Nanocomposites based on polar polymers occupy an important place among all polymer nanocomposites as modern materials used in the aerospace, automotive and electrical industries.

Efficient Anion-Exchange Membranes with Anti-Scaling Properties Obtained by Surface Modification of Commercial Membranes Using a Polyquaternium-22.

Anion-exchange membranes modified with a polyquaternium-22 (PQ-22) polymer were studied for their use in electrodialysis. The use of PQ-22 for modification makes it possible to "replace" weakly basic amino groups on the membrane surface with quaternary amino groups. It was found that the content of quaternary amino groups in PQ-22 is higher than the content of carboxyl groups, which is the reason for the effectiveness of this polymer even when modifying Ralex AHM-PES membranes that initially contain only quaternary amino groups. In the case of membranes containing weakly basic amino groups, the PQ-22 polymer modification efficiency is even higher. The surface charge of the modified MA-41P membrane increased, while the limiting current density on the current-voltage curves increased by more than 1.5 times and the plateau length decreased by 2.5 times. These and other characteristics indicate that the rate of water splitting decreased and the electroconvective mixing at the membrane surface intensified, which was confirmed by direct visualization of vortex structures. Increasing the surface charge of the commercial MA-41P anion-exchange membrane, reducing the rate of water splitting, and enhancing electroconvection leads to mitigated scaling on its surface during electrodialysis.

Design of Photoredox-Catalyzed Giese-Type Reaction for the Synthesis of Chiral Quaternary α-Aryl Amino Acid Derivatives via Clayden Rearrangement.

Chiral quaternary α-aryl amino acids are biologically valued but synthetically challenging building blocks. Herein, we report a strategy for the synthesis of molecular architectures by unifying a photoredox catalytic asymmetric Giese-type reaction and Clayden rearrangement. A new class of chiral Karady-Beckwith dehydroalanines is designed and serves as a versatile handle for the photoredox-mediated highly stereoselective Giese-type reaction with feedstock carboxylic acids and tertiary amines. Subsequent Clayden rearrangement delivers chiral quaternary α-aryl amino acid derivatives with high stereoselectivity. The versatile approach offers a reliable source for the assembly of highly demanding chiral building blocks.

Synthesis and Characterization of Starch-Based Acid- and Alkali-Resistant Hydrogels Optimized by Box-Behnken Response Surface Methodology.

Applying gel-type solid chlorine dioxide for the sustained release of chlorine dioxide has several shortcomings, such as no resistance to acid and alkali corrosion and poor mechanical properties. However, introducing quaternary ammonium, carboxyl, and amino groups into the hydrogel system can enhance its acid and alkali resistance. In this study, the effects of concentration of dry heat-modified starch, quaternized carboxymethyl cellulose, and chitin on the swelling behavior and mechanical properties of starch-based acid- and alkali-resistant hydrogels are investigated. The feasibility of the actual and predicted values of the tentative results is verified based on the response surface design to determine the optimal concentration ratio of acid- and alkali-resistant hydrogels. The results reveal that optimized process parameters are reliable. The maximum swelling ratio and compressive stress of the hydrogel are 5358.00% and 44.45 kPa, respectively, and its swelling behavior conforms to the pseudo second-order kinetic model. Thus, the present study can provide a new method of developing efficient starch-based chlorine dioxide hydrogels for the sustained release of chlorine dioxide.

Separation of Phycobiliprotein from Nostoc Commune by Using Ion-Exchange Membrane with Quaternary Amine

ABSTRACT Phycobiliprotein (PB), which is produced by cyanobacteria, has potential applications as a valuable pharmaceutical product. In this study, PB was separated by using a nonwoven-fabric membrane (Rx-1) that contained quaternary amino groups. PB was extracted from a Nostoc commune, which is a type of microalga, by disrupting the cell walls by a freeze–thaw method. Two types of biomolecules, namely PB and other biomolecules X, were identified by gel permeation chromatography. Permeation of the PB-containing solution through Rx-1 increased the purity of the PB in the filtrate from 0.25 to 0.45. The adsorption constant (K p) and maximum adsorbed amount of each protein on Rx-1 (q max) were determined by fitting the experimental data to a mathematical model. The obtained values for K p and q max were used to simulate scaled-up treatment of a PB-containing solution. Permeation of a PB-containing solution (3.0 L at 1.2 × 10−3 m3/h) through Rx-1 (volume of scale-up membrane, 8.0 × 10−4 m3) enabled PB separation for 26 h. Further PB purification could be achieved by using the Rx-1 membrane in combination with precipitation with ammonium sulfate solution and an ultrafiltration membrane.