Effects of Baicalein and Chrysin on the Structure and Functional Properties of β-Lactoglobulin

Two flavonoids with similar structures, baicalein (Bai) and chrysin (Chr), were selected to investigate the interactions with β-lactoglobulin (BLG) and the influences on the structure and functional properties of BLG by multispectral methods combined with molecular docking and dynamic (MD) simulation techniques. The results of fluorescence quenching suggested that both Bai and Chr interacted with BLG to form complexes with the binding constant of the magnitude of 105 L·mol−1. The binding affinity between BLG and Bai was stronger than that of Chr due to more hydrogen bond formation in Bai–BLG binding. The existence of Bai or Chr induced a looser conformation of BLG, but Chr had a greater effect on the secondary structure of BLG. The surface hydrophobicity and free sulfhydryl group content of BLG lessened due to the presence of the two flavonoids. Molecular docking was performed at the binding site of Bai or Chr located in the surface of BLG, and hydrophobic interaction and hydrogen bond actuated the formation of the Bai/Chr–BLG complex. Molecular dynamics simulation verified that the combination of Chr and BLG decreased the stability of BLG, while Bai had little effect on it. Moreover, the foaming properties of BLG got better in the presence of the two flavonoids compounds and Bai improved its emulsification stability of the protein, but Chr had the opposite effect. This work provides a new idea for the development of novel dietary supplements using functional proteins as flavonoid delivery vectors.

Theoretical Researches On Binding Modes and Stability of Hydrogen Bonds Between Uracil and Formic Acid

The hydrogen bond formation with formic acid would affect the complementary pair of bases between uracil and adenine, but the binding modes and spectral properties of hydrogen bonds are still obscure. Density functional theory and time-dependent density functional theory were applied to investigate the intermolecular hydrogen bonds between uracil and formic acid. The reduced density gradient (RDG), bond lengths and vibration absorption frequencies revealed that the most probable uracil-formic acid (U-FA) interaction mode formed in the position c of FA and the site 1 of U, that is, the mode 1c. The theoretical parameters in excited state complexes manifested that the variety of hydrogen bond configurations led to different degrees of strengthening or weakening of molecular interaction. In the implicit solvent (water), the formations of O-H∙∙∙O in the uracil-formic acid complexes were promoted obviously. These theoretical studies would positively affect the researches of life science and medicinal chemistry.

Molecular Modeling Insights into Upadacitinib Selectivity upon Binding to JAK Protein Family

Rheumatoid arthritis (RA) is a chronic disease characterized by bone joint damage and incapacitation. The mechanism underlying RA pathogenesis is autoimmunity in the connective tissue. Cytokines play an important role in the human immune system for signal transduction and in the development of inflammatory responses. Janus kinases (JAK) participate in the JAK/STAT pathway, which mediates cytokine effects, in particular interleukin 6 and IFNγ. The discovery of small molecule inhibitors of the JAK protein family has led to a revolution in RA therapy. The novel JAK inhibitor upadacitinib (RinvoqTM) has a higher selectivity for JAK1 compared to JAK2 and JAK3 in vivo. Currently, details on the molecular recognition of JAK1 by upadacitinib are not available. We found that characteristics of hydrogen bond formation with the glycine loop and hinge in JAKs define the selectivity. Our molecular modeling study could provide insight into the drug action mechanism and pharmacophore model differences in JAK isoforms.

Exploration of the Photocatalytic Cycle for Sacrificial Hydrogen Evolution by Conjugated Polymers Containing Heteroatoms

We analyze the photocatalytic activity of heteroatom containing linear conjugated polymers for sacrificial hydrogen evolution using a recently proposed photocatalytic cycle. We find that the thermodynamic barrier to electron transfer, relevant both in the presence and absence of noble metal co-catalysts, changes with polymer composition, reducing upon going from electron-rich to electron-poor polymers, and disappearing completely for the most electron-poor polymers in a water rich environment. We discuss how the latter is probably the reason why electron-poor polymers are generally more active for sacrificial hydrogen evolution than their electron-rich counterparts. We also study the barrier to hydrogen-hydrogen bond formation on the polymer rather than the co-catalyst and find that it too changes with composition but is always, at least for the polymer studied here, much larger than that experimentally reported for platinum. Therefore, it is expected that in the presence of any noble metal particles these will act as the site of hydrogen evolution.

Nonenzymatic Deamidation Mechanism on a Glutamine Residue with a C-Terminal Adjacent Glycine Residue: A Computational Mechanistic Study

The deamidation of glutamine (Gln) residues, which occurs non-enzymatically under physiological conditions, triggers protein denaturation and aggregation. Gln residues are deamidated via the cyclic glutarimide intermediates to l-α-, d-α-, l-β-, and d-β-glutamate residues. The production of these biologically uncommon amino acid residues is implicated in the pathogenesis of autoimmune diseases. The reaction rate of Gln deamidation is influenced by the C-terminal adjacent (N +1) residue and is highest in the Gln-glycine (Gly) sequence. Here, we investigated the effect of the (N + 1) Gly on the mechanism of Gln deamidation and the activation barrier using quantum chemical calculations. Energy-minima and transition-state geometries were optimized by the B3LYP density functional theory, and MP2 calculations were used to obtain the single-point energy. The calculated activation barrier (85.4 kJ mol−1) was sufficiently low for the reactions occurring under physiological conditions. Furthermore, the hydrogen bond formation between the catalytic ion and the main chain of Gly on the C-terminal side was suggested to accelerate Gln deamidation by stabilizing the transition state.

Synthesis and properties of vinyl benzyl alcohol copolymers with styrene

Objectives. Synthesis and study of the properties of copolymers of vinyl benzyl alcohol (VBA) with styrene with antimicrobial properties.Methods. The study employed infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy, thin-layer chromatography, viscometry, and elemental analysis. The sessile drop method and the pencil method were respectively utilized to determine the contact angles and hardness of the films. The process of testing the film coatings’ resistance to the effects of molds consisted of contaminating the film coatings applied to the glass with mold spores of the All-Russian Collection of Microorganisms in a solution of mineral salts without sugar (Czapek–Dox medium).Results. Homopolymers of vinyl benzyl acetate and its copolymers with styrene were synthesized in this study. Homo- and copolymers of VBA were obtained by saponification. IR and proton NMR (1H NMR) spectroscopy determined the composition of the copolymers. Employing IR spectroscopy, the degree of saponification was monitored by the appearance of the hydroxyl group absorption band and the disappearance of the ester group absorption band. According to the IR spectroscopy data, only an insignificant (~3%) amount of ester groups remains in the saponified copolymers. The influence of the copolymers’ composition on their solubility in various solvents is demonstrated. IR spectroscopy of the copolymers revealed hydrogen-bond formation between the unreacted ester groups and hydroxyl groups formed due to the saponification. The viscometry of the solutions of mixtures of saponified and unsaponified copolymers, solutions of mixtures of saponified copolymer with polyvinyl acetate, and viscometry of saponified copolymers in various solvents all support this conclusion. These bonds’ concentration depends on the copolymer’s composition and can be controlled by the nature of the solvent from which these copolymers’ films are formed. Saponified copolymer solutions form smooth, transparent film coatings with excellent adhesion to metals and silicate glass surfaces. The contact angle of these films, like the hardness, decreases as the VBA units’ concentration in the copolymers increases and depends on the solvent polarity used to form the films. It has been demonstrated that increasing the VBA units concentration suppresses the microorganisms’ growth.Conclusions. Film coatings made of copolymers of styrene with VBA have been shown to have high biocidal activity against molds; can be used to protect structural materials and products from the effects of microorganisms.

Porphyrin Molecules Decorated on Metal–Organic Frameworks for Multi-Functional Biomedical Applications

Metal–organic frameworks (MOFs) have been widely used as porous nanomaterials for different applications ranging from industrial to biomedicals. An unpredictable one-pot method is introduced to synthesize NH2-MIL-53 assisted by high-gravity in a greener media for the first time. Then, porphyrins were deployed to adorn the surface of MOF to increase the sensitivity of the prepared nanocomposite to the genetic materials and in-situ cellular protein structures. The hydrogen bond formation between genetic domains and the porphyrin’ nitrogen as well as the surface hydroxyl groups is equally probable and could be considered a milestone in chemical physics and physical chemistry for biomedical applications. In this context, the role of incorporating different forms of porphyrins, their relationship with the final surface morphology, and their drug/gene loading efficiency were investigated to provide a predictable pattern in regard to the previous works. The conceptual phenomenon was optimized to increase the interactions between the biomolecules and the substrate by reaching the limit of detection to 10 pM for the Anti-cas9 protein, 20 pM for the single-stranded DNA (ssDNA), below 10 pM for the single guide RNA (sgRNA) and also around 10 nM for recombinant SARS-CoV-2 spike antigen. Also, the MTT assay showed acceptable relative cell viability of more than 85% in most cases, even by increasing the dose of the prepared nanostructures.

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

Nitrogen-containing scaffolds are ubiquitous in nature and constitute an important class of building blocks in organic synthesis. The asymmetric aza-Michael reaction (aza-MR) alone or in tandem with other organic reaction(s) is an important synthetic tool to form new C–N bond(s) leading to developing new libraries of diverse types of bioactive nitrogen compounds. The synthesis and application of a variety of organocatalysts for accomplishing highly useful organic syntheses without causing environmental pollution in compliance with ‘Green Chemistry” has been a landmark development in the recent past. Application of many of these organocatalysts has been extended to asymmetric aza-MR during the last two decades. The present article overviews the literature published during the last 10 years concerning the asymmetric aza-MR of amines and amides catalysed by organocatalysts. Both types of the organocatalysts, i.e., those acting through non-covalent interactions and those working through covalent bond formation have been applied for the asymmetric aza-MR. Thus, the review includes the examples wherein cinchona alkaloids, squaramides, chiral amines, phase-transfer catalysts and chiral bifunctional thioureas have been used, which activate the substrates through hydrogen bond formation. Most of these reactions are accompanied by high yields and enantiomeric excesses. On the other hand, N-heterocyclic carbenes and chiral pyrrolidine derivatives acting through covalent bond formation such as the iminium ions with the substrates have also been included. Wherever possible, a comparison has been made between the efficacies of various organocatalysts in asymmetric aza-MR.

Self-Healing Hydrogels Based on Sodium Carboxymethyl Cellulose/Poly(vinyl alcohol) Reinforced with Montmorillonite

Currently, self-healing hydrogels prepared from the green process have been studied for various applications, especially in the biomedical field. This work fabricated the self-healing hydrogel based on sodium carboxymethyl cellulose/poly(vinyl alcohol)/montmorillonite by acidifying the mixture with citric acid. SEM measurements showed well-dispersed montmorillonite in the hydrogels. Cytotoxicity values >100% were seen with montmorillonite added, which indicated cell growth and no cell toxicity. Montmorillonite addition not only reinforced the networks but also improved self-healing ability. The tensile strength of the original uncut hydrogel with montmorillonite (P1C8M1) was 61 kPa, whereas the healed hydrogel showed 57 kPa. The hydrogel healed completely within 10 days, without any cracks, i.e., a 93% healing efficiency, or higher than the ~60% of the non-reinforced hydrogel. This confirmed strong hydrogen bond formation between the polymer and montmorillonite. The self-healing ability of this non-toxic hydrogel, reinforced with montmorillonite, makes it valuable for use in biomedical fields.