Novel aryl (dithioglycosyl)methane derivatives as anti-proliferative agents.

In a quest of developing carbohydrate derived anti-cancer agents, novel carbohydrate dithioacetal derivatives have been synthesized and evaluated for their potential as anti-proliferative agents against breast cancer cell lines (MCF-7 and MDA-MB-231) as well as non-cancerous kidney epithelial cell line (NKE). Total 18 compounds have been screened and 3 compounds showed promising anti-proliferative activities against cancer cells with low cytotoxicity to the normal cells using MTT assay. The mode of action of the best active compound has been proposed based on several microscopic studies.

Isomer-Specific, Cryogenic Ion Vibrational Spectroscopy Investigation of D- and N-Tagged, Protonated Formic Acid Complexes Using Two-Color, IR-IR Photobleaching.

Here we analyze cryogenic ion vibrational spectra of tagged protonated formic acid (PFA) with electronic structure and anharmonic vibrational calculations to establish the isomers generated by electrospray ionization (ESI) followed by buffer gas cooling to ∼25 K. Two isomers are identified (the form (E,Z) and the form (E,E)) and generated in comparable abundance despite the fact that the calculated E,E structure lies 6.40 kJ mol above the E,Z form.

Demonstration of Capture, Cooling, Tagging, and Spectroscopic Characterization of UV Photoproduct Ions in a Cryogenic Ion Trap: Application to 266 nm Photofragment Ions from Rhodamine 6G.

We demonstrate a method to determine the structures of the primary photodissociation products from a cryogenically cooled parent ion. In this approach, a target ion is cooled by a pulse of buffer gas and tagged in a 20 K Paul trap. The cold ion is then photodissociated by pulsed (∼5 ns) UV laser excitation, and the ionic products are trapped, cooled, and tagged by introduction of a second buffer gas pulse in the same trap.

Convergent synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-polysaccharide of Salmonella milwaukee (group U) O:43 strain.

Synthesis of the pentasaccharide repeating unit of the cell O-polysaccharide produced by Salmonella milwaukee O:43 strain (group U) has been achieved in very good yield adopting a convergent stereoselective [3 + 2] block glycosylation strategy. Thioglycosides and glycosyl trichloroacetimidate derivative were used as glycosyl donors in the presence of a combination of N-iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) as thiophilic activator and TMSOTf as trichloroacetimidate activator respectively. The stereochemical outcome of all glycosylation reactions was excellent.

Characterization of the Oxazolone and Macrocyclic Motifs in the b ( = 2-5) Product Ions from Collision-Induced Dissociation of Protonated Oligoglycine Peptides with Isomer-Selective, Cryogenic Vibrational Spectroscopy.

Collision-induced dissociation (CID) of small, protonated peptides leads to the formation of b-type fragment ions that can occur with several structural motifs driven by different covalent intramolecular bonding arrangements. Here, we characterize the so-called "oxazolone" and "macrocycle" ion structures that occur upon CID of oligoglycine peptides (G) ions ( = 2-6). This is determined by acquiring the vibrational band patterns of the cryogenically cooled, D-tagged ions obtained using isomer-selective, two-color IR-IR photobleaching and analyzing them with predicted (DFT) harmonic spectra for the candidate structures.

Individualized Homeopathic Medicines in the Treatment of Post-COVID-19 Fatigue in Adults: Single-Blind, Randomized, Placebo-Controlled Trial.

Introduction: The coronavirus disease 2019 (COVID-19) is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 fatigue is one of those challenges, becoming increasingly common as the pandemic evolves, as it impairs the quality of life of an individual. This trial attempts to identify the preliminary evidence of the efficacy of individualized homeopathic medicines (IHMs) against placebos in the treatment of post-COVID-19 fatigue in adults.

Straightforward synthesis of the hexasaccharide repeating unit of the O-specific polysaccharide of Salmonella arizonae O62.

A straightforward synthesis of the hexasaccharide repeating unit of the O-specific polysaccharide of Salmonella arizonae O62 was achieved in very good yield applying sequential glycosylation strategy. Successful regioselective glycosylation of the di-hydroxylated L-rhamnose moiety allowed achieving the desired compound in minimum number of synthetic steps. TEMPO catalyzed and [bis(acetoxy)iodo]benzene (BAIB) mediated late stage regioselective oxidation of a primary hydroxyl group into carboxylic acid was achieved in the hexasaccharide derivative.

Observation of Slow Eigen-Zundel Interconversion in H(HO) Clusters upon Isomer-Selective Vibrational Excitation and Buffer Gas Cooling in a Cryogenic Ion Trap.

The formation of isomers when trapping floppy cluster ions in a temperature-controlled ion trap is a generally observed phenomenon. This involves collisional quenching of the ions initially formed at high temperature by buffer gas cooling until their internal energies fall below the barriers in the potential energy surface that separate them. Here we explore the kinetics at play in the case of the two isomers adopted by the H(HO) cluster ion that differ in the proton accommodation motif.

The Redox-Active Conopeptide Derived from the Venom Duct Transcriptome of Assists in the Oxidative Folding of Conotoxin.

The tetrapeptides Li504 and Li520, differing in the modification of the 4--hydroxylation of proline, are novel conopeptides derived from the venom duct transcriptome of the marine cone snail . These predicted mature peptides are homologous to the active site motif of oxidoreductases that catalyze the oxidation, reduction, and rearrangement of disulfide bonds in peptides and proteins. The estimated reduction potential of the disulfide of Li504 and Li520 is within the range of disulfide reduction potentials of oxidoreductases, indicating that they may catalyze the oxidative folding of conotoxins.

Unravelling the electronic nature of C-FO-C non-covalent interaction in proteins and small molecules in the solid state.

The participation of organic fluorine as a halogen bond donor is rare and is sensitive to the electronic environment in the vicinity of the fluorine atom. The enhancement in the electropositive character (the σ-hole formalism) in fluorine is established by the presence of electron withdrawing groups and this has been examined in the solid-state structures in small molecules and proteins. Short, directional FO contacts have been observed and physical insights obtained, from quantum mechanical calculations, via the molecular electrostatic potential, an analysis of their topological features from atoms-in-molecules, and donor-acceptor characteristics from natural bond orbital analyses.

In Silico Identification of Potential Natural Product Inhibitors of Human Proteases Key to SARS-CoV-2 Infection.

Presently, there are no approved drugs or vaccines to treat COVID-19, which has spread to over 200 countries and at the time of writing was responsible for over 650,000 deaths worldwide. Recent studies have shown that two human proteases, TMPRSS2 and cathepsin L, play a key role in host cell entry of SARS-CoV-2. Importantly, inhibitors of these proteases were shown to block SARS-CoV-2 infection.

The Prodigious Hydrogen Bonds with Sulfur and Selenium in Molecular Assemblies, Structural Biology, and Functional Materials.

Hydrogen bonds (H-bonds) play important roles in imparting functionality to the basic molecules of life by stabilizing their structures and directing their interactions. Numerous studies have been devoted to understanding H-bonds involving highly electronegative atoms like nitrogen, oxygen, and halogens and consequences of those H-bonds in chemical reactions, catalysis, and structure and function of biomolecules; but the involvement of less electronegative atoms like sulfur and selenium in H-bond formation establishes the concept of noncanonical H-bonds. Initially belittled for the "weak" nature of their interactions, these perceptions have gradually evolved over time through dedicated efforts by several research groups.

Non-conventional Hydrogen Bonding and Aromaticity: A Systematic Study on Model Nucleobases and Their Solvated Clusters.

The conceptual development of aromaticity is essential to rationalize and understand the structure and behavior of aromatic heterocycles. This work addresses for the first time, the interconnection between aromaticity and sulfur/selenium centered hydrogen bonds (S/SeCHBs) involved in representative heterocycle models of canonical nucleobases (2-Pyridone; 2PY) and its sulfur (2-Thiopyridone; 2TPY) and selenium (2-Selenopyridone; 2SePY) analogs. The nucleus-independent chemical shift (NICS) and gauge induced magnetic current density (GIMIC) values suggested significant reduction of aromaticity upon replacement of exocyclic carbonyl oxygen with sulfur and selenium.

Characterization of (Boc-Cys/Sec-NHMe) and (Boc-Cys/Sec-OMe) : Evidence of local conformational difference between disulfide and diselenide.

Conformations of disulfide and diselenide were compared in (Boc-Cys/Sec-NHMe) and (Boc-Cys/Sec-OMe) using X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, density functional theory (DFT), and circular dichroism (CD) spectroscopy. Conformations of disulfide/diselenide in polypeptides are defined based on the sign of side chain torsion angle χ (-CH -S/Se-S/Se-CH -); negative indicates left-handed and positive indicates right-handed orientation. In the crystals of (Boc-Cys-OMe) and (Boc-Sec-OMe) , the disulfide exhibits a left-handed and the diselenide a right-handed orientation.

Nature and Strength of M-H···S and M-H···Se (M = Mn, Fe, & Co) Hydrogen Bond.

The significance of dispersion contribution in the formation of strong hydrogen bonds (H-bonds) can no more be ignored. It was illustrated that less electronegative and electropositive H-bond acceptors such as S, Se, and Te are also capable of forming strong N-H···Y H-bonds, mostly due to the high polarizabilities of H-bond acceptor atoms. Herein, for the first time, we report the evidence of formation of nonconventional M-H···Y H-bonds between metal hydrides (M-H, M = Mn, Fe, Co) and chalcogen H-bond acceptors (Y = O, S, or Se).