Metal–Organic Framework as a Fluorescent and Colorimetric Dual-Signal Readout Biosensor Platform for the Detection of a Genetic Sequence from the SARS-CoV‑2 Genome

The quest for the development of high-accuracy, point-of-care, and cost-effective testing platforms for SARS-CoV-2 infections is ongoing as current diagnostics rely on either assays based on costly yet accurate nucleic acid amplification tests (NAAT) or less selective and less sensitive but rapid and cost-effective antigen tests. As a potential solution, this work presents a fluorescence-based detection platform using a metal–organic framework (MOF) in an effective assay, demonstrating the potential of MOFs to recognize specific targets of the SARS-CoV-2 genome with high accuracy and rapid process turnaround time. As a highlight of this work, positive detection of SARS-CoV-2 is indicated by a visible color change of the MOF probe with ultrahigh detection selectivities down to single-base mismatch nucleotide sequences, thereby providing an alternative avenue for the development of innovative detection methods for diverse viral genomes

Pharmacophore-Based 3D-QSAR Analysis of Thienyl Chalcones as a New Class of Human MAO‑B Inhibitors: Investigation of Combined Quantum Chemical and Molecular Dynamics Approach

Selective monoamine oxidase-B (MAO-B) inhibitors are imperative in the treatment of various neurodegenerative disorders. Herein, we describe the pharmacophore generation and atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR) analyses of previously reported thiophene-based hMAO-B inhibitors by our research group. The aim of this study was to identify the principal structural features that could potentially be responsible for the inhibitory activity of hMAO-B inhibitors. The best pharmacophore model generated was the four-point assay of AHRR.8. The pharmacophore model exhibited good correlation with its predictability of the statistically valid 3D-QSAR analyses. Density functional theory calculations were further employed on the lead molecule (2E)-1-(5-bromothiophen-2-yl)-3-[4-(dimethylamino) phenyl] prop-2-en-1-one (Tb5) to investigate the electrostatic potential surface and analyze the natural bond orbital toward the binding characteristics. Molecular dynamics simulations were performed to characterize the molecular level interactions and relative energies of the hMAO isoforms: hMAO-A and hMAO-B with three potent and selective hMAO-B inhibitors (Tb5, Tb6, and Tb9). The results of both continuous and accelerated molecular dynamics simulations demonstrate a distinct preference of the three ligands to bind to hMAO-B rather than hMAO-A

Force-Induced Near-Infrared Chromism of Mechanophore-Linked Polymers

A near-infrared (NIR) mechanophore was developed and incorporated into a poly­(methyl acrylate) chain to showcase the first force-induced NIR chromism in polymeric materials. This mechanophore, based on benzo­[1,3]­oxazine (OX) fused with a heptamethine cyanine moiety, exhibited NIR mechanochromism in solution, thin-film, and bulk states. The mechanochemical activity was validated using UV–vis–NIR absorption/fluorescence spectroscopies, gel permeation chromatography (GPC), NMR, and DFT simulations. Our work demonstrates that NIR mechanochromic polymers have considerable potential in mechanical force sensing, damage detection, bioimaging, and biomechanics

Studies on the interaction between HSA and new halogenated metformin derivatives: influence of lipophilic groups in the binding ability

In the type II diabetes mellitus, Metformin hydrochloride is recommended as a common FAD approved drug. Synthesis of novel metformin series has been widely explored, mainly due to its biological importance and to improve their pharmacokinetic profile. Generally, human serum albumin (HSA) is the main protein used to study drug viability in vitro analysis. Thus, the present study reports the synthesis of three new halogenated metformin derivatives (MFCl, MFBr and MFCF3) and its interaction toward HSA by multiple spectroscopic techniques (UV-Vis, circular dichroism, steady-state, time-resolved and synchronous fluorescence), combined to computational methods (molecular docking and quantum chemical calculation). The interaction between each halogenated metformin derivative and HSA is spontaneous (ΔG°ΔS°>0), moderate (Ka and Kb ≈ 104 M−1) and occurs preferentially in the subdomain IIA (close to Trp-214 residue). Molecular docking results suggested hydrogen bonding, van der Waals and hydrophobic interactions as the main binding forces. Quantum chemical calculations suggested imino groups as the most intense electrostatic negative potentials, while the positive electrostatic potential is located at the hydrogen atoms on N,N-dimethyl and the phenyl systems which can help the hydrophobic interactions. Communicated by Ramaswamy H. Sarma</p