24 research outputs found
An Insight into the Interaction Between α-Ketoamide-Based Inhibitor and Coronavirus Main Protease: A Detailed in Silico Study
The search for therapeutic drugs
that can neutralize the effects of COVID-2019 (SARS-CoV-2) infection is the
main focus of current research. The coronavirus main protease (Mpro)
is an attractive target for anti-coronavirus drug design. Further, α-ketoamide is proved to be very
effective as a reversible covalent-inhibitor against cysteine proteases.
Herein, we report on the non-covalent to the covalent adduct formation mechanism
of α‑ketoamide-based inhibitor with the enzyme active site amino acids by
QM/SQM model (QM= quantum mechanical, SQM= semi-empirical QM). To uncover the
mechanism, we focused on two
approaches: a concerted and
a stepwise fashion.
The concerted pathway proceeds via deprotonation
of the thiol of cysteine (here, Cys145 SgH)
and simultaneous reversible nucleophilic attack of sulfur onto the α-ketoamide
warhead. In this work, we propose three plausible
concerted pathways. On the contrary, in a traditional two-stage pathway, the
first step is proton transfer from Cys145 SgH to
His41 Nd
forming an ion pair, and consecutively, in the second step, the thiolate ion attacks
the a-keto
group to form a thiohemiketal. In this reaction, we find that the stability of
the tetrahedral intermediate oxyanion/hydroxyl hole plays an important role. Moreover,
as the α-keto group has two faces Si or Re for the nucleophilic
attack, we considered both possibilities of attack leading to S- and
R-thiohemiketal.
We computed the structural, electronic, and energetic parameters of all
stationary points including transition states via ONIOM methodology at B3LYP/6-31G(d):PM6 level. Furthermore,
to get more accurate results, we also calculated the single-point dispersion-corrected energy profile by
using ωB97X-D/6-31G(d,p):PM6 level. Additionally, to characterize covalent,
weak noncovalent interaction (NCI) and hydrogen-bonds, we applied NCI-reduced
density gradient (NCI-RDG) methods along with Bader’s Quantum Theory of
Atoms-in-Molecules (QTAIM) and natural bonding orbital (NBO) analysis.
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Substituent effect on fluorescence signaling of the cell permeable HSO4- receptors through single point to ratiometric response in green solvent
Two new 2-(2-aminophenyl)benzimidazole-based HSO4- ion selective receptors, 6-(4-nitrophenyl)-5,6-dihydrobenzo4,5]imidazo1,2-c]quinazoline (L1H) and 6-(4-methoxyphenyl)-5,6-dihydrobenzo4,5]imidazo1,2-c] quinazoline (L2H), and their 1 : 1 molecular complexes with HSO4- were prepared in a facile synthetic method and characterized by physicochemical and spectroscopic techniques along with the detailed structural analysis of L1H by single crystal X-ray crystallography. Both receptors (L1H and L2H) behave as highly selective chemosensor for HSO4- ions at biological pH in ethanol-water HEPES buffer (1/5) (v/v) medium over other anions such as F-, Cl-, Br-, I-, AcO-, H2PO4-, N-3(-) and ClO4-. Theoretical and experimental studies showed that the emission efficiency of the receptors (L1H and L2H) was tuned successfully through single point to ratiometric detection by employing the substituent effects. Using 3 sigma method the LOD for HSO4- ions were found to be 18.08 nM and 14.11 nM for L1H and L2H, respectively, within a very short responsive time (15-20 s) in 100 mM HEPES buffer (ethanol-water: 1/5, v/v). Comparison of the utility of the probes (L1H and L2H) as biomarkers for the detection of intracellular HSO4- ions concentrations under a fluorescence microscope has also been included and both probes showed no cytotoxic effect
Development of activated carbon using one step carbonization and activation reaction by polymer blend method
ABSTRACT. In the present work, a one step carbon activation process was developed by stabilized poly-blend. It is carbonized in nitrogen atmosphere and activated in steam in one step for known interval of times to enhance the surface area and develop interconnected porosity. The weight-loss behavior during steam activation of stabilized poly-blend at different temperatures, surface area and pore size distribution were studied to identify the optimum synthesis parameters. The results of surface characteristics were compared with those of activated carbon prepared by carbonization and activation in two steps. It was found that activation temperature has profound effect on surface characteristics. As activation temperature was raised from 800˚C to 1150˚C, surface area of activated carbon increased about three times. In addition to surface area, average pore diameter also increases with increasing activation temperature. Thus, activated carbon with high percentage of porosity and surface area can be developed by controlling the activation temperature during activation process
A napthelene-pyrazol conjugate: Al(III) ion-selective blue shifting chemosensor applicable as biomarker in aqueous solution
A newly synthesized and crystalographically characterized napthelene-pyrazol conjugate, 1-(5-phenyl-1H-pyrazole-3-ylimino)-methyl]-naphthalen-2-ol (HL) behaves as an Al(III) ion-selective chemosensor through internal charge transfer (ICT)-chelation-enhanced fluorescence (CHEF) processes in 100 mM HEPES buffer (water-DMSO 5 : 1, v/v) at biological pH with almost no interference of other competitive ions. This mechanism is readily studied from electronic, fluorimetric and H-1 NMR titration. The probe (HL) behaved as a highly selective fluorescent sensor for Al(III) ions as low as 31.78 nM within a very short response time (15-20 s). The sensor (HL), which has no cytotoxicity, is also efficient in detecting the distribution of Al(III) ions in HeLa cells via image development under fluorescence microscope
Sequence-Agnostic Multi-Object Navigation
The Multi-Object Navigation (MultiON) task requires a robot to localize an
instance (each) of multiple object classes. It is a fundamental task for an
assistive robot in a home or a factory. Existing methods for MultiON have
viewed this as a direct extension of Object Navigation (ON), the task of
localising an instance of one object class, and are pre-sequenced, i.e., the
sequence in which the object classes are to be explored is provided in advance.
This is a strong limitation in practical applications characterized by dynamic
changes. This paper describes a deep reinforcement learning framework for
sequence-agnostic MultiON based on an actor-critic architecture and a suitable
reward specification. Our framework leverages past experiences and seeks to
reward progress toward individual as well as multiple target object classes. We
use photo-realistic scenes from the Gibson benchmark dataset in the AI Habitat
3D simulation environment to experimentally show that our method performs
better than a pre-sequenced approach and a state of the art ON method extended
to MultiON
A mixed phenoxo and end-on azide bridged dinuclear copper(ii) Schiff base complex: synthesis, structure, magnetic characterization and DFT study
A dinuclear copper(II) complex, [(H2O)Cu(L)(μ1,1-N3)Cu(L)]ClO4 [HL = (2-(2-(ethylamino)ethylimino)methyl)-6-ethoxyphenol] has been synthesized and characterized by spectral and elemental analyses. The structure has been confirmed by single crystal X-ray diffraction. Variable temperature (2–300 K) magnetic susceptibility measurements indicate the presence of antiferromagnetic exchange coupling between the copper(II) centers (J = −46.18 cm−1), as also corroborated by DFT calculations (Jtheo = −45.98 cm−1). The calculated spin densities at the copper(II) centers were +0.56 and −0.61, confirming that they are the magnetic centers. An experimental absorption spectrum of the complex has been compared with a normalized absorption spectrum obtained theoretically. Supramolecular interactions in the solid state of the complex have also been characterized with the help of Hirshfeld analysis and the AIM theory