Quantum chemical insight into molecular structure, NBO analysis of the hydrogen-bonded interactions, spectroscopic (FT–IR, FT–Raman), drug likeness and molecular docking of the novel anti COVID-19 molecule 2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluorophenyl)acetamide - dimer

Abstract

Novel antiviral active molecule 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro- phenyl)acetamide has been synthesised and characterized by FT-IR and FT-Raman spectra. The equilibrium geometry, natural bond orbital calculations and vibrational assignments have been carried out using density functional B3LYP method with the 6-311G++(d,p) basis set. The complete vibrational assignments for all the vibrational modes have been supported by normal coordinate analysis, force constants and potential energy distributions. A detailed analysis of the intermolecular interactions has been performed based on the Hirshfeld surfaces. Drug likeness has been carried out based on Lipinski's rule and the absorption, distribution, metabolism, excretion and toxicity of the title molecule has been calculated. Antiviral potency of 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro-phenyl) acetamide has been investigated by docking against SARS-CoV-2 protein. The optimized geometry shows near-planarity between the phenyl ring and the pyrimidine ring. Differences in the geometries due to the substitution of the most electronegative fluorine atom and intermolecular contacts due to amino pyrimidine were analyzed. NBO analysis reveals the formation of two strong stable hydrogen bonded N–H···N intermolecular interactions and weak intramolecular interactions C–H···O and N–H···O. The Hirshfeld surfaces and consequently the 2D-fingerprint confirm the nature of intermolecular interactions and their quantitative contributions towards the crystal packing. The red shift in N–H stretching frequency exposed from IR substantiate the formation of N–H···N intermolecular hydrogen bond. Drug likeness and absorption, distribution, metabolism, excretion and toxicity properties analysis gives an idea about the pharmacokinetic properties of the title molecule. The binding energy −8.7 kcal/mol of the nonbonding interaction present a clear view that 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro- phenyl) acetamide can irreversibly interact with SARS-CoV-2 protease.

Molecular modeling of potent novel sulfonamide derivatives as non-peptide small molecule anti-COVID 19 agents

“…There is also a close correlation between dimer formation and the enzyme catalytic activity. A flip-flop mechanism is proposed for Mpro in which its two subunits are alternately used in acylation and deacylation steps (Mary et al., 2021 ). Details of M10 and SARS- CoV-2 Mpro is given below.…”

“…Darunavir is a sulfonamide derivative being considered as a possible treatment for SARS-CoV-2, clinical trials are underway (Harrison, 2020 ). Other sulfonamide derivatives are also being used in in silico studies (Calligari et al., 2020 ; Mary et al., 2021 ). Imidazole is a nitrogen-containing heterocyclic ring that possesses biological and pharmaceutical importance.…”

Recent investigations into synthesis and pharmacological activities of phenoxy acetamide and its derivatives (chalcone, indole and quinoline) as possible therapeutic candidates

“…Therefore, special attention has also been given to acetamide medications because of their possible use as a therapeutic agent. Acetamide derivatives and their analogs representing a high potential of biological activities including anti-inflammatory [ 63 ], anti-oxidant [ 64 ], anti-cancer [ 65 ], anti-convulsant [ 66 ], anti-hypoxic and anti-microbial [ 67 ], antituberculosis agents [ 68 ] and anti-COVID-19 molecules [ 69 ]. In addition, several acetamide derivatives are used to improve some enzymes that inhibit HIV virus activity from replicating [ 70 ].…”

“…Many chalcones also can be obtained via coupling reactions by using different reactants (63)(64)(65)(66)(67)(68)(69). Several reactions involved C-C and C-heteroatom covalent bond via oxidative addition transmetalation-reductive elimination, as illustrated in Scheme 12 [93].…”

Design and Manufacturing Optoelectronic Sensors for the Measurement of Refractive Index Changes under Unknown Polarization State

“…This is undoubtedly due to the dynamic advances in optical techniques [3][4][5], which include specialties such as spectroscopic and imaging techniques. Among many, the most promising seem to be high-resolution microscopy techniques [6,7], surface plasmon resonance [8][9][10], Fourier transform infrared spectroscopy [11], near-infrared spectroscopy [12], light emission caused by electronic relaxation techniques (fluorescence) [13][14][15][16], and Raman spectroscopy [17,18].…”