Category Archives: Journal of Physical Organic Chemistry

Molecular docking, synthesis, anticancer activity, and computational investigations of thiazole‐based ligands and their Cu(II) complexes

Posted on 24 May 2022 by nPreeti Jain, nMridula Guin, nAnindita De, nMegha Singhn

Synthesis and characterization of two mononuclear copper (II) complexes with newly explored thiazole derivatives and their structure optimization using DFT calculation were carried out. Molecular docking study of synthesized molecules was performed against EGFR kinase and tyrosine kinase molecular targets, which were further verified by doing in vitro anticancer activity analysis.

Abstract

Present work describes the preparation of Schiff base ligands named 2-methoxy-6-[(E)-(1,3-thiazol-2-ylimino) methyl] phenol and its structure and activity comparison with another Schiff base N-[(E)-pyridin-2-ylmethylidene]-1,3-thiazol-2-amine. Cu(II) complex of both the ligands were prepared in 2:1 ratio in basic medium. UV-Vis, FTIR, NMR spectroscopy, and other physicochemical techniques were used for characterization of synthesized compounds. The FTIR spectra of the ligands and their Cu(II) complexes evident the tetra dentate behavior of ligands and indicates the presence of nitrate groups. The geometry of synthesized ligands and complexes was optimized using density functional theory (DFT) with hybrid B3LYP functional. It confirms that the Cu(II) metal surrounded by tetra dentate ligand moiety was coordinated with oxygen atom of one nitrate group with bond lengths of 1.9668 Å for complex 1 and 2.2420 Å and 2.6220 Å for complex 2. Molecular docking study of synthesized molecules was performed against EGFR kinase (PDB:1m17) and tyrosine kinase (PDB:1 t46) molecular targets. The complex 1 has shown maximum inhibition with a binding energy of −10.40 kcal/mol against 1t46 molecular target. Further, ligand and complexes were analyzed by ADMET study, drug likeness, and bioactivity score by using online servers. Since these studies provided very significant results in terms of their binding energy with the target molecules and drug likeness score, time-dependent in vitro anticancer activity of all compounds was also tested by using MTT assay against SCC4 cancer cell line. Complex 1 has shown promising activity with an IC₅₀ value of 31.1 μM at 72 h time interval.

Variation in electrophilicity on electronic excitation

Posted on 16 May 2022 by nShanti Gopal Patra, nHimangshu Mondal, nPratim Kumar Chattarajn

The validity of the minimum electrophilicity principle is tested in the course of molecular electronic excitation.

Abstract

The rationality of the minimum electrophilicity principle (MElP) as a companion of minimum polarizability principle and maximum hardness principle is studied for simple diatomic, triatomic, and tetratomic molecules. The applicability is further justified considering organic molecules (e.g., pyrene and acridine yellow) are known for their photophysical properties and accordingly their excited state properties. Single excitation CI (CIS) and time-dependent density functional theory (TDDFT) are employed to study the excited state reactivity. Two types of excitations, namely vertical and adiabatic, are considered. Processes involving conservation and change in spin multiplicity are included during excitation. The general trend is that the molecules are less electrophilic in the ground state than those in the corresponding excited states. It is found that adiabatic excitation validates the principle even for the triplet ground state molecules undergoing an excitation where spin multiplicity gets altered. The TDDFT method explains the validity of the MElP augmenting the CIS method. This study echoed the MElP during molecular electronic excitation.

Can van der Waals constants be used in the chemical reactivity analysis? A new approach as a support to minimum magnetizability principle

Posted on 6 April 2022 by nSavaş Kaya, nSelçuk Şimşekn

A new equation to calculate the magnetic susceptibility of molecular systems is derived. It is proved that van der Waals constants are minimized in stable states Van der Waals constants are measures of the reactivity.

Abstract

One of the most important purposes of theoretical chemists is to derive new, useful, and reliable equations to compute the well-known parameters like hardness, polarizability, magnetizability, and electrophilicity providing enough hints for the reactivity analysis of the chemical systems. In the derivation of such equations, our research team widely considers the popular electronic structure rules like electronegativity equalization, maximum hardness, minimum polarizability, minimum magnetizability, and minimum electrophilicity principles. Recently, in the light of maximum entropy and minimum magnetizability principles, Kaya and Chattaraj (2021) presented a simple way to calculate their standard absolute entropies (S ⁰ ₂₉₈) based on molar diamagnetic susceptibilities (χ _m ) of inorganic ionic systems. In the present paper, a new and useful molar diamagnetic susceptibility calculation method including the use of van der Waals constants (a and b) is introduced. Here, we named this method as Kaya–Şimşek approach. Through the relations between molar diamagnetic susceptibility and van der Waals constants, we can easily predict the magnetic susceptibility of molecules that their magnetic susceptibilities are unknown. The results of the equations derived are quite close to experimentally reported data. The analyses made proved that van der Waals constants can be considered as chemical reactivity descriptors. We propose that in stable states, van der Waals constants are minimized. The validity of minimum magnetizability principle is supported with solid evidences.

The synergetic and multifaceted nature of carbon–carbon rotation reveals the origin of conformational barrier heights with bulky alkane groups

Posted on 5 April 2022 by nXinjie Wan, nXin He, nMeng Li, nBin Wang, nChunying Rong, nShubin Liun

This work examines the nature of the rotation barrier of exceedingly long carbon–carbon bonds for nine dimeric models with bulky alkane groups using density-based energy partition and information-theoretic approach. Many factors come into play and the generation of rotation barrier heights is synergetic and multifaceted. Our results invalidate that their stability comes from dispersion forces and confirm that the dominant factor is the electrostatic interaction but contributions from steric and exchange-correlation effects are minor yet indispensable.

Abstract

Designing compounds with as long carbon–carbon bond distances as possible to challenge conventional chemical wisdom is of current interest in the literature. These compounds with exceedingly long bond lengths are commonly believed to be stabilized by dispersion interactions. In this work, we build nine dimeric models with varying sizes of alkyl groups, let the carbon–carbon bond flexibly rotate, and then analyze rotation barriers with energy decomposition and information-theoretic approaches in density functional theory. Our results show that these rotations lead to extraordinarily elongated carbon–carbon bond distances and rotation barriers are synergetic and multifaceted in nature. The dominant factor contributing to the relative stability of the dimers with bulky alkane groups is not the dispersion force but the electrostatic interaction with steric and exchange-correlation effects playing minor yet indispensable roles.

Direct dynamics simulation of the thermal O(3P) + dimethylamine reaction in the triplet surface. I. Rate constant and product branching

Posted on 8 March 2022 by nDebdutta Chakraborty, nWilliam L. Hasen

Corresponding to the collision energy of 7.8 kcal/mol, the reaction between O(3P) and dimethylamine leads to two product channels, namely, (1) ²OH and ²CH₃NHCH₂ (major product) and (2) ²OH and ²CH₃NCH₃ (minor product). Both pathways follow direct and indirect H abstraction mechanisms.

Abstract

In order to provide atomistic details for the mechanism of the collisional dynamics of O(³P) and dimethylamine (DMA) in the triplet electronic surface, direct dynamics simulations are reported herein. The simulations are performed at the U-HSE06/aug-cc-pVDZ level of theory. The results are reported for the relative collision energy of 7.8 kcal/mol. For the vibrational and rotational excitations, following temperature regimes have been considered: 200 and 10 K, respectively. Simulations reveal that the reaction can lead to two product channels in the considered energy regime: (1) ²OH + ²CH₃NHCH₂ and (2) ²OH + ²CH₃NCH₃. The computed reaction cross section for pathways 1 and 2 are as follows: 17.89  ± 0.20 Ų and 3.28  ± 0.03 Ų, whereas the computed microcanonical reaction rate constants for pathways 1 and 2 are as follows: (4.21  ± 0.05)*10⁻¹⁰ and (7.72  ± 0.07)*10⁻¹¹ cm³/(molecule sec). Both pathways follow direct and indirect H abstraction processes. Among the direct pathways, stripping and rebound mechanisms have been observed, whereas the indirect pathway involves formation of a post-reaction complex having lifetime ~0.4–0.5 ps. The velocity scattering angle distribution for the reaction is dominated by scattering in the sideways (60–120 °) and backward (120–180 °) directions with some contribution from the scattering in the forward direction (0–60 °).

Fischer and Schrock carbene complexes in the light of global and local electrophilicity‐based descriptors

Posted on 19 February 2022 by nShanti Gopal Patra, nRuchi Jha, nHimangshu Mondal, nPratim Kumar Chattarajn

The electrophilic nature of Fischer carbene and nucleophilic nature of Schrock carbene are understood through philicity.

Abstract

The carbon atom (carbene) of Fischer and Schrock complexes are electrophilic and nucleophilic, respectively. The reactivity index electrophilicity is a global reactivity parameter and can tell only about the total electrophilicity of the complexes. To differentiate between the reactivity patterns of these two carbenes, the philicity and multiphilic descriptor are calculated. In Fischer complexes, it is found that the philicity of the nucleophilic attack (ωC+) is higher than that of philicity of the electrophilic attack (ωC−) implying the electrophilic nature. A reverse order is found in the Schrock complex pointing nucleophilic character. The multiphilic descriptor (Δω _C  =  ωC+  −  ωC−) is found to be positive in Fischer but negative in Schrock leading to the same conclusion. Fischer carbene complexes having general formula (CO)₅Cr═CH-R (R = CH₃, Ph, CCH, CH═CH₂, OCH₃, OH, NHCH₃, and NH₂) the order of ωC+ and Δω _C better describe the trend. The trend has been justified through energy decomposition in the purview natural orbital for chemical valence (EDA-NOCV) analysis owing to the π contribution from the R group. The change in the reactivity patterns along the intrinsic reaction coordinate of two representative reactions is plotted. This way of understanding the reactivity parameters would help experimental chemists to predict the catalytic application of carbene complexes of transition metal without the classification of Fischer and Schrock type.

Ligand effect on the stability, reactivity, and acidity of imidazolium systems

Posted on 8 February 2022 by

Conceptual density functional theory (CDFT) provides valuable insights about the ligand effect on the stability, reactivity of imidazolium and NHC systems. The pKa of imidazolium can predict the suitable base used for the generation of NHC from imidazolium system.

Abstract

Imidazolium and its different N-substituted derivatives are considered in this study to investigate their stability, reactivity, and acidity. Different aliphatic and aromatic ligands have been introduced in imidazolium to see their effect. It has been observed that the acidity of imidazolium systems increases with ligands having higher electron-withdrawing nature. The studied systems are found to be weak acids, and weak bases can generate the corresponding carbene systems. The stability, reactivity, and aromaticity of all the systems are analyzed by using conceptual density functional theory (CDFT)-based reactivity descriptors. Nucleus-independent chemical shift (NICS) values lend additional support for the aromatic behavior of the studied molecules.