Synthesis of Functionalized Thiophene Based Pyrazole Amides via Various Catalytic Approaches: Structural Features through Computational Applications and Nonlinear Optical Properties

In the present study, pyrazole-thiophene-based amide derivatives were synthesized by different methodologies. Here, 5-Bromothiophene carboxylic acid (2) was reacted with substituted, unsubstituted, and protected pyrazole to synthesize the amide. It was observed that unsubstituted amide (5-bromo-N-(5-methyl-1H-pyrazol-3-yl)thiophene-2-carboxamide (7) was obtained at a good yield of about 68 percent. The unsubstituted amide (7) was arylated through Pd (0)-catalyzed Suzuki–Miyaura cross-coupling, in the presence of tripotassium phosphate (K3PO4) as a base, and with 1,4-dioxane as a solvent. Moderate to good yields (66–81%) of newly synthesized derivatives were obtained. The geometry of the synthesized compounds (9a–9h) and other physical properties, like non-linear optical (NLO) properties, nuclear magnetic resonance (NMR), and other chemical reactivity descriptors, including the chemical hardness, electronic chemical potential, ionization potential, electron affinity, and electrophilicity index have also been calculated for the synthesized compounds. In this study, DFT calculations have been used to investigate the electronic structure of the synthesized compounds and to compute their NMR data. It was also observed that the computed NMR data manifested significant agreement with the experimental NMR results. Furthermore, compound (9f) exhibits a better non-linear optical response compared to all other compounds in the series. Based on frontier molecular orbital (FMO) analysis and the reactivity descriptors, compounds (9c) and (9h) were predicted to be the most chemically reactive, while (9d) was estimated to be the most stable among the examined series of compounds.

Download Full-text

Therortical Studies and Investagting of Selected Potnet CDK2 Inhibitors as Anticancer Agents

10.21203/rs.3.rs-1044760/v1 ◽

2021 ◽

Author(s):

Mohammad J Abunuwar ◽

Adnan A Dahadha

Keyword(s):

Anticancer Agents ◽

Density Functional ◽

Chemical Potential ◽

Chemical Reactivity ◽

Three Dimensional ◽

Data Bank ◽

Basis Set ◽

Chemical Hardness ◽

Cyclin Dependent Kinase ◽

Reactivity Descriptors

Abstract In this study eight selected of the most potent cyclin dependent kinase 2 inhibitors in which targeting adenosine triphosphate -pocket site theoretically investigated to support literature information of frontier molecular orbitals, molecular electrostatic maps, and global chemical reactivity descriptors such as chemical hardness, chemical softness, chemical potential, electronegativity and electrophilicity of cyclin dependent kinase 2 inhibitors. Calculation and three-dimensional plotting were achieved through Gaussian 09W and Gausview 6 software’s utilizing density functional theory quantum modeling applying both hybrids extended and not extended basis set. Crystal structure of CDK2 with inhibitors was obtained from protein data bank and visualized through PyMol Schrödinger software to assign polar and non-polar interactions of inhibitors with enzyme. A promising conclusion trend obtained in this research regarding to molecules that could have an inhibition activity toward the cyclin dependent kinase 2 enzymes. Our theoretical investigation emphasizes that, the anti-cancer activity has directly relationship with value of chemical hardness and chemical softness, where the most potent compounds was the pyrazolopyrimidine and imidazole pyrimidine and they have higher chemical hardness value and at the same time lower value of chemical softness compared with the rest of compounds.

Download Full-text

Reactivity and Stability of Metalloporphyrin Complex Formation: DFT and Experimental Study

Molecules ◽

10.3390/molecules25184221 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4221 ◽

Cited By ~ 1

Author(s):

Rimadani Pratiwi ◽

Slamet Ibrahim ◽

Daryono H. Tjahjono

Keyword(s):

Lower Energy ◽

Chemical Potential ◽

Chemical Reactivity ◽

Binding Constants ◽

Stable Complex ◽

Chemical Hardness ◽

Reactivity Descriptors ◽

Chemical Reactivity Descriptors ◽

Electronic Chemical Potential ◽

Electronic Chemical

The interaction of three cationic porphyrins—meso-tetrakis (N-methylpyridinium-4-yl) porphyrin (TMPyP), meso-tetrakis (1,3-dimethylimidazolium-2-yl) porphyrin (TDMImP), and meso-tetrakis (1,2-dimethylpyrazolium-4-yl) porphyrin (TDMPzP)—with five heavy metals was studied computationally, and binding constants were calculated based on data obtained by an experimental method and compared. The reactivity and stability of their complexes formed with lead, cadmium, mercury, tin, and arsenic ions were observed in DFT global chemical reactivity descriptors: the electronic chemical potential (µ), chemical hardness (η), and electrophilicity (ω). The results show that M-TDMPzP has higher chemical hardness and lower electrophilicity compared to M-TMPyP and M-TDMImP, indicating the reaction of TDMPzP with metals will form a more stable complex. Specifically, Cd-TDMPzP complexes can stabilize the system, with a lower energy and electronic chemical potential, higher chemical hardness, smaller electrophilicity, and higher binding constant value compared to Pb-TDMPzP and Hg-TDMPzP. This result suggests that the interaction of the Cd2+ ion with TDMPzP will produce a stable complex.

Download Full-text

DFT study and microbiology of some coumarin-based compounds containing a chalcone moiety

Journal of the Serbian Chemical Society ◽

10.2298/jsc130628077s ◽

2014 ◽

Vol 79 (4) ◽

pp. 435-443 ◽

Cited By ~ 14

Author(s):

Selma Spirtovic-Halilovic ◽

Mirsada Salihovic ◽

Hurija Dzudzevic-Cancar ◽

Snezana Trifunovic ◽

Suncica Roca ◽

...

Keyword(s):

Chemical Potential ◽

Chemical Reactivity ◽

Antibacterial Activities ◽

Chemical Hardness ◽

Reactivity Descriptors ◽

Bacillus Subtilis Atcc ◽

Chemical Reactivity Descriptors ◽

Electronic Chemical Potential ◽

Electronic Chemical

In the present investigation, a series of coumarin-based compounds containing a chalcone moiety were studied for their in vitro and in silico properties. DFT global chemical reactivity descriptors (chemical hardness, total energy, electronic chemical potential and electrophilicity) are calculated for four synthesized compounds and used to predict their relative stability and reactivity. The antibacterial activities of all compounds have been screened against Bacillus subtilis (ATCC No. 6633) and Bacillus cereus (ATCC No. 11778). Quantum-chemical calculations indicate that antibacterial activity correlates well with chemical reactivity descriptors of molecules.

Download Full-text

DFT investigations on arylsulphonyl pyrazole derivatives as potential ligands of selected kinases

Open Chemistry ◽

10.1515/chem-2020-0135 ◽

2020 ◽

Vol 18 (1) ◽

pp. 857-873

Author(s):

Kornelia Czaja ◽

Jacek Kujawski ◽

Radosław Kujawski ◽

Marek K. Bernard

Keyword(s):

Free Energy ◽

Molecular Orbital ◽

Density Functional ◽

Chemical Reactivity ◽

Chemical Hardness ◽

Free Energy Of Solvation ◽

Fukui Functions ◽

Reactivity Descriptors ◽

Condensed Fukui Functions ◽

Charge Partitioning

AbstractUsing the density functional theory (DFT) formalism, we have investigated the properties of some arylsulphonyl indazole derivatives that we studied previously for their biological activity and susceptibility to interactions of azoles. This study includes the following physicochemical properties of these derivatives: electronegativity and polarisability (Mulliken charges, adjusted charge partitioning, and iterative-adjusted charge partitioning approaches); free energy of solvation (solvation model based on density model and M062X functional); highest occupied molecular orbital (HOMO)–lowest occupied molecular orbital (LUMO) gap together with the corresponding condensed Fukui functions, time-dependent DFT along with the UV spectra simulations using B3LYP, CAM-B3LYP, MPW1PW91, and WB97XD functionals, as well as linear response polarisable continuum model; and estimation of global chemical reactivity descriptors, particularly the chemical hardness factor. The charges on pyrrolic and pyridinic nitrogen (the latter one in the quinolone ring of compound 8, as well as condensed Fukui functions) reveal a significant role of these atoms in potential interactions of azole ligand–protein binding pocket. The lowest negative value of free energy of solvation can be attributed to carbazole 6, whereas pyrazole 7 has the least negative value of this energy. Moreover, the HOMO–LUMO gap and chemical hardness show that carbazole 6 and indole 5 exist as soft molecules, while fused pyrazole 7 has hard character.

Download Full-text

Synthesis, Characterization, Catalytic Activity, and DFT Calculations of Zn(II) Hydrazone Complexes

Molecules ◽

10.3390/molecules25184043 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4043 ◽

Cited By ~ 1

Author(s):

Temiloluwa T. Adejumo ◽

Nikolaos V. Tzouras ◽

Leandros P. Zorba ◽

Dušanka Radanović ◽

Andrej Pevec ◽

...

Keyword(s):

Density Functional Theory ◽

Gas Phase ◽

Molecular Orbital ◽

Density Functional ◽

Chemical Potential ◽

Chemical Reactivity ◽

Geometry Optimization ◽

Coupling Reaction ◽

Functional Theory ◽

Reactivity Descriptors

Two new Zn(II) complexes with tridentate hydrazone-based ligands (condensation products of 2-acetylthiazole) were synthesized and characterized by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy and single crystal X-ray diffraction methods. The complexes 1, 2 and recently synthesized [ZnL3(NCS)2] (L3 = (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)ethan-1-aminium) complex 3 were tested as potential catalysts for the ketone-amine-alkyne (KA2) coupling reaction. The gas-phase geometry optimization of newly synthesized and characterized Zn(II) complexes has been computed at the density functional theory (DFT)/B3LYP/6–31G level of theory, while the highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO and LUMO) energies were calculated within the time-dependent density functional theory (TD-DFT) at B3LYP/6-31G and B3LYP/6-311G(d,p) levels of theory. From the energies of frontier molecular orbitals (HOMO–LUMO), the reactivity descriptors, such as chemical potential (μ), hardness (η), softness (S), electronegativity (χ) and electrophilicity index (ω) have been calculated. The energetic behavior of the investigated compounds (1 and 2) has been examined in gas phase and solvent media using the polarizable continuum model. For comparison reasons, the same calculations have been performed for recently synthesized [ZnL3(NCS)2] complex 3. DFT results show that compound 1 has the smaller frontier orbital gap so, it is more polarizable and is associated with a higher chemical reactivity, low kinetic stability and is termed as soft molecule.

Download Full-text

New molecular target insights about protein kinases of the Plasmodium falciparum. Using molecular docking and DFT-based reactivity descriptors

Journal of Theoretical and Computational Chemistry ◽

10.1142/s0219633617500766 ◽

2017 ◽

Vol 16 (08) ◽

pp. 1750076 ◽

Cited By ~ 1

Author(s):

Alejandro Morales-Bayuelo

Keyword(s):

Plasmodium Falciparum ◽

Protein Kinases ◽

Density Functional ◽

Chemical Potential ◽

Chemical Reactivity ◽

Binding Pocket ◽

Fukui Functions ◽

Reactivity Descriptors ◽

Chemical Reactivity Descriptors ◽

Hinge Zone

Currently, there is increasing interest in the potential of malaria inhibitors in Plasmodium falciparum activity. In this work, is propose a possible alternative to classifying 154 antimalarials, with P. falciparum activity. These antimalarials were synthesized by the Chibale’s group ( http://www.kellychibaleresearch.uct.ac.za/ ), with the goal of finding new insights on the binding pocket of the protein kinase PfPK5, PfPK7, PfCDPK1, PfCDPK4, PfMAP1, and PfPK6 of the malaria parasite. However, there is only information about crystallography of PfPK5 and PfPK7. The protein kinases PfCDPK1, PfCDPK4, PfMAP1, and PfPK6 were modeled using molecular homology. The validation used shows that our homology models can be an alternative for the protein kinases from P. falciparum, unknown today. The antimalarials were classified by taking into account the interactions in the hinge zone. These ligands bind to the kinase through the formation of one of two hydrogen bonds, with the backbone residues of the hinge region connecting the kinase N- and C-terminal loops. These interactions were supported by a reactivity chemistry analysis, using global chemical reactivity descriptors such as chemical potential, hardness, softness, electrophilicity, and the Fukui functions as local reactivity descriptors, within the Density Functional Theory (DFT) context.

Download Full-text

Rutile Molecular Model and its EUC Determination by PM7

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.976.260 ◽

2014 ◽

Vol 976 ◽

pp. 260-264

Author(s):

C.H. Rios-Reyes ◽

Luis Humberto Mendoza Huizar ◽

Juan Coreño-Alonso

Keyword(s):

Band Gap ◽

Electronic Properties ◽

Chemical Potential ◽

Molecular Model ◽

Theoretical Calculations ◽

Chemical Reactivity ◽

Total Hardness ◽

Physical Parameters ◽

Reactivity Descriptors ◽

Cluster Properties

Rutile surface has been modeled in order to study its electronic properties as well as to determine its surface chemical reactivity. There have been constructed 10 different rutile structures, from a 6 atoms cluster (for the smallest) to a 356 atoms cluster (for the biggest). It was calculated for each cluster some physical parameters which are related to the electronic properties, such as work function, band gap, and density of states (DOS), in order to analyze the tendency of the cluster properties with the increase of atoms. From the data obtained, it was determined the Electronic Unit Cell (EUC), which refers to the modeled structure for what the electronic and reactivity properties of the system does no change, from clusters with different number of atoms. From the rutile EUC cluster it was determined its band gap with a value of 3.28 eV, which agreed with the experimental value of 3.0-3.1 eV. Furthermore, it was performed a reactivity surface study, which comprised the analysis of reactivity descriptors such as ionization potential, electronic affinity, total hardness, electronic chemical potential, electrophilicity and electronegativity. All theoretical calculations were performed using the semiempirical PM7 included in the 2012 version of MOPAC and the surfaces were modeled from crystallographic data.

Download Full-text

Interactions in flavanone and chalcone derivatives: Hirshfeld surface analysis, energy frameworks and global reactivity descriptors

Acta Crystallographica Section C Structural Chemistry ◽

10.1107/s2053229620001503 ◽

2020 ◽

Vol 76 (3) ◽

pp. 212-224

Author(s):

Magdalena Małecka ◽

Lilianna Chęcińska ◽

Joachim Kusz ◽

Marta Biernacka ◽

Bogumiła Kupcewicz

Keyword(s):

Crystal Lattice ◽

Surface Analysis ◽

Chemical Potential ◽

Lattice Energy ◽

Hirshfeld Surface ◽

Hirshfeld Surface Analysis ◽

Chemical Hardness ◽

Reactivity Descriptors ◽

Chalcone Derivatives ◽

Global Reactivity Descriptors

The present study examines a series of flavanone and chalcone derivatives substituted with electron-withdrawing groups (Cl or Br) and electron-donating groups (OH, CH3 and OCH3), namely, 7-methoxy-2-phenyl-3,4-dihydro-2H-1-benzopyran-4-one, C16H14O3, 2-(4-methoxyphenyl)-3,4-dihydro-2H-1-benzopyran-4-one, C16H14O3, 2-(4-methoxyphenyl)-6-methyl-3,4-dihydro-2H-1-benzopyran-4-one, C17H16O3, 2-(4-chlorophenyl)-3,4-dihydro-2H-1-benzopyran-4-one, C15H11ClO2, 8-bromo-6-methyl-2-phenyl-3,4-dihydro-2H-1-benzopyran-4-one, C16H13BrO2, (2E)-1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one, C16H14O3, and (2E)-1-(2-hydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one, C15H12O3. It compares the two groups of derivatives with regard to their intermolecular interactions in the crystal lattice and lattice energy calculations, together with energy framework visualization and global reactivity descriptors (chemical hardness, chemical potential and electrophilicity index). It also discusses the relationships between different noncovalent interactions derived from Hirshfeld surface analysis, crystal lattice energy and global reactivity descriptors of the compounds.

Download Full-text

Topological Model on the Inductive Effect in Alkyl Halides Using Local Quantum Similarity and Reactivity Descriptors in the Density Functional Theory

Journal of Quantum Chemistry ◽

10.1155/2014/850163 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Alejandro Morales-Bayuelo ◽

Ricardo Vivas-Reyes

Keyword(s):

Density Functional ◽

Chemical Potential ◽

Inductive Effect ◽

Chemical Reactivity ◽

Topological Analysis ◽

Basis Set ◽

Organic Chemical ◽

Quantum Similarity ◽

Local Exchange ◽

Reactivity Descriptors

We present a topological analysis to the inductive effect through steric and electrostatic scales of quantitative convergence. Using the molecular similarity field based in the local guantum similarity (LQS) with the Topo-Geometrical Superposition Algorithm (TGSA) alignment method and the chemical reactivity in the density function theory (DFT) context, all calculations were carried out with Amsterdam Density Functional (ADF) code, using the gradient generalized approximation (GGA) and local exchange correlations PW91, in order to characterize the electronic effect by atomic size in the halogens group using a standard Slater-type-orbital basis set. In addition, in this study we introduced news molecular bonding relationships in the inductive effect and the nature of the polar character in the C–H bond taking into account the global and local reactivity descriptors such as chemical potential, hardness, electrophilicity, and Fukui functions, respectively. These descriptors are used to find new alternative considerations on the inductive effect, unlike to the binding energy and dipole moment performed in the traditional organic chemical.

Download Full-text

Computational Design, Spectral, NBO, DOS, Bioactivity Evaluation, ADMET Analysis, Third-Order non-linear Optical and Quantum Chemical Investigations on Hydrogen Bonded Novel Organic Molecular Complex of 4-[Bis[2-(acetyloxy)ethyl]amino]benzaldehyde (4B2AEAB) Derivatives for Opto-Electronic Applications

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22838 ◽

2020 ◽

Vol 32 (11) ◽

pp. 2793-2820

Author(s):

Ashutosh Kumar ◽

Anil Mishra

Keyword(s):

Gas Phase ◽

Function Analysis ◽

Chemical Reactivity ◽

Computational Design ◽

Basis Set ◽

Mulliken Charge ◽

Water Solvent ◽

Non Linear ◽

Linear Optical ◽

Vibrational Wavenumbers

In this paper, the authors reported a theoretical investigation on molecular structure, geometry optimization, global and local chemical reactivity descriptors calculations, NBO study, DOS, non-linear optical behaviour and vibrational wavenumbers of the novel 4-[bis[2- (acetyloxy)ethyl]amino]benzaldehyde (4B2AEAB) were carried out by DFT (B3LYP and B3PW91) methods with 6-31+G (d, p) basis set in water solvent. The calculated vibrational wavenumbers are found to be in good agreement with experimental FT-IR spectra and PED analysis using GaussView 5.0 and VEDA 4 program. The UV-Vis absorption spectrum of 4B2AEAB was calculated by using TD-DFT/B3LYP/6-31+G(d,p) in gas phase, water, CHCl3, DMSO and CH2Cl2 solvents using CPCM model and λmax in range of 354.16, 341.35, 343.74, 342.18 and 342.64 nm, respectively. The density of state (DOS spectrum) of the compound in term of HOMOs and LUMOs and MESP were calculated and analyzed. The temperature effects on the thermodynamic properties are also discussed. The calculated 1H NMR and 13C NMR chemical shift using GIAO method and solvent effect are investigated by B3LYP/6-31+G(d,p) in gas phase, chloroform, water, DMSO and CH2Cl2 solvents and correlate with experimental chemical shifts. The dipole moment, polarizability and the first static hyperpolarizability values show that the 4B2AEAB molecule is active non-linear optical (NLO) material. The nucleophilic and electrophilic reactive sites in the 4B2AEAB and its derivatives were analyzed by Fukui function analysis using Mulliken charge. The charge transfer, conjugative interactions and delocalization of electron density are analyzed by natural bond orbital (NBO) analysis. The biological properties and ADMET study of 4B2AEAB and its derivatives are also discussed.

Download Full-text