Molecular Electrostatic Potential Research Articles

3-Pyrazolyl-pyran-2-one: Synthesis, crystal structure, Hirshfeld surface analysis, DFT and ADME studies

Synthesis, crystal structure, Hirshfeld surface analysis, DFT and in-silico studies were carried out for the 4‑hydroxy-6-methyl-3-(1-phenyl-1H-pyrazol-3-yl)-2H-pyran-2-one 2. The reaction efficiency was evaluated performing two conditions to prepare the Vilsmeir-Haack reagent: phosphoryl trichloride in DMF and phosphorus pentachloride in DMF. The molecular structure was confirmed by 1H and 13C NMR, IR spectroscopy and X-ray diffraction analysis. The pyrazole and pyran rings are nearly coplanar. The molecules are connected through C—H···O hydrogen bonds, C—H⋯π and π⋯π stacking interactions, forming layers in the crystal lattice. Hirshfeld surface analysis for crystal packing indicates that the most important contributions are H⋯H (41.6 %), C⋯H/H⋯C (22.6 %), O…H/H…O (20.9 %) interactions. The frontier molecular orbital, Mulliken and QTAIM atomic charge, Molecular Electrostatic Potential, Natural Bond Orbitals were produced using the optimized structure by B3LYP/6–311G(d,p) level of theory. The calculated LUMOHOMO gap (4.261 eV) indicated that the eventual charge transfer and showed chemical reactivity. Intrinsic reaction coordinate (IRC) calculation confirm that the transition state connects the reactants to the products. The experimental geometry parameters of the title compound are compared with the geometry of the optimized molecule in the gas phase and found in good agreement. The crystal structure was further explored to define the interaction energy between the molecular pairs. The ADME profile that pyrazolyl-pyran-2-one 2 is an inhibitor of CYP1A2 one of the five key cytochrome isoforms enzymes involved in drug metabolism.

Effect of the central atom and donor on linear and nonlinear optical properties of tricyanopyrrolidone derivatives: DFT and TD-DFT approach

We have designed 50 molecules having “donor-π-acceptor system.” Different donors connected to tricyanopyrrolidone acceptor with 10 different heteroatom units are selected to study their “ground state” structural and nonlinear optical (NLO) properties. Frontier molecular orbital (FMO), molecular electrostatic potential (MEP) plots, and bond length alteration (BLA) showed intramolecular charge transfer (ICT). Results suggest that HOMO-LUMO energies of selected dyes depend on donor strength and heteroatoms. Triphenylamine substituted donors showed red-shifted vertical excitations, higher dipole moments, and higher hyperpolarizabilities. Using DFT, NLO parameters such as (β0) and (γ) are calculated with three different functionals, including global hybrid (GH), B3LYP and range separated CAM-B3LYP, and ωB97XD functionals. Molecular reactivity descriptors, chemical potential (μ), chemical hardness (η), electrophilicity index (ω), and hyperhardness (Γ) are produced. DFT descriptors are correlated with calculated NLO parameters.

Crystal structure elucidation of a geminal and vicinal bis(trifluoromethanesulfonate) ester.

Geminal and vicinal bis(trifluoromethanesulfonate) esters are highly reactive alkylene synthons used as potent electrophiles in the macrocyclization of imidazoles and the transformation of bypyridines to diquat derivatives via nucleophilic substitution reactions. Herein we report the crystal structures of methylene (C3H2F6O6S2) and ethylene bis(trifluoromethanesulfonate) (C4H4F6O6S2), the first examples of a geminal and vicinal bis(trifluoromethanesulfonate) ester characterized by single-crystal X-ray diffraction (SC-XRD). With melting points slightly below ambient temperature, both reported bis(trifluoromethanesulfonate)s are air- and moisture-sensitive oils and were crystallized at 277 K to afford two-component non-merohedrally twinned crystals. The dominant interactions present in both compounds are non-classical C-H...O hydrogen bonds and intermolecular C-F...F-C interactions between trifluoromethyl groups. Molecular electrostatic potential (MEP) calculations by DFT-D3 helped to quantify the polarity between O...H and F...F contacts to rationalize the self-sorting of both bis(trifluoromethanesulfonate) esters in polar (non-fluorous) and non-polar (fluorous) domains within the crystal structure.

Synthesis, crystal structure, spectroscopic characterization, in vitro, molecular docking and DFT studies of 1- (Tert-Butyl) 2-methyl (2S, 4R)-4-hydroxy pyrrolidine-1,2-dicarboxylate

A chiral pyrrolidine-based compound, namely 1-(Tert-Butyl) 2-Methyl (2S, 4R)-4-Hydroxy Pyrrolidine-1,2-Dicarboxylate (NHP), was synthesized and crystallized by the slow evaporation technique. NMR, FT-IR, ESI-MS, UV–visible spectroscopy, and elemental analysis designate the molecule. The molecule crystallized in the orthorhombic space group P212121, identified by X-ray diffraction (XRD). Quantum chemical calculations were performed using DFT at the B3LYP/6–311++G (d,p) level. The DFT-calculated optimal structural parameters and the XRD-derived parameters showed a good correlation. The frequency of NHP is calculated using the DFT method and compared with observed results. The synthesized compound's molecular reactivity was further investigated using Mulliken atomic charges, HOMO-LUMO, and molecular electrostatic potential (MEP). The molecule was tested for molecular docking with bio-enzymes such as α-amylase (1HNY) and cyclooxygenases (1PGG & 4COX). The compound showed 7 hydrogen bonding interactions with 1HNY and 8 hydrogen bonding interactions with 4COX. The DFT investigations strongly support the molecular docking results. The molecule's in-vitro anti-inflammatory and anti-diabetic activity was compared with conventional medication. The NHP showed superior anti-inflammatory activity with protein denaturation technique than the standard diclofenac sodium. The results showed that the molecule outperformed the conventional medication in tests for inflammation.

Investigation of sensing behavior of carbon nitride (C6N8) for detection of phosphine (PH3) and phosphorous trichloride (PCl3): A DFT approach

AbstractThis study shows the exploration of the gas‐sensing capabilities of C6N8 material against toxic gases like phosphine (PH3) and phosphorous trichloride (PCl3). First‐principles study based on M05‐2X/LanL2DZ (d, p) method was performed to investigate the interaction energy (Eint.), frontier molecular orbitals (FMOs), natural bonding orbital (NBO), noncovalent interactions (NCIs), partial density of states (PDOS), molecular electrostatic potential (MEP), and quantum theory of atoms in molecules (QTAIM) analyses. The interaction energy results showed that PCl3@C6N8 (−23.45 kJ/mol) is more stable than PH3@C6N8 (−14.79 kJ/mol). A considerable decrease in the HOMO‐LUMO band gap of C6N8 was observed as a result of its complexation with the analytes. QTAIM and NCI analyses indicated the presence of weak noncovalent interactions between C6N8 and gases (PH3 and PCl3). SAPT0 analysis was performed to quantify the NCIs. MEP maps of complexes revealed the localization of electronic density on C6N8. The little recovery time of complexes (determined at 300 K) showed that C6N8 can serve as a reusable sensing material against PH3 and PCl3. Our results demonstrate that the C6N8 surface is a reliable material for detecting phosphine and phosphorous trichloride gases.

Theoretical designing of 9,9'-dicarbazole-based dye via end-group modification for indoor DSSC applications

Molecular modeling has garnered significant attention in the realm of organic solar cells (OSCs) because it holds the promise of producing more efficient OSCs with notably enhanced power conversion efficiency (PCE). In this quest, we have undertaken a strategic modification of the acceptor moieties within the recently synthesized metal-free dicarbazole-based organic dye Cz-2, resulting in five novel theoretical dyes, designated as PT1-PT5. Numerous simulations encompassed both the newly designed compounds and the reference (Cz-2) by using DFT and TD-DFT, a comprehensive characterization aimed at enhancing photovoltaic and optoelectronic properties. We probed into the analysis of ground state geometry, frontier molecular orbitals, transition density matrix, optical properties, density of state, binding energy, molecular electrostatic potential, reorganizational energy, open-circuit voltage, and fill factor. Our findings unveiled a common trend among all the theoretical dyes, a reduction in band gap (Eg), a notable red-shift in absorbance ranging from 434 nm to 554 nm, and lowered binding and excitation energy. The decreased reorganization energy i.e., λ e and λ h, spanning a range from 0.0040 to 0.0052 eV and 0.0043 to 0.0075 eV respectively, promised significantly enhanced charge mobility. Intriguingly, the binding energies of all the designed compounds consistently registered values lower than that of reference (R), with figures ranging from 0.55 to 0.64 eV, compared to the binding energy of R (0.67 eV). These dyes show significant potential for indoor photovoltaics as they can absorb light in the visible range for indoor renewable energy applications. Our comprehensive analyses suggest that PT1-PT5 are promising candidates with great potential for advancing the field of renewable energy.

Investigation of transition metals (Ag, Au, Pd, Pt and Ru)-doped boron nitride nanocarrier for drug delivery process of favipiravir: An intuition from DFT

The scientific community is keenly interested in developing efficient drug delivery systems using B12N12, particularly for carrying anti-influenza drugs like Favipiravir (FAV) against life-threatening RNA virus infections. This study delves into the exploration of transition metal-doped B12N12 nanostructures as potential carriers for drug delivery. Using density functional theory (DFT) calculations at the wB97XD/6-311++G(d,p) level of theory, the research specifically investigates the efficacy of transition metal-doped (Ag, Au, Pd, Pt, and Ru) boron nitride nanocages as effective agents for delivering the FAV drug. The systematic exploration of adsorption energy, electronic features, and thermodynamic properties (ΔG and ΔH) of FAV interacting with B12N12 and transition metals-doped (Ag, Au, Pd, Pt, and Ru) nanocages reveals a significant improvement in drug-carrying capacity, marked by notable physisorption capabilities as evident from negative adsorption energies. The confirmation of FAV’s interaction with doped-B12N12 nanocages was supported by a comprehensive analysis encompassing frontier molecular orbitals, adsorption energy, fractional charge transfer, molecular electrostatic potential (MEP), non-covalent interaction(NCI), and natural bond orbital (NBO) assessments. The frontier molecular orbitals (FMO), density of states (DOS), and natural bond orbital (NBO) analyses reveal nanocages as charge acceptors and drug as charge donor during the adsorption process. The band gap energies decreased upon FAV adsorption on both pristine and doped nanocages except Au and Pd doped nanocages. Among the doped cases, the Ag-doped B12N12 nanocage exhibits the most significant reduction in the HOMO-LUMO energy difference, and therefore should be the most effective nanocarrier for FAV. The results of this study offer novel insights for the development of B12N12 nanocages as carriers for the FAV drug.

Synthesis, antiproliferative, antibacterial activity of acridone derivatives: Experimental and theoretical calculations

A new ethyl 5-(2-(9-oxoacridin-10(9H)-yl)acetamido) thiophene-2-carboxylate (EATPC) and ethyl 2-(2-(9-oxoacridin-10(9H)-yl)acetamido)thiazole-5-carboxylate (EATZC) acridone derivatives were successfully synthesized and described using NMR, UV–Vis and FTIR spectroscopy approaches. The theoretical calculations were computed using Gaussian 09 W software employing DFT/TD-DFT/B3LYP methods with a basis set of 6–311+G (d,p). The calculated and observed spectroscopy results are compared and discussed, demonstrating the reliability of the developed structure of compounds. The natural bond orbital, molecular electrostatic potential, physicochemical descriptors and HOMO-LUMO energies were all calculated and thoroughly discussed in the present study. EATPC and EATZC were tested for antiproliferative capabilities against human breast cancer (MCF-7) cell lines by employing the MTT assay. Furthermore, molecular docking analyses were performed to determine the compound's most active binding sites to the target protein. The molecules EATPC and EATZC are docked with the 4E28 protein, yielding free binding energy energies of -7.8 and -7.9 kcal/mol. This study is unique in that it is the first in-depth report on the comprehensive biological and theoretical evaluation of these title compounds.

Mechanistic Analysis and Process Simulation of Ethyl Acetate-Ethanol Separation by Complex Solvent Extractive Distillation.

Developing high-performance solvents for extraction and optimizing process technologies is crucial for efficient extractive distillation (ED) separation of azeotrope mixtures. In this paper, computer-aided screening was used to study the ED of azeotrope mixtures in ethyl acetate and ethanol systems using organic solvent dimethyl sulfoxide (DMSO) and ionic liquid (IL) ([EMIM][Ac]). The structural relationship between the ILs and the azeotrope mixture was analyzed by σ-profile, molecular surface electrostatic potential, interaction energy, and separation gradient. Subsequently, process simulation was carried out using Aspen Plus software and global optimization was performed with genetic algorithm, which found that both traditional organic solvents and ILs have good separation effects. But considering the high volatility of organic solvents and low saturation vapor pressure of ILs, it is considered to combine them to further explore the cost and carbon emission advantages in extractive distillation separation. Compared with pure organic solvent and pure ILs separation processes, the TAC of the process using an IL-based mixed solvent process decreased by 5.11 and 21.98%, respectively. The carbon emissions of the mixed extractant process were slightly higher than those of the pure organic solvent process, but the addition of ILs made very little volatilization of organic solvents, saving a charge for extractant use. By improving the process, waste heat is effectively recovered, which can save most of the utility engineering costs, and compared with the previous process, the total alkali consumption and carbon dioxide emissions are reduced by 9.43 and 27.17%, respectively. This exploration provides a theoretical reference for the development application and industrial research of ED processes using IL-based mixed solvents.

Insights into oxidovanadium (3,4,5-trimethoxyphenyl) porphyrin: A comprehensive study of synthesis, crystal structure, Hirshfeld surface analysis and computational studies

The synthesis of Oxidovanadium 5,10,15,20-tetrakis(3,4,5-trimethoxyphenyl) porphyrin [VO(T(OMe)3PP)], complex 1, was successfully achieved and its structure was confirmed through single crystal analysis. This analysis revealed a deformed octahedral structure caused by the vanadium cation's interaction with six components, which includes a vanadyl oxygen atom. It is interesting that an oxygen atom from a methanol solvent molecule was discovered to fill an axial position in the arrangement. Further investigation involved the use of fingerprint plots and Hirshfeld surface analysis with dnorm mapping of complex 1. Significantly, interactions like H⋯H (62.4 %), O⋯H (11.8 %)/H⋯O (10.4 %), and C⋯H (7.4 %)/H⋯C(5.9 %) were emphasized in the Hirshfeld surface analysis. In addition, the Density Functional Theory (DFT) investigations, shows the HOMO-LUMO energy gap determined through experimentation in solvent closely correlated with the theoretically calculated energy difference of 0.96 eV for complex 1. Finally, Molecular Electrostatic Potential (MEP) analysis were performed.

A theoretical investigation of the competition between σ- and π-holes on the stability of the complexes resulting from the interaction between the COCl2 and OCY molecules (Y = S, Se, and Te)

Carbonyl dichloride (COCl2), also known as phosgene, is a highly toxic gas, whose exposure or acute inhalation causes severe respiratory complications, such as pulmonary edema, pulmonary emphysema, and even death. In this study, we theoretically investigated the complexes formed by the interaction between the COCl2 (phosgene) and OCY molecules (Y = S, Se, and Te). Complex geometry optimization yielded three distinct types of conformations. Conformation-I complexes were stabilized by two concurring chalcogen-bonding interactions (i.e. O⋯Y and Cl⋯Y) by forming a ring structure. However, only a single linear interaction (O⋯C) or (O⋯Cl) occurred in conformation-II and III complexes, forming complexes with the nature of tetrel and halogen bonds, respectively. According to the results of the molecular electrostatic potential (MEP), interaction energy (ΔET), natural bond orbital (NBO), and so on, the σ-hole of the Y atom in the OCY molecule exhibited higher acidic strength and formed more stable complexes than those resulting from the σ- and π-holes of the COCl2 molecule.

Synthesis, Crystal Structure, and DFT Studies on (E)-N'-((4-(4-(4-formyl-1-phenyl- 1H-pyrazol-3-yl)-5-methyl-1H-1,2,3-triazol-1-yl)phenyl)sulfonyl)-N,N-dimethylformimidamide

The title compound, (E)-N'-((4-(4-(4-formyl-1-phenyl-1H-pyrazol-3-yl)-5-methyl-1H-1,2,3-triazol-1-yl) phenyl)sulfonyl)-N,N-dimethylformimidamide (3), was obtained by performing the Vilsmeier- Haack reaction using 2.5 equiv. of phosphoryl chloride on compound 2a or 2b. The crystal structure of (E)-N'-((4-(4-(4-formyl-1-phenyl-1H-pyrazol-3-yl)-5-methyl-1H-1,2,3-triazol-1-yl)phenyl)sulfonyl)-N,N-dimethylformimidamide was determined from single-crystal X-ray diffraction. Quantum theoretical calculations for title structure were carried out by density functional theory (DFT/B3LYP/6-311++G** (2p, 2d). From the optimized structure, geometric parameters were obtained, experimental measurements were compared with the calculated data. Frontier molecular orbitals (FMOs), molecular electrostatic potential, and molecular properties, of the studied compound, were investigated by theoretical calculations.. KEYWORDS :The crystal structure, The quantum theoretical calculations, Pyrazole, Triazole, Molecular electrostatic potential.

Physical analysis of aspirin in different phases and states using density functional theory

This study analyzed the aspirin molecule (C9H8O4) using Density Functional Theory (DFT) on Gaussian 09W software. First, the structure of aspirin was optimized using the DFT method with the B3LYP functional and the 6-311+G (d,p) basis set. A global reactivity study was employed to understand the reactivity of aspirin in gas and solvent water for both anion and neutral states. To understand the involvement of orbitals in chemical stability and electron conductivity, we calculated the HOMO-LUMO. The thermodynamic function of a molecule was understood using thermochemistry. Molecular Electrostatic Potential (MEP) was employed to understand the physiochemical properties of aspirin. We observed the Mulliken atomic charge to calculate the atomic charge of aspirin. Finally, the title molecule's UV–Vis, FTIR, and Raman spectra are analyzed and compared with the experimental data.

Synthesis, crystal and molecular structure, DFT and antifungal activity studies of (E)-2-(3-methoxy-4-((6-(trifluoromethyl)pyrimidin-4-yl)oxy)styryl)-5-((2-(trifluoromethyl)benzyl)thio)-1,3,4-oxadiazole

Ferulic acid derivatives containing the 1,3,4-oxadiazole thioether and trifluoromethyl pyrimidine have displayed a wide array of pharmacological properties of interest to both medicinal and agricultural chemistry. This study focused on the synthesis of a new compound, (E)-2-(3‑methoxy-4-((6-(trifluoromethyl)pyrimidin-4-yl)oxy)styryl)-5-((2-(trifluoromethyl)benzyl)thio)-1,3,4-oxadiazole, with a ferulic acid skeleton, was synthesized via acetylation, condensation, cyclization, etherification, and thioetherification reactions. The title compound underwent comprehensive characterization using a variety of analytical techniques to gain a thorough insight into its molecular structure and properties. The structural arrangement of the compound was validated through X-ray diffraction and density functional theory calculations, while further analysis uncovered important physical and chemical attributes like molecular electrostatic potential and vibrational absorption bands. Moreover, the antifungal efficacy of the synthesized compounds was assessed, indicating their possible application in agriculture. This research lays the groundwork for the creation of novel compounds with antifungal properties.

Delving into 5-Amino-3-(4-chlorophenyl)-1-isonicotinoyl-2,3-dihydro-1H-pyrazole-4-carbonitrile ligand: Synthesis, spectroscopic (FT-IR, FT-Raman, NMR, UV- Vis), reactivity (ELF, LOL and Fukui), NCI, molecular docking and in silico ADMET studies by experimental and DFT methods

This paper talks about the preparation, characterization (FT-IR, FT-Raman, elemental, UV–Vis spectral, 1H NMR, and 13C NMR analysis) and DFT studies of ACLIDPC have been carried out. To clarify the molecule's reactivity, the molecular electrostatic potential (MEP), Local (Fukui) and global (HOMO-LUMO) reactive descriptor surface were determined. NBO analysis has shown that charge transfer and the spreading out of electron density within the molecule. Topology (NCI, ELF and LOL) analysis is used for studying the intermolecular interactions in ACLIDPC. Molecular docking with proteins (4O9I, 2HI9, and 2ZA5) has revealed the biological action of the antiviral, antiasthmatic and insulin-inhibiting activities. Drug likeness, ADME/Tox and other physicochemical properties were also studied.

Hydrogen bond thermotropic ferroelectric liquid crystal of DL-tartaric acid and 4-heptyloxybenzoic acid (1:1): Experimental and density functional theory (DFT) approach

The current research work incorporates structural, experimental and computational studies of a hydrogen bond thermotropic ferroelectric liquid crystal (HBTFLC) complex synthesised from DL-tartaric acid (DLTA) and 4-heptyloxybenzoic acid (7OBA) with 1:1 ratio. Spectroscopic studies (XRD, NMR, FTIR, UV–Vis) and Density Functional Theory (DFT) are utilized to confirm intermolecular hydrogen bonds in the synthesised complex. Polarizing Optical Microscope (POM) study confirms the phase sequence (N*, Sm C*, Sm F* and Sm G*) while Differential Scanning Calorimetry (DSC) explore the thermal properties of the mesophases. The Frontier Molecular Orbital (FMO) and Molecular Electrostatic Potential (MEP) surface analysis also explore the donor-acceptor interactions, stability and chemical reactivity of the complex. The nature of H-bond is estimated by Natural Bond Orbital (NBO) studies with the support of Atom-in-Molecules (AIM) and Reduced Density Gradient (RDG) analysis. Nonlinear Optical (NLO) properties of the complex are studied by calculating its polarizability and hyperpolarizability.

Battling hazardous gas molecules with kekulene surfaces: A computational study

A Density Functional Theory were used to investigate the interactions between kekulene and various noxious gases, including methane(CH4), carbon dioxide (CO2), hydrogen(H2), ammonia(NH3), and sulfur dioxide(SO2). The adsorption energies and bond distances were computed, indicating successful molecular interactions with kekulene, particularly notable in the exothermic nature of the adsorption process. Enthalpy calculations further confirmed the exothermic nature of the reactions, suggesting spontaneous adsorption. The analysis of frontier molecular orbitals revealed distinctive electronic characteristics, with HOMO-LUMO plots indicating a significant energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). Chemical descriptors derived from these calculations provided insights into the reactivity and polarizability of the compounds. Furthermore, the molecular electrostatic potential (MEP) surface maps illustrated the electrostatic potential distribution, aiding in predicting the molecule’s reactivity. Overall, the study highlights the potential of kekulene as a selective adsorbent for toxic gas (SO2), offering valuable insights into its chemical and electronic properties for various applications, particularly in environmental and industrial settings.

Synthesis, spectral, DFT, topology, NCI and molecular docking studies of (1E,1′E)-N, N'-(sulfonylbis(4,1-phenylene))bis(1-(4-bromophenyl)methanimine)

The present study investigated the synthesis, structural, topological, and electronic properties of (1E,1′E)-N,N'-(sulfonylbis(4,1-phenylene))bis(1-(4-bromophenyl)methanimine) D4BR as well as its geometrical properties as well as its wave functional properties. Additionally, we examined the geometrical and wave functional properties of D4BR. The band gap values were calculated by using the density functional theory (DFT) approach. The reactive sites were determined through the utilization of molecular electrostatic potential (MEP) analysis. The calculation of excited energies (UV–Visible) was done by using the time dependant density functional theory (TD-DFT) approach and compared to the experimental UV spectral analysis. The natural bond orbital analysis (NBO) approach was employed to investigate the charge transfer, within the molecule by examining both intra-molecular and inter-molecular interactions. The highest dipole moment and hyper-polarizability values of the compound were identified by the investigation conducted by the non-linear optical (NLO) research. The molecular docking study identified the biological activity of the titled compound.

New halo-enaminones as potential CNS drugs: Synthesis, characterization, DFT, NLO, molecular docking, and ADMET analysis

Some new halo-enaminones (2b-2g) of (Z)-1-(((2-acetylphenyl)amino)methylene)naphthalen-2(1H)-one (2a) were successfully synthesized in a very good yield. They were characterized by spectroscopic techniques. The single crystal XRD analysis confirmed the structure, stereochemistry, and hydrogen bond interactions of the synthesized enaminones. Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) were employed to study theoretical attributes such as Structural analysis, Natural Bond Order analysis (NBO), Frontier molecular Orbital Analysis (FMO), Global and local reactivity descriptors, Molecular Electrostatic Potential (MEP) analysis, Absorption, Emission and Non-Linear Optical (NLO) properties. Molecular docking analysis revealed that all these compounds had an excellent binding energy of ∼ -12 kcal/mol, with the human Sirtuin 2 (SIRT2) protein (PDB ID: 5Y5N), which is predominantly expressed in the brain. In addition, ADMET analysis revealed that all of them have drug-like properties, Blood Brain Barrier (BBB) permeable, and are not P–Glycoprotein substrates, implying that they are potential Central Nervous System (CNS) drugs.

Theoretical study on different substituent-modified derivatives of 6-dinitrophenyl-5,6,7,8-tetrahydro-4-imidazo [4,5-e]furazano[3,4-b] pyrazine.

The compounds of the "565" parent ring structure have received much attention from researchers because of their excellent detonation performance. In the present study, 81 derivatives were designed by introducing different substituents based on 6-dinitrophenyl-5,6,7,8-tetrahydro-4-imidazo[4,5-e]furazano[3,4-b] pyrazine (DIOP), which is a compound of the parent ring structure of 565, and the performance of these derivatives, such as the electronic structure, energy gap, heat of formation, and detonation performance, were investigated. Among these energy-containing derivatives, the density ranges from 1.70 to 2.17g/cm3, the detonation velocity ranges from 8.01 to 10.26km/s, and the detonation pressure ranges from 27.99 to 49.88 GPa. Through comprehensive analysis of several properties of DIOP derivatives, it was found that the oxygen balance of derivatives with the -ONO2 group was greater than zero and close to zero, while the oxygen balance of derivatives with other groups was almost all less than zero. Among them, G8 (D = 10.1km/s, P = 47.72 GPa), H8 (D = 10.11km/s, P = 47.92 GPa), and I8 (D = 10.26km/s, P = 49.88 GPa) had higher detonation velocity and pressure among all derivatives, and their impact sensitivity was better than RDX. Therefore, three potential high-energy and less sensitive energy-containing derivatives, G8, H8, and I8, were screened out. The intramolecular interactions of the three derivatives were further analyzed, and it was found that there were intensive van der Waals interactions and significant spatial steric effects within the molecules, which had a positive effect on reducing the shock sensitivity of the compounds. Moreover, the three derivatives have a large degree of stacking, which leads to a high density. All calculations in this paper are performed using Gaussian16 based on density functional theory. Firstly, the structures of the derivatives were optimized at the level of B3LYP-D3/6-311G**, and then single-site energy calculations were carried out at the level of M06-2X-D3/def2-TZVPP, to reveal the effects of single substituents versus multiple substituents and isomerism on the properties of the DIOP-based energetic derivatives. Multiwfn was used to plot the density of states (DOS) of the derivatives and to calculate the molecular surface electrostatic potential at 0.001 e/Bohr3 electron density, 0.25 Bohr lattice spacing surface.