Frontier Molecular Orbital Analysis Research Articles

Structural and electronic assessments of Thiamazole adsorption on the transition metal doped fullerenes as a potential smart drug delivery platform

Adsorption of Thiamazole (TZOL, a medication to treat hyperthyroidism) on the transition metal (TM) doped fullerenes (MF) is investigated to gain insight into the potential development of a smart drug delivery platform. In this computational study, molecular models of adsorbed TZOL on TM-doped and undoped fullerenes were optimized and their structural and electronic features were evaluated using density functional theory (DFT) and the quantum theory of atoms in molecules (QTAIM). The TM-doped models were created by substituting a carbon atom of the original fullerene (F) with a metal atom of the first row of transition metals, yielding ten different MF models. TZOL adsorbate (TZOL@MF) showed stronger interaction through its sulphur group binding to the doped metal in comparison to the original carbon fullerene, i.e. TZOL@F. Our calculations indicate that the most stable conjugate system was TZOL on the vanadium-doped fullerene (TZOL@VF) with a free energy of −37.78 kcal/mol followed by Mn-doped fullerene (−36.86 kcal/mol) while that of all undoped fullerene is −9.18 kcal/mol. The impact of water on the stability of TZOL@MFs was investigated and results show that aqueous phases are even more stable than the gaseous phase, again, with TZOL@VF being the most stable of the conjugate adsorbate/adsorbent pair. Frontier molecular orbital analysis showed significant changes of electronic environment from the MF adsorbent to the TZOL@MF conjugated models. HOMO and LUMO levels and their gap energy detected the variations of electronic environment upon adsorption of TZOL, making this system a potential drug delivery platform capable of detection of loaded and released drug molecules.

Effect of TX-100 on solubilizing power of CTAB and CPC for H Acid: An experimental and computational analysis

The present research work investigates the solubility of an anionic dye 8-amino-1-naphthol-3,6-disulfonic acid (H Acid) within the micellar mediaof two cationic surfactants cetylpyridinium chloride (CPC) and cetyltrimethylammonium bromide (CTAB) as well as in the mixed micellar mediaof each cationic surfactant with Triton X-100 (TX-100). The data from differential absorption spectroscopy across a concentration range spanning from pre-micellar to post-micellar regions was used to determine the degree of solubilization by calculating the partition coefficient (Kx), binding constant (Kb) and Gibbs free energy associated with the relevant processes. Electrical conductivity of each cationic surfactant in the presence of H Acid was recorded in aqueous media and used to determine the CMC and subsequent thermodynamic parameters including entropy (ΔSm), enthalpy (ΔHm) and Gibbs free energy change (ΔGm) associated with the process of micellization. The computational analysis was carried out with GAUSSIAN 09 using a 6-311G + basis set with a DFT/ B3LYP hybrid approach and each set of energy minimization was executed to perform frequency calculations for Frontier molecular orbital analysis and to evaluate absorption spectra. Moreover, the molecular electrostatic potential surfaces (MESP) were also computed to find their suitable hydrophobic and hydrophilic interactions.

Biphenyl based schiff base derivatives of 6-aminocoumarin: Design, synthesis, mesomorphic properties and DFT studies

The study focused on synthesizing two series of coumarin Schiff base liquid crystals. These series involved molecules with variations in alkoxy chains at aldehyde ends: one being the Schiff base with 4′‑hydroxy-[1,1′]-biphenyl-4-carbaldehyde (ASBP series) and the other being alkyl 4-formyl-[1,1′]-biphenyl-4-carboxylate (AEBP series). The compounds were characterized using FTIR, NMR, and Mass spectral analyses. All the compounds were studied for their mesomorphic properties, differential scanning calorimetry (DSC) and polarized optical microscopy (POM). In both the homologous series, variation of alkyl chain length showed intriguing phase transitions. In the first homologous series ASBP, compound with hexyloxy chain displayed an enantiotropic nematic (N) phase, while those with chain lengths n = 8–16 exhibited enantiotropic smectic A (SmA) mesophase. Similarly, in the AEBP series, compounds with n = 6,8 chain length showed an enantiotropic nematic (N) phase, while those with higher chain lengths n = 10–16 exhibited enantiotropic smectic A (SmA) phases. SmA mesophase was further confirmed by powdered XRD analysis. The study included DFT theoretical calculations to comprehend the compounds' mesomorphic behavior, comparing them with analogous reported compounds. Additionally, the investigation correlated experimental findings of individual compounds with calculated parameters like polarizability, dipole moment, and aspect ratio. Molecular electrostatic potential projections and analysis of frontier molecular orbitals were also employed to elucidate how polarity variations in terminal chains and mesogenic cores influenced the energy gap of FMOs and the distribution of electrostatic charges on these compounds. It has been found that the ASBP series has lower energy gap and higher dipole moment than the AEBP series.

Density Functional Theory Calculations on Fluorescence-Enhanced Mechanisms of the Optical Sensor for Zinc Ions, ADPA.

N-(9-anthracenylmethyl)-N-(2-pyridinylmethyl)-2-pyridinemethanamine (ADPA) as a specific ion sensor for Zn2+ has been widely applied. Although the photo-induced electron transfer (PET) mechanism was proposed previously, its fluorescence-enhanced effect still remains somewhat ambiguous, according to unknown influences of non-radiative energy decay pathways, such as intersystem crossing and internal conversion. Herein, a thorough study using density functional theory has been performed for low-lying electronic states of the ADPA monomer and hydrated ADPA-Zn2+ complex. Based on interfragment charge transfer analyses, we quantitatively calculated the amount of transferred electrons in the monomer and complex, providing solid evidences for the PET mechanism and in line with the conclusion of frontier molecular orbital analyses. Moreover, the ISC process of S1→T2 was confirmed to play a considerable role in the excitation energy relaxation process of the ADPA monomer, but this influence was significantly suppressed in the hydrated ADPA-Zn2+ complex. These results provide additional clues for the design of new metal ion-specific fluorescence probes.

Synthesis, Crystal Structure, Computational Investigation of Vanillin Azine Derivative as Potent Blocker of the N‐Terminal Ras‐Binding Domain (RBD) in Human a‐Raf Kinase

AbstractVanillin is the main component of natural vanilla extract and is responsible for its flavoring properties. Besides its well‐known applications as an additive in food and cosmetics. In this, we have synthesized a new vanillin derivative. Its structure was characterized by IR, MS, NMR and confirmed by single‐crystal X‐ray analysis. The asymmetric unit of the title molecule consists of two independent half molecules, each having crystallographically imposed centrosymmetry. Reticular layers approximately parallel to the bc plane are generated from one molecule through O−H⋅⋅⋅N hydrogen bonds. The layers are linked by the second molecule through O−H⋅⋅⋅O hydrogen bonds to form a 3‐D network structure. We carried out density functional investigations to understand the compound‘s molecular reactivity and chemical stability. Frontier molecular orbital (FMO) analysis, global reactivity, and Fukui parameters were calculated at the B3LYP/6‐31+G(d,p) method. In 20 % to 30 % of human malignancies, RAS genes are activated ontogenetically by point mutations. New strategies to block this oncogenic protein are needed since it has proven difficult to create efficient RAS inhibitors. The above‐titled compound shows better structural activity relationship studies against Ras‐binding domine, based on this molecular docking simulation as well as the drug‐likeness analysis carried out for our newly synthesized compound.

In silico anticancer activity of isoxazolidine and isoxazolines derivatives: DFT study, ADMET prediction, and molecular docking

This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, employing a multifaceted approach that integrates Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Utilizing DFT analysis with the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, molecular geometries were optimized, and vibrational frequencies in the IR spectrum were evaluated, offering insights into the molecular structure and stability of the pharmaceutical compounds. Electrostatic potential maps were analyzed to predict functional group reactivity and protein-substrate interactions. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b exhibiting slightly higher stability. Chemical potential and hardness analyses highlighted stronger binding affinity for compounds 1b and 2b, suggesting stronger potential interactions. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, with compound 3b showing superior oral effectiveness. Molecular docking and dynamics simulations were conducted targeting the receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, which exhibited the most favorable binding energy of -8.50 kcal/mol. Molecular dynamics simulations demonstrated the superior stability of ligand 3b over 1b and 5-FU over 100 ns, suggesting its potential for further study. The 3b-protein complex exhibited stability through hydrophobic and hydrogen bond interactions, with 3b demonstrating reduced solvent exposure compared to 1b and 5-FU. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Synthesis, crystal structure, DFT calculations, NBO, Fukui function, NCI-RDG, Hirshfeld surface analysis, NLO properties and molecular docking analysis on (E)-N'-(3-methoxybenzylidene)-2-(quinolin-8-yloxy) acetohydrazide

In this study, we present the synthesis and characterization of a novel organic compound, (E)-N'-(3-methoxybenzylidene)-2-(quinolin-8-yloxy) acetohydrazide. Our characterization includes single crystal X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and UV–visible spectroscopy. We also conducted Hirshfeld surface (HS) analysis to investigate intermolecular interactions. The compound crystallizes in the triclinic system with space group P−1. We employed density functional theory (DFT) with the B3LYP function and the 6–311 G (d, p) basis set to calculate its electronic properties. Additionally, we explored its nonlinear optical (NLO) behavior, determining the electric dipole moment (μ), polarizability (α), and hyperpolarizability (β), second-order hyperpolarizabilities (γ) using the same basis set. To evaluate the NLO properties of MBQA, we conducted frontier molecular orbitals (FMO) analysis, examined HOMO-LUMO energies, determined the energy band gap, studied the density of states (DOS), and assessed global chemical reactivity descriptors. We also performed a molecular electrostatic potential (MEP) simulation to identify optimal sites for both electrophilic and nucleophilic attacks. Our analysis further included a reduced density gradient (RDG) analysis to investigate various types of intermolecular interactions in MBQA, such as repulsive, attractive, and Van der Waals interactions while also distinguishing between strong and weak interactions. To understand the molecular stability and interactions, we conducted natural bond orbital (NBO) analysis, which provided insights into hyperconjugative interactions, charge delocalization and electron density ED among the molecular components. Finally, we assessed the biological activity of the MBQA molecule by predicting its potential pharmacological activities using the prediction of activity spectra for substances (PASS) and conducting molecular docking analyses. This comprehensive study provides valuable insights into the structural, electronic, and biological properties of (E)-N'-(3-methoxybenzylidene)-2-(quinolin-8-yloxy) acetohydrazide (MBQA).

Nonlinear optical properties of azo sulfonamide derivatives.

The present work deals with the linear and nonlinear optical properties such as the dipole moment, polarizability, total hyperpolarizability, electric field-induced second harmonic generation, and hyper-Rayleigh scattering first hyperpolarizability of four heterocyclic azo compounds containing the sulfonamide group considered promise in nonlinear optic. The obtained polarizability and hyperpolarizability were supported by the frontier molecular orbital analysis. The properties have been effectively estimated and thoroughly examined to shed light on the nonlinear optical activity based on the density functional theory. The observed results show a high total first hyperpolarizability up to 2503 a.u. and a low energy gap less than 1.41 eV. An inverse relationship has been obtained between the and . The calculated values confirm that charge occurs within the azo sulfonamides. The new study provides a promising avenue for the development of these azo sulfonamides as novel NLO materials. The molecular modeling and the theoretical studies were performed with Gaussian software packages. The B3LYP/6-311 + G** level was used for optimization. All the linear and nonlinear optical properties reported here are obtained using the DFT. The optimized structures and their frontier molecular orbitals were plotted using the GaussView 5.1 program.

Crystal structure, molecular mechanics and In silico analyses of piperizine derivative against human mammary carcinoma cells inhibition.

In the present study, the single crystal of novel piperazine derivative4-(2, 3-chlorophenyl) piperazine-1-yl) (2-hydroxyphenyl) methanone (KDM) is grown by using the solvent evaporation method. The 3D structure of the molecule is confirmed by the single-crystal X-ray diffraction method. The study revealed that the molecular system is crystallized in the orthorhombic system with space group Pbca . The supramolecular crystal architecture establishes the stability of a compound via short contacts and halogen-hydrogen interactions. The Hirshfeld surface analysis were performed to evaluate the numerous intermolecular interactions based on the anisotropy of the topology. The Frontier molecular orbital (FMO) analysis and Molecular electrostatic potential (MEP) plots are investigated to understand the electronic structure properties of compounds using Density Functional Theory (DFT). In silico molecular docking, analysis is carried out to predict the best binding pose of the compound in the active site pocket of the BCl-XL/BAK protein-protein interface. Further, in vitro cytotoxicity studies against human breast cancer (MCF-7) cell lines of similarly designed piperazine-based derivatives showed prominent results. The results of the current study revealed that the compounds under investigation possess potential anti-cancer properties.

TDDFT Study on the ESIPT Properties of 2-(2'-Hydroxyphenyl)-Benzothiazole and Sensing Mechanism of a Derived Fluorescent Probe for Fluoride Ion.

The level of fluoride ions (F-) in the human body is closely related to various pathological and physiological states, and the rapid detection of F- is important for studying physiological processes and the early diagnosis of diseases. In this study, the detailed sensing mechanism of a novel high-efficiency probe (PBT) based on 2-(2'-hydroxyphenyl)-benzothiazole derivatives towards F- has been fully investigated based on density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods. F- attacks the O-P bond of PBT to cleavage the dimethylphosphinothionyl group, and the potential products were evaluated by Gibbs free energy and spectroscopic analyses, which ultimately identified the product as HBT-Enol1 with an intramolecular hydrogen bond. Bond parameters, infrared vibrational spectroscopy and charge analysis indicate that the hydrogen bond is enhanced at the excited state (S1), favoring excited state intramolecular proton transfer (ESIPT). The mild energy barrier further evidences the occurrence of ESIPT. Combined with frontier molecular orbital (FMO) analysis, the fluorescence quenching of PBT was attributed to the photoinduced electron transfer (PET) mechanism and the fluorescence turn-on mechanism of the product was attributed to the ESIPT process of HBT-Enol1.

Investigating the impact of solvation on p-Phenylenediamine - 2-Amino pyrimidine - Formaldehyde Terpolymer (P2APF) ligand's reactivity and drug suitability for malaria treatment: Insights from experimental and quantum calculations

This study aims at investigating the drug potential of p-Phenylenediamine – 2-Amino Pyrimidine – Formaldehyde terpolymer (P2APF) ligand against drug resistant Plasmodium falciparum. Plasmodium falciparum, an embodiment of cunning among malaria parasites, thrives in regions plagued by rampant mosquito transmission, subpar vector control, and limited access to effective treatments. To this end, this study explored the structural properties of the p-Phenylenediamine – 2-Amino Pyrimidine – Formaldehyde terpolymer (P2APF) ligand, (comprising p-Phenylenediamine, 2-Aminopyrimidine, and Formaldehyde) as a drug potent ligand against the common proteins coding for malaria infection. Various spectroscopic techniques such as FT-IR, UV–visible, and NMR (1H & 13C) spectroscopy were employed both experimentally and theoretically. Additionally, the ligand's surface morphology was investigated using scanning electron microscopy. To comprehend the influence of solvation, theoretical investigations utilizing density functional theory (DFT) at the B3LYPD(BJ)/6-311G++G (2d,2p) level were conducted in DMSO, water, and methanol solvents. The results from the frontier molecular orbital (FMO) analysis provided valuable insights into the electronic properties and solvation effects of P2APF. Specifically, the calculated energy gap of 3.671 eV for P2APF_methanol and 3.672 eV for P2APF_DMSO suggested these solvents as promising environments for reactivity and interactions. Molecular docking studies unveiled the most notable binding affinity between P2APF and the 5UMB chaperone protein receptor, exhibiting a binding affinity of -7.3 kcal/mol on serine and aspartic acid residues, with an average bond distance of 2.25 Å. This robust protein-ligand interaction signifies the promising potential of the P2APF ligand in targeting this specific receptor, thereby combating drug-resistant strains of Plasmodium falciparum for the present and the future.

Improved the optical nonlinearity of carbazole based chromophores via molecular engineering: A DFT approach

The present investigation was based on designing of carbazole based derivatives (DTCFD1–DTCFD8) having D1-π-D2-π-A architecture from DTCFR, upon substituting acceptor motifs for nonlinear optical (NLO) materials. M06-2X/6-311G(d,p) level was accomplished to explore the optoelectronic behavior of designed compounds. The UV–Vis, density of states (DOS), natural bond orbitals (NBOs), transition density matrix (TDM) and frontier molecular orbitals (FMOs) analyses were executed to comprehend the nonlinear optical properties of above-mentioned compounds. The FMO analysis showed DTCFD7 as having the lowest energy gap at 3.734 eV among the derivatives, indicating its potential for efficient charge transfer. The overall decreasing order of band gaps was observed: DTCFR > DTCFD5 > DTCFD3 > DTCFD1 > DTCFD2 > DTCFD4 > DTCFD6 > DTCFD7. UV–Visible analysis exploited that DTCFD7 displayed distinctive absorption characteristics. In the gas phase, it exhibited a λmax of 494.927 nm, while in the dichloromethane it showed a significantly higher λmax of 516.515 nm, then all other derivatives. All the derivatives exhibited greater values of linear polarizability [〈α〉=1.633–1.786 × 10−22esu], first hyperpolarizability (βtot = 3.690–6.549 × 10−28esu) and second hyperpolarizability (γtot = 4.825–7.229 × 10−33esu) as compared to the reference molecule. Furthermore, NLO analysis revealed that the highest βtot (6.549 × 10−28esu) and γtot (7.229 × 10−33esu) was exhibited by DTCFD7 and DTCFD1, respectively, then other derivatives. Moreover, a comparative study with standard urea and para-nitroaniline (p-NA), exhibited effective NLO properties in current study compounds. In light of the comprehensive findings, this study concludes that the designed compounds may be considered as effective NLO materials.

Synthesis, crystal structure, Hirshfeld surface analysis, spectral characterisation, non-covalent interactions and anti-microbial investigation on morpholinium adipate: a combined experimental and DFT approach

MPAA was synthesised and evaluated using spectroscopic methods and quantum chemical computations in the proposed investigation. Extensive quantum chemical computations were employed to analyse FT-IR, FT-Raman and NMR spectra of molecule morpholinium adipate (MPAA). The results of a single crystal X-ray diffraction (SCXRD) experiment were compared with estimated structural characteristics. In conjunction with the scaled force constants, a comprehensive vibrational assignment is provided for the 96 anticipated vibration modes of MPAA. Charge transport inside the molecule is exposed by the band gap energy of 5.959 eV, which is the consequence of the predicted Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) values of −6.991 and −1.031 eV, respectively. The inter- and intramolecular H-bonding contacts in the molecule were studied using natural bond orbital analysis to learn more about the biological active site. The eventual charge transfer inside the molecule is supported by frontier molecular orbital analysis and natural bond orbital analysis. The anti-bonding of H15–O24 atoms and the lone pair N14 had the greatest stabilising energy at 16.52 kcal/mol. Using Hirshfeld surface analysis methods, intermolecular connections and crystal packing of MPAA are investigated. The fukui and electrostatic potential plot analyses can provide information about the molecule’s electrophilic and nucleophilic locations. Antimicrobial tests have been performed to see how well the chemical worked against various bacterial and fungal strains. Docking of 8OEO (Aspergillus Niger), 7C2O (Candida parapsilosis), 2O6I (Enterococcus faecalis) and 1DZO (Pseudomonas aeruginosa) proteins has been done, and lowest binding energy −4.57 kcal/mol has been achieved for 7C2O protein.

Synthesis, solvent role, absorption and emission studies of cytosine derivative

The (E)-4-((4-hydroxy-3-methoxy-5-nitrobenzylidene) amino) pyrimidin-2(1H)-one (C5NV) was synthesized from cytosine and 5-nitrovanilline by simple straightforward condensation reaction. The structural characteristics of the compound was determined and optimized by WB97XD/cc-pVDZ basis set. The vibrational frequencies were computed and subsequently compared to the experimental frequencies. We investiated the electronic properties of the synthesized compound in gas and solvent phases using the time-dependent density functional theory (TD-DFT) approach, and compared them to experimental values. The fluorescence study showed three different wavelengths indicating the nature of the optical material properties. Frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) analyses were conducted for the title compound, and electron localized functions (ELF) and localized orbital locators (LOL) were used to identify the orbital positions of localized and delocalized atoms. Non-covalent interactions (H-bond interactions) were investigated using reduced density gradients (RDGs). The objective of the study was to determine the physical, chemical, and biological properties of the C5NV. The molecular docking study was conducted between C5NV and 2XNF protein, its lowest binding energy score is −7.92 kcal/mol.

A theoretical approach to the corrosion inhibition of iron in acidic solution by a green formulation derived from Nigella sativa L seeds oil

A theoretical approach combining density functional theory (DFT) computation, Monte Carlo (MC) methods, and molecular dynamics (MD) simulations was used to investigate and validate the iron corrosion inhibition performances in the acidic medium of a green formulation based on the oil extracted from Nigella sativa L. DFT calculations allowed to determine the energetic, global, and local chemical reactivity parameters. The most stable adsorption configuration of the fatty acids components of the Nigella sativa L. formulation was determined by the Monte Carlo methods with the adsorption locator module and by molecular dynamics simulations. Results indicated that all the compounds are absorbed with a totally flat orientation on the first layer of the metal surface.The active sites of molecules were effectively established by using DFT through the analysis of frontier molecular orbitals (FMO), the Hirshfeld population analysis (HPA), the electrostatic potential (ESP), molecular electron density analysis (MED), and Fukui indices (FI). The solvent effect was investigated by using the conductor-like polarizable continuum model (CPCM). Protonation effects were also analysed through the protonation energy (PE), the proton affinity (PA), and the absolute gas phase basicity (GB). The formation of a coating on the iron surface validated the good protective action of the green formulation derived from Nigella sativa L.The computational and theoretical approaches substantiate our experimental electrochemical and spectroscopic studies [1].

Integrated insights into the structure, spectroscopy, and reactivity of a novel Brucinium Tetraphenylborate: A comprehensive computational and experimental study

The current study examines the crystal development and structure of a recently synthesized 2,3-dimethoxystrychnidin-10-one (brucine) tetraphenylborate, using both experimental and theoretical examinations. Brucinium tetraphenylborate crystal (1) was successfully synthesized and characterized using Single Crystal X-ray Diffraction. The crystal lattice is intricately defined by prevailing N/C-H···O hydrogen bonds and O/C-H···π interactions, establishing a cohesive molecular network. To elucidate intermolecular interactions within the crystal packing, Hirshfeld surface analysis and 2D fingerprint plots are employed. Validation of experimental findings is conducted through rigorous Density Functional Theory (DFT) calculations employing the B3LYP and CAM-B3LYP functionals, in conjunction with the 6–311+G* basis set. The reactivity profile of the title molecule is systematically explored through the analysis of frontier molecular orbitals (FMO), HOMO-LUMO energies, molecular electrostatic potential (MEP), and global chemical reactivity descriptors. Notably, computational insights reveal that the energy gap (Eg) and other chemical reactivity descriptors are intricately associated with both tetraphenylborate and brucine moieties. This emphasizes their pivotal roles in the overall activity and antioxidant capacity of the molecule. This research contributes to the understanding of the intricate molecular dynamics, shedding light on key factors influencing the compound's reactivity and potential antioxidant properties.

Cavitands based nanocapsule as smart and highly effective vehicle for 5-fluorouracil anti-cancer drug delivery: DFT insights

The nanomaterials have been widely investigated as drug delivery system for a variety of anticancer drugs to limit their adverse effects while transporting to the target site. In the current study, we report the cavitand-based nanocapsules as a drug delivery vehicle for nitrosourea (NU) and fluorouracil (FU) anti-cancer drugs. FU and NU drugs interact with the nanocapsules with the interaction energies in gas phase (solvent) −24.78 kcal/mol (–22.39 kcal/mol) and −21.58 kcal/mol (-20.45 kcal/mol), respectively. The results of Quantum theory of atoms in molecules (QTAIM) and noncovalent index (NCI) analyses indicate that the FU@Capsule and NU@Capsule complexes are mainly stabilized through hydrogen bonding and van der Waals interactions. Electron density difference (EDD) and natural bond order (NBO) analyses reveal that significant amount of charge is transferred from the nanocapsule to drug molecules. Frontier molecular orbital (FMO) analysis also reveals slight reduction in the energy gap. AIMDS analysis shows that cavitand capsules can efficiently carry the anti-cancerous drug to their target site without distorting complexes. The dipole moments and pH effect are studied to understand the drug release mechanism of considered anticancer drugs. The decrease in adsorption energy and increase in interaction distances indicate that anticancer drugs can easily be off-loaded from the carrier (nanocapsule) at the target site due to the low pH of cancerous cells compared to the normal cells. Therefore, cavitand nanocapsule can be employed as an excellent drug delivery carrier in smart targeted drug delivery.

Synthesis, crystal structure investigation and computational studies binding of (7S,8R)-7-acetyl-8-(4-chlorophenyl)-3-(ethylthio)-1,6-dimethyl-7,8-dihydroisoquinoline-4-carbonitrile with monoamine oxidase B

This work reports the preparation of a new dihydroisoquinoline derivative whose structure was characterized by IR, NMR (1H, 13C), MS and verified through single-crystal X-ray analysis. The mean planes of the acetyl and 4-chlorophenyl groups in the title molecule are nearly perpendicular to that of the pyridine ring. In the crystal, π-stacking and C—H···O hydrogen bond interactions involving the pyridine ring and the nitrile group of an adjacent molecule form the full 3-D structure. Hirshfeld surface (HS) analysis shows the topology of the molecules in the crystal packing. Fingerprint (FP) diagrams show the percentage contribution of several intermolecular interactions where H‧‧‧H interactions have a significant contribution (46%). The DFT study reveals a low HOMO-LUMO gap and significant charge transfer is indicated by the natural bonding orbitals (NBO) and frontier molecular orbital (FMO) analyses. Non-covalent interactions and bond characteristics were investigated using the quantum theory of atom in the molecule (QTAIM) and ELF analysis. FMO analysis was used to calculate the HOMO-LUMO energy gap and orbital energies. Using the DFT method, parameters such as global reactivity were calculated. Using the implicit solvent model, properties such as optical and nonlinear optical (NLO) were characterized in the solvent (water) phase and gas phase. The affinity of the title molecule for Monoamine Oxidase B was examined using molecular docking and molecular dynamics studies and these results showed good binding of the target molecule.

In silico evaluation of a new compound incorporating 4(3H)-quinazolinone and sulfonamide as a potential inhibitor of a human carbonic anhydrase

The present study investigates the potential of a new compound containing sulfonamide and 4(3H)-quinazolinone to inhibit the hCA-IIX enzyme using in silico methods. Density functional theory-based calculations of electronic properties have been addressed through the analysis of frontier molecular orbitals, molecule electrostatic potential, and IR and UV–vis spectroscopy data. A molecular electrostatic potential analysis predicts that the target protein will be most inhibited by the sulfonamide groups since it has the highest potential spots for electrophile and nucleophile attack. The investigated compound exhibited good ADMET properties and satisfied the Lipinski rule of drug likeness. The hCA-IIX protein binding affinity with the proposed compound was determined by molecular docking analysis, which revealed a stable conformation with more negative binding energy (−12.19 kcal/mol) than the standard AZA drug (−7.36 kcal/mol). Moreover, a molecular dynamics study confirmed the docking results through trajectory analysis. The RMSD and RMSF both showed convergence and no significant fluctuations during the simulation time, which revealed a stable interaction within the active domain of the target protein. According to these findings, the proposed compound has a good pharmacological nature and could potentially be an efficient drug against hCAIX enzymes.

Theoretical investigation on regulating photophysical properties and proton transfer behavior by electronegativity for near-infrared emitting styryl dyes.

Our main focus is to explore the atomic electronegativity-dependent photoinduced behavior of styryl derivatives (HBO, HBS, and HBSe). The results of structural parameter calculation by the DFT method show that the intramolecular hydrogen bonds of normal and tautomer form are strengthened and weakened, respectively, in an excited state (S1), which is conducive to the excited intramolecular proton transfer (ESIPT) process. The enhancement of excited hydrogen bond is beneficial to the ESIPT process from the aspects of infrared vibration frequency (IR), Mulliken's charge analysis, and density gradient reduction (RDG). Additionally, by determining the bond energy with the band critical point (BCP) parameter, we found that the lower the electronegativity of the atom, the larger the hydrogen bond strength at the excited state and the more likely ESIPT reaction occurs. Meanwhile, the intramolecular H-bonds O-H…N in HBO, HBS, and HBSe are enhanced with the weakened electron-withdrawing capacity of the atom (from O to S and Se). Subsequently, frontier molecular orbital (FMOs) and charge density difference (CDD) analyses essentially revealed that electron redistribution induces the ESIPT process. Low atomic electronegativity exhibits the high chemical activity of the excited state. Furthermore, to demonstrate the electronegativity-dependent ESIPT behavior of the system, we built potential energy curves (PECs) and located the transition states (TS) of proton transfer processes.