TD-DFT Method Research Articles

Synthesis, Urease Inhibitory Activity, Molecular Docking, Dynamics, MMGBSA and DFT Studies of Schiff Bases Bearing Benzimidazole Scaffold.

In this study, eleven hydrazone-Schiff bases bearing benzimidazole moiety were synthesized successfully via three step reactions and structures of these products were deduced by HR-ESI-MS, 1H-, and 13C-NMR spectroscopic techniques. Lastly, these derivatives were tested for their in vitro urease inhibitory potential. Six compounds among the series attributed excellent inhibition with IC50 values of 7.20 ± 0.59 to 19.61 ± 1.10 µM better than the reference drug thiourea (IC50 = 22.12 ± 1.20 µM). Similarly, three derivatives showed significant while two compounds showed less inhibitory effects against the urease enzyme. The molecular docking analysis was carried out to reveal the binding modes and types of interaction taking place between protein (urease) and synthesized compounds. The Density Functional Theory (DFT) calculations were performed at B3LYP/6-311++G(d,p) to check the structure stability. For the account of intramolecular interaction, the DFT-D3 and Reduced Density Gradient (RDG) analysis were performed. Furthermore, the chemical nature of all compounds was explored by TD-DFT method using CAM-B3LYP functional with 6-311++G(d,p) basis set. The dynamic simulation as well as MMGBSA studies validated the binding affinity and stability of the ligand receptor complex, displaying main interactions contributing in the biological activity of the product derivatives.

Spectroscopic, quantum computational, molecular dynamic simulations, and molecular docking investigation of the biologically important compound-2,6-diaminopyridine

To establish the role in future drug development, 2,6-diamino pyridine (2,6-DAP) was investigated experimentally using computational tools. NMR (1H,13C), FTIR, and UV–Vis spectra were analyzed for the titled compound. The molecular structure was optimized via DFT with the “B3LYP method with 6-311++G(d,p)” The optimized parameters of the structure were assessed with the observed bond characteristics. The vibrational frequencies were studied, PED was carried out, and the calculated vibrational frequency obtained was compared with the experimentally obtained FTIR. NMR (1H,13C) was calculated and compared with the experimentally obtained spectra. UV–vis spectra are calculated in the gaseous phase and different mediums of solvents (methanol, DMSO) by employing the PCM solvent model and TD-DFT method, and the estimated value was compared with experimentally measured data. NBO analysis was done to study the donor-acceptor interaction. The extent of electron charge transfer inside the molecular structure was examined using HOMO–LUMO energy values. The study of excitation analysis led to the creation of E.D.D and H.D.D maps in methanol and DMSO. The AIM and ELF analysis was employed to compute the iso-surface projections, ellipticity, and binding energies. The MEP and Fukui functions evaluate the molecule’s reactive zones. Hirshfeld research was done to analyze interactions among the molecules in the structure of the crystal, and 3D Hirshfeld tops and 2D fingerprint layouts were developed. The molecular docking procedure was used, followed by a 100 ns MD simulation and computation of binding free energy found to delineate the binding affinity of the molecule toward human carbonic anhydrase II (HCA II). Molecular docking studies with several receptor proteins were also conducted to determine the most effective protein-ligand interactions. Biological assessments like drug-likeness also act upon the compound to verify the molecule’s drug-like nature.

Molecular designing and structural tuning of derivatives of 4,7-divinyl-1H-benzo[b]silole for optoelectronic properties using DFT and TD-DFT methods

Molecular designing and structural tuning of derivatives of 4,7-divinyl-1H-benzo[b]silole for optoelectronic properties using DFT and TD-DFT methods

Computational Insight into the Optoelectronic and Chemical Reactivity Properties of Metal-Free Phenothiazine Based D-π-A Dye-Sensitizers for Solar Cells Application: DFT and TD-DFT Methods

Computational Insight into the Optoelectronic and Chemical Reactivity Properties of Metal-Free Phenothiazine Based D-π-A Dye-Sensitizers for Solar Cells Application: DFT and TD-DFT Methods

Unveiling the Redox Noninnocence of Metallocorroles: Exploring K-Edge X-ray Absorption Near-Edge Spectroscopy with a Multiconfigurational Wave Function Approach.

X-ray absorption near-edge spectroscopy (XANES) is an advanced technique for probing the local electronic structure of catalysts, effectively identifying the noninnocent nature of ligands in transition-metal complexes. Metallocorroles with noninnocent corrole rings exhibit unusual electronic structures that challenge traditional density functional theory (DFT) methods, necessitating more rigorous approaches to describe electron correlation accurately. We explored K-edge XANES spectra of Fe, Mn, and Co metallocorroles using TDDFT and wave function-based methods. This is the first investigation employing multireference methods, specifically RASSCF, RASPT2, and MC-PDFT, to analyze the redox noninnocent nature of metallocorroles reflected in their XANES spectra. We quantified the noninnocent character of the corrole and the oxidation states of the metals, capturing more than singly excited excitations responsible for the pre-edge peak. Our findings demonstrate the importance of these advanced computational techniques for accurately predicting XANES spectra, providing a reliable understanding of the electronic properties of such complexes. This study offers a new strategy for investigating ligand redox noninnocence via integrated experimental and computational XANES.

Optimal donor groups for novel organic dye “3-(5-(4-(diphenylamino)styryl)thiophen-2-yl)-2-cyanoacrylic acid” in the context of N‑type dye-sensitized solar cells: A theoretical investigation

Theoretical modeling using DFT and TDDFT methods explored optimal donor groups for the organic dye “3-(5-(4-(Diphenylamino)styryl)thiophen-2-yl)-2-cyanoacrylic Acid”. Seven different moieties and their derivatives mostly used as donors as obtained from the literature (methylamine, benzene, fluorene, carbazole, phenylaniline, indolizine and pyrrolizine) were investigated, and our calculations highlighted indolizine and pyrrolizine derivatives as the most effective donors among those studied. The strong push pull effect of such derivatives of indolizine and pyrrolizine groups played a role in enhancing the efficiency of the dye sensitizers.

Synthesis, structural characterization and computational studies of half- sandwich Ru(II) (η6-p–cymene) TPA appended benzhydrazone complex

A ruthenium complex of the type Ru[η6(p–cymene)Cl(L)] where L = Triphenylamine (TPA) appended O^N bidendate benzhydrazone ligand was synthesized and characterized by various analytical and spectral [UV, FT-IR, NMR (1H and 13C) and HRMS] methods. The solid state molecular structure of the ruthenium complex was investigated with the aid of X-ray crystallography results with pseudo-octahedral geometry around the metal centre. FT-IR spectroscopy confirms the coordination via the azomethine nitrogen and imidolate oxygen. Density Functional theory (DFT) calculations have been used to analyse the composition of frontiers orbitals. The bonding interactions between the ligand and ruthenium complex fragments have been examined by EDA. The spin-allowed singlet transitions were calculated with the TD-DFT method. NBO analysis shows that the donation from ligand to metal has value of 136.64 kcal/mol and the back donation is equal to 109.61 kcal/mol. Hence the ligand is a σ-donor with weak π-acceptor properties. The DOS spectrum of both ligand and complex were plotted in terms of Mullikan population analysis were calculated using the GassSum program. Further, the relative contributions to the Hirshfeld surface area for the various close intermolecular contacts of ruthenium complex are investigated and H…H interactions plays an important role for the construction of the crystal structure of the ruthenium complex.

Bis-chalcones obtained via one-pot synthesis as the anti-neurodegenerative agents and their effect on the HT-22 cell line

In the area of research on neurodegenerative diseases, the current challenge is to search for appropriate research methods that would detect these diseases at the earliest possible stage, but also new active structures that would reduce the rate of the disease progression and minimize the intensity of their symptoms experienced by the patient. The chalcones are considered in the context of candidates for new drugs dedicated to the fight against neurodegenerative diseases. The synthesis of bis-chalcone derivatives (3a-3d), as aim molecules was performed. Their structures were established by applying 1H NMR, 13C NMR, MS, FT-IR and UV–Vis spectra. All bis-chalcones were synthesized from terephthalaldehyde and appropriate aromatic ketone as substrates in the Claisen-Schmidt condensation method and evaluated in the biological tests and in silico analysis. Compounds exerted antioxidant activity using the HORAC method (3a-3d) and decreased the activities of GPx, COX-2 (3b-3d), GR (3a-3c) and CAT (3a,3b). The high anti-neurodegenerative potential of all four bis-chalcones was observed by inhibition of acetyl- (AChE) and butyrylcholinesterase (BChE) and a positive effect on the mouse hippocampal neuronal HT-22 cell line (LDH release and PGC-1α, PPARγ and GAPDH protein expression). TD-DFT method (computing a number of descriptors associated with HOMO–LUMO electron transition: electronegativity, chemical hardness and potential, first ionization potential, electron affinity) was employed to study the spectroscopic properties. This method showed that the first excited state of compounds was consistent with their maximum absorption in the computed UV–Vis spectra, which showed good agreement with the experimental spectrum using PBE1PBE functional. Using in silico approach, interactions of bis-chalcones with selected targets (aryl hydrocarbon receptor (AhR) PAS-A Domain, ligand binding domain of human PPAR-γ, soman-aged human BChE-butyrylthiocholine complex, Torpedo californica AChE:N-piperidinopropyl-galanthamine complex and the COX-2-celecoxib complex) were characterized. Results obtained in in silico models were consistent with in vitro experiments.

Uncovering solvent-polarity-associated excited state behaviors for the novel PQ-BSD fluorophore: A theoretical study

In view of the prominent regulated characteristics of electron-donating substituted julolidine-bis(salicylidene)-1,5-diaminonaphthalene (PQ-BSD) derivatives, we are dedicated to exploring photo-induced excited state behaviors of PQ-BSD in solvents. Given the variational solvent polarities, the geometrical changes, infrared (IR) spectral variations, core-valence bifurcation (CVB) indexes as well as charge reorganizations are focused on based on TDDFT method. The strengthened excited-state hydrogen bonding interactions of both hydrogen bonds fully present the excited state intramolecular proton transfer (ESIPT) tendency. Via constructing potential energy surfaces (PESs), the stepwise excited state intramolecular double proton transfer (ESIDPT) process could be revealed for PQ-BSD fluorophore.

Structural, electronic, and NLO properties of two acridone alkaloîds: DFT and TD-DFT studies.

The structural, electronic, and nonlinear optical properties of Verdoocridone A (Ver A) and B (Ver B) are examined theoretically in this study. The results showed that Ver A and B exhibit good electronic properties and can be used as new materials in NLO applications. According to their maximum absorption wavelength, Ver A (λmax = 313nm) enables production of vitamin D, while Ver B (λmax = 319.55nm) can help skin pigmentation. All calculations were performed at the DFT/B3LYP-D3/6-311 + G(d,p) level of theory using the Gaussian 16 software package. Excited states were simulated using the TD-DFT method at the CAM-B3LYP combined with 6-311 + (d,p) basis set. Also, the solvent effect was studied in water and benzene phases by the solvation model based on density (SMD) method.

Effect of methyl trifluoride substitution on colorless transparency of polyimide: A DFT/TD-DFT study

The rapid advancement of flexible electronic devices has rendered high-performance colorless transparency polyimide (PI) films essential for energy storage and devices. However, there still remains controversy regarding the charge-transfer complexes in relation to the optical properties of PIs. Herein, we employed a combination of DFT and TD-DFT methods to elucidate the hole and electron characteristics of PIs. The results revealed that the incorporation of a CF3 group significantly enhances the dipole moment. Notably, the incorporation of CF3 groups onto both the anhydride and diamine units impedes charge transfer, resulting in a reduction of the HOMO energy level and an increse of the LUMO energy. The calculation results also indicate that the introduction of CF3 groups markedly hinders charge transfer within P4 in its excited state, leading to the minimum values for three characteristic parameters (D = 2.60 Å, CT = 0.51 e, t = 0.53 Å). Therefore, P4 exhibits a shortest charge transfer pathway resulting in minimal electron transfer and obvious blue-shifted UV–vis spectra, thus contributing to its excellent colorless transparency. This work provides a theoretical foundation and guidance for targeted design and development of colorless transparent PI films.

Synthesis, structural analysis, and molecular docking of a novel 1,3,4-thiadiazole derivative: An experimental and molecular modeling studies

This study reports on the synthesis and characterization of a new thiadiazole derivative, (E)-N-(5-(2-nitrostyryl) -4-acetyl -4,5-dihydro -1,3,4-thiadiazol -2-yl) -N-phenylacetamide (ETDZ). The crystal structure was determined by single-crystal X-ray diffraction. ETDZ belongs to the monoclinic I2/a space group. The contribution of intermolecular interactions was assessed by Hirshfeld surface analysis and fingerprint plots. FT-IR, UV–Vis, and NMR (1H and 13C) techniques were used for spectroscopic characterization. The 1H and 13C NMR spectra were recorded in CDCl3 solvent. Density functional theory, employing the B3LYP functional and 6–311G(d,p) basis set in chloroform solvent, was used to calculate the structural and spectroscopic parameters of the molecule in the ground state. The vibrational wavenumbers were calculated and compared with the experimental FT-IR spectrum using the scaled quantum mechanics method. Isotropic chemical shifts were calculated using the Gauge invariant atomic orbital method. The calculated NMR chemical shifts and absorption wavelengths were compared with the experimental values, indicating good results from the DFT and TD-DFT methods. To get more information about charge transfer within the molecule, electronic properties such as HOMO and LUMO energies were studied using the DFT approach. The molecular electrostatic potential, frontier molecular orbital analysis, energy band gap, density of state, global chemical reactivity descriptors, and some thermodynamic functions were also calculated. Reduced density gradient and atom-in-molecule analysis were performed to investigate inter- and intra-non-covalent interactions. Molecular docking was carried out with the Eg5 kinesin protein, confirming the biological assets of the ETDZ ligand as a mitochondria disease and cancer agent.

Core Hole Effect to Valence Excitations: Tracking and Visualizing the Same Excitation in XPS Shake-Up Satellites and UV Absorption Spectra.

Introducing a core hole significantly alters the electronic structure of a molecule, and various X-ray spectroscopy techniques are available for probing the valence electronic structure in the presence of a core hole. In this study, we visually demonstrate the influence of a core hole on valence excitations by computing the ultraviolet absorption spectra and the shake-up satellites in X-ray photoelectron spectra for pyrrole, furan, and thiophene, as complemented by the natural transition orbital (NTO) analysis over transitions with and without a core hole. Employing equivalent core hole time-dependent density functional theory (ECH-TDDFT) and TDDFT methods, we achieved balanced accuracy in both spectra for reliable comparative analysis. We tracked the same involved valence transition in both spectra, offering a vivid illustration of the core hole effect via the change in corresponding particle NTOs introduced by a 1s core hole on a Cα, Cβ, or O atom. Our analysis deepens the understanding of the core hole effect on valence transitions, a phenomenon ubiquitously observed in general X-ray spectroscopic analyses.

Alliaceumolide A: A rare undescribed 17-membered macrolide from Indonesian Dysoxylum alliaceum

Alliaceumolide A (1), a new macrolide together with known ivorenolide B (2) were isolated from Dysoxylum alliaceum (Blume) Blume ex A.Juss. These compounds were classified as 17-membered macrolide, which is a rare structure for plant-derived natural products. The structures were elucidated by extensive spectroscopic analyses, and the absolute configuration of 1 was determined by electronic circular dichroism (ECD) using TDDFT method. Furthermore, compounds 1 and 2 were tested for cytotoxic activity against two cancer MCF-7 and HeLa cell lines.

Interdisciplinary insights into (1′R,3S,3′R)-1'-(4-chlorobenzoyl)-5′,6′,7′,7a′-tetrahydro-1′H dispiro[indoline-3,2′-pyrrolizine-3′,3″-indoline]-2,2″-dione: Structural, electronic, and molecular dynamics perspectives

In the field of heterocyclic compounds, the spiro-pyrrolidine and oxindole ring systems are highly esteemed due to their distinctive structural scaffold that is present in numerous pharmacologically significant alkaloids. Interdisciplinary research has been increasingly important in recent years for deciphering the intricate characteristics and behaviors of novel organic compounds. The current work uses quantum chemical computational techniques to study the structural stability and nonlinear optical (NLO) activity of (1′R,3S,3′R)-1'-(4-chlorobenzoyl)-5′,6′,7′,7a′-tetrahydro-1′H dispiro[indoline-3,2′-pyrrolizine-3′,3″-indoline]-2,2″-dione (DSOIP-Cl). The study combines molecular biology, computational chemistry, and theoretical chemistry knowledge to create a comprehensive picture of this fascinating organic compound. This study employed the density functional theory (DFT) B3LYP method to compute the electronic properties and molecular geometry. The basis set for the computations was 6–311++G(d,p). The IEFPCM solvation method is used to investigate the behavior of the head compound in different solvents. Understanding the interaction between organic compounds and the solvent phase is crucial because the majority of interactions in biological systems occur in solution. UV–Vis spectral analysis of the molecule in different solvents is performed using the TD-DFT method. The compound exhibits more excellent absorption in polar solvents such as water, while its absorption is lower in the gaseous phase. Assessing NLO properties revealed optoelectronics applications. DSOIP-Cl has 5.25 times the first-order hyperpolarizability of urea. Different solvents have higher dipole moments and first-order hyperpolarizability than gases. To identify the inter- and intramolecular charge transfer interactions, intermolecular hydrogen bonding, and hyperconjugative interactions that stabilize the structure, natural bond orbital (NBO) analysis is performed. A stabilization energy of 9.99 kcal/mol is obtained for π(C32–C33) → σ*(C33–C34) due to strong intramolecular hyperconjugative interactions. Frontier molecular orbital (FMO) analysis helps determine the global reactivity parameters and the charge transfer interaction. The van der Waals interaction and steric effect within the molecule are identified using RDG analysis. The pharmacokinetic properties, adherence to drug-likeness criteria, and easily controllable synthesis process were evaluated through ADME analysis, establishing it as an up-and-coming candidate for subsequent drug development. Ultimately, to determine the biological activity and the ability of the title compound to inhibit aldose reductase, a series of computational techniques are employed, including molecular docking study, molecular dynamic (MD) simulation, and MM-PBSA binding energy calculations. −7.86 kcal/mol was reported as the docking score. Hydrophobic interactions play an essential role in the efficiency of protein-ligand binding. The remarkable energetic contribution of DSOIP-Cl to the MM-PBSA binding dynamics highlights its unique association with the AR protein, with a binding energy of −79.81 kJ/mol.

Implementation of energy and gradient for the TDDFT-approximate auxiliary function (aas) method.

In this work, we have implemented the time-dependent density functional theory approximate auxiliary s function (TDDFT-aas) method, which is an approximate TDDFT method. Instead of calculating the exact two-center electron integrals in the K coupling matrix when solving the Casida equation, we approximate the integrals, thereby reducing the computational cost. In contrast to the related TDDFT plus tight-binding (TDDFT+TB) method, a new type of gamma function is used in the coupling matrix that does not depend on the tight-binding parameters. The calculated absorption spectra of silver and gold nanoparticles using TDDFT-aas show good agreement with TDDFT and TDDFT+TB results. In addition, we have implemented the analytical excited-state gradients for the TDDFT-aas method, which makes it possible to calculate the emission energy of molecular systems.

Synthesis and characterization of newly phthalocyanine molecules: Their enzyme inhibition and antioxidant properties, in silico and in vitro

Pcs exhibiting maximum absorption in the phototherapeutic window continue to shine as a beacon of hope in the treatment of cancer. In particular, they maintain skin sensitivity after treatment and can treat deep-seated tumors by stimulating them with broad-spectrum radiation. This makes them advantageous compared to their counterparts. In this study, Novel 1,2,3-triazole schiff base (5a), its methoxy homolog (5b), and their silicon complexes (SiPc-6a and SiPc-6b) were synthesized. Their proposed structures were confirmed by FT-IR, NMR, UV–vis and MS instrumental techniques. Compound (6b) showed inhibitory activity on amylase and glucosidase enzymes. Moreover, considering the glucosidase activity, compound (6b) (IC50, 22.4 ± 1.0 µM) was observed to be more effective than the standard compound (IC50, 186.1 ± 5.8 µM). Molecular docking studies showed that the synthesized compounds bind to the same enzymes with high affinity. The binding energy of SiPc-6a compound with α-amylase, α-glucosidase and tyrosinase enzymes are -10.28, -11.31 and -11.9 kcal/mol, respectively. And another compound, SiPc-6b, has a binding energy of -11.46, -10.11 and -10.27 kcal/mol with a-amylase, a-glucosidase and tyrosinase enzymes, respectively. Based on experimental results that support each other with binding energy values in quality and quantity indicating efficient binding, it is concluded that these compounds can be used in candidate drug discovery. Beside these, as a result of the studies, it was understood that all molecules have antioxidant activity. Additionally, molecular electrostatic potentials, frontier orbital analysis, natural bond orbital (NBO) properties of compounds calculated with DFT and TD-DFT methods and these properties associated with structural properties.

Non-covalent self-assembly of substituted phthalocyanine with C60, C70, and 9-phenylanthracene: Spectroscopic insights and DFT calculations

Self-assembly of non-covalent donor-acceptor systems based on (octakis-3,5-di-tert-butylphenoxy)phthalocyanine (H2Pc(3,5-tBuPhO)8) and С60, С70 or 9-phenylanthracene (PhAn) is observed and described using the UV–vis and steady-state/time-resolved fluorescence methods. The 1:1 stoichiometry of the H2Pc(3,5-tBuPhO)8 - С60/С70/PhAn supramolecule was established by Job's method. The fluorescence quenching of phthalocyanine in the mentioned systems in toluene, indicating close bonding between a donor and an acceptor, was observed. The bonding constants are 1.2 × 104 M−1, 2.4 × 104 M−1, and 3.9 × 102 M−1 for the C60, C70, and PhAn derivatives, respectively. Using time-resolved fluorescence measurements, the static mechanism of quenching was established. The H2Pc(3,5-tBuPhO)8 fluorescence lifetimes in the absence and presence of С60/С70/PhAn, the charge separation rate constant (kCS) and the charge-separated state quantum yield (ΦCS) of donor-acceptor systems were calculated. (С70)H2Pc(3,5-tBuPhO)8 displays the highest kCS and ΦCS in good agreement with its stability parameter. Quantum-chemical calculations of the molecular spatial/electronic structure and the HOMO/LUMO composition that were revealed by DFT and TD DFT methods point to the H2Pc(3,5-tBuPhO)8 → fullerenes redistribution of the electron density and to the opposite one in the PhAn complex.

Theoretical studies on the excited-state properties of di(pyridinyl)methanone-based emitters with efficient thermally activated delayed fluorescence

The excited-state properties of seven thermally activated delayed fluorescence (TADF) emitters with di(pyridinyl)methanone acceptor were investigated using DFT and TD-DFT methods. The results indicate that the species and number of donors strikingly impact the excited-state nature. The mono-substituted donor increases the local-excited singlet (1LE) and local-excited triplet (3LE) contribution, promoting the radiative decay processes and strengthening spin–orbit coupling (SOC) between S1 and T1 states. The decreased charge transfer (CT) contribution of S1 gives rise to a much smaller ΔEST, and the mixed CT-LE nature of T1 guarantees the strong SOC for the designed emitters 1–4 and 6, endowing them with high reverse intersystem crossing rates.

DFT and TDDFT study of Al(III), Ga(III), In(III) porphyrazinates and their perhalogenated derivatives

The effect of perhalogenation (F, Cl) of porphyrazine macrocycle on the molecular structure, electronic and spectral properties of AlIII, GaIII and InIII complexes bearing axial pentafluorophenoxy (C6F5O) group was investigated by DFT and TDDFT methods. Interactions between the axial pentafluorophenoxy group and porphyrazine core were carried out using the Symmetry-Adapted Perturbation Theory (SAPT0) method. According to the calculation results, the nature of the metal atom and peripheral halogenation slightly affect the geometry parameters. Analysis of the simulated spectra showed a bathochromic shift of the Q-band for perchlorinated complexes which correlates with narrowing of the HOMO-LUMO gap.