Molecular Orbital Study Research Articles

Vibrational, theoretical characterisation and In Silico investigation of Norcinnamolaurine: a natural lead for inhibiting AURKA and overcoming immune evasion in Triple-Negative Breast Cancer

ABSTRACT Alkaloids represent a diverse category of natural compounds with noteworthy pharmacological and therapeutic applications. Benzylisoquinoline alkaloids (BIAs) are distinguished by their varied structures and potential medicinal properties. This study specifically investigates Norcinnamolaurine, a BIA found in multiple species and acknowledged for its therapeutic advantages. In the current investigation, we comprehensively analyzed Norcinnamolaurine, encompassing Frontier Molecular Orbital studies, vibrational spectroscopy, nonlinear optical properties, natural bond orbital evaluations, and Fukui's analysis. Additionally, we executed an E-pharmacophore-based screening utilizing the AURKA-Norcinnamolaurine complex. The generated hypothesis underwent database screening; lead compounds from the Natural Product and Drug Bank databases exhibited enhanced binding affinities ranging from −8.602 to −7.148 kcal/mol, demonstrating improved interactions within the AURKA binding pocket. Subsequently, the identified lead compounds were subjected to further analysis via MMGBSA, DFT, and Molecular Dynamics Simulations (MDS). Our findings indicate that Norcinnamolaurine exhibits a superior binding affinity towards the target protein. Significant outcomes were also observed in the vibrational and FMO studies. Moreover, MDS analysis revealed that the resultant complexes maintained relative stability, exhibiting minimal deviation and fluctuations. This stability was corroborated through additional assessments using MMPBSA and PCA/FEL methodologies.

Research design, evaluation, and in vitro assessment of N'-(thiophene-2-carbonyl) pyridine-4-carbohydrazide as a biological agent

The study addresses the synthesis and characterisation of the chemical N'-(thiophene-2-carbonyl) pyridine-4-carbohydrazide (TPCPC), which was created by mixing thiophene-2-carboxylic acid with pyridine-4-carbohydrazide. The reaction was catalyzed using N,N'-tetramethyluronium tetrafluoroborate (TBTU). Various spectroscopy approaches were utilized to characterize the chemical. TPCPC demonstrated considerable biological activity, with stronger anti-inflammatory effects than diclofenac sodium and more efficient antidiabetic actions than acarbose. Computational study, notably molecular docking, found many hydrogen-bonding interactions with α-amylase and favorable interactions involving prostaglandin h2 synthase-1 and cyclooxygenase-2, supporting possible medical uses. Density Functional Theory (DFT)-based frontier molecular orbital study results focused on TPCPC's stability and reactivity. The electrical characteristics and binding sites of the molecule were further investigated through molecular electrostatic potential, ELF&LOL, and Mulliken charges distribution. The oral rat LD50 for TPCPC was also predicted using the Toxicity Estimation Software Tool (T.E.S.T.). This comprehensive study enhances our understanding of TPCPC's unique features and potential uses in various domains.

Novel AIE and solvatochromism exhibiting TPE based organic fluorophore with excellent emission properties in solid and solution phase for latent fingerprint and metronidazole sensing in real samples

Organic molecules with extended aromaticity are important when designing probes with optical properties. Herein, we designed and synthesized a novel tetraphenylethylene (TPE) based organic molecule TC exhibiting excellent photophysical characteristics. A thorough and in-depth study of the optical properties of probe TC was performed including solvatochromism, aggregation and solid-state studies using ultraviolet–visible (UV Vis) and fluorescence spectroscopy. Also, its optical properties under a UV 365 nm laser were investigated. The compound exhibited aggregation induced emission (AIE) which was thoroughly investigated in a H2O/DMF system and later utilized in formulation of invisible ink and latent fingerprint sensing. Moreover, the excellent emission properties of probe TC were utilized for the highly selective detection of the antibiotic metronidazole (MET) in real samples including human serum and artificial urine. Furthermore, portable TLC and paper-based strips were designed for the on-site detection of MET. Additionally, the mechanism of selective sensing of MET was thoroughly investigated through spectroscopic studies including titration NMR, fluorescence, UV Vis studies and DFT studies. Photoinduced electron transfer (PET) was attributed as the plausible sensing mechanism for the detection of MET. Scanning electron microscopy (SEM) also supported the sensing of MET through change in morphology. DFT calculations involved the measurement of thermodynamic stability, reduced density gradient (RDG) analysis, molecular orbital, and charge transfer studies as well as analysis of quantum theory of atoms in molecules (QTAIM). All the studies supported the presence of non-covalent interactions between probe TC and MET.

Exploring the impact of heterocyclic bridges for tuning the amplitudes of Nonlinear optical properties under Gas, IEFPCM and COSMO solvent models

Nonlinear optical (NLO) materials are a distinctive class of materials due to their NLO response and wide range of applications. We present a systematic quantum chemical study for designing triphenylamine based derivatives (1Ph to 3PhDTDZ) by modifying central bridge with various size and types of heterocyclic rings. Density functional theory (DFT) method is used to calculate the NLO properties including linear and third-order NLO polarizabilities (α and γ) by using M06-2X functional coupled with the 6-311G** basis set. The calculation results predict that among the designed compounds, 1PhDTDZ has the highest third-order NLO polarizability of 2347.7 x 10−36 esu and lowest transition energy of 1.828 eV. On the other hand, 3PhDTDZ has a greater amplitude (108.5 x 10−24 esu) of static linear polarizability (αiso). We also computed frequency-dependent third-order NLO polarizability values at various laser wavelengths (1500 nm to 1970 nm). This provides valuable information about the complex interaction between light and matter. Dynamic second hyperpolarizability of electro-optic Pockels effect (EOPE effect, (γ (−ω; ω,0,0)) is calculated at 1500 nm laser wavelength with a larger γ-amplitude of 36708.4 x 10−36 esu. The effect of solvent on α and γ has also been the primary focus of this research. An extensive solvation impact has been studied using integral equation formalism Polarizable Continuum Model (IEFPCM) and Conductor-like Screening Model (COSMO). Magnitudes of αiso and 〈γ〉 have shown variation from gas to solvent methods. While among solvents, amplitudes are seen 3.87 % to 11.29 % greater under the effect of COSMO-methanol than PCM-methanol. The Frontier molecular orbital (FMO) studies found a significant decrease in energy band gaps from 5.75 eV to 2.98 eV. Since our systems exhibit remarkable photovoltaic properties, they can be used as dye-sensitized solar cells (DSSCs). Their open circuit voltage (VOC) ranging from 1 eV to 4 eV. Thus, our designed triphenylamine based derivatives with distinct central heterocyclic bridges showcase remarkable efficiency as NLO materials, with additional benefits of exhibiting good photovoltaic properties.

Experimental and theoretical investigation on vibrational, electronic, and docking characteristics of 1-(3-nitro-phenyl)-5-phenyl-penta-2,4-dien-1-one (1NP5PP)

The 1-(3-nitro-phenyl)-5-phenyl-penta-2,4-dien-1-one (1NP5PP) molecule is subjected to detailed spectroscopic investigation by analyzing the spectra obtained by FT-IR and FT-Raman methods. The computational analysis were performed at DFT level using B3LYP/6-311++G(d, p) basis set. With the support of potential energy distribution the entire vibrational assignment was conducted. A frontier molecular orbital study reveals energy gap is small for the molecule. Molecular electrostatic potential surface shows that highest electronegative around oxygen atom in ethylenic bridge and electropositive region spreads through all the hydrogen atoms in the molecule. Natural bond orbital, nonlinear optical analysis, and Fukui function studies were conducted for the present molecule. The electron distribution and reactive site on the surface of the molecule were analyzed using electron localization function and localized orbital locator analysis. In molecular docking studies the interaction observed between MPRO and the 1NP5PP ligand shows the good degree of inhibition. The above mentioned analogy reflects that 1NP5PP has adequate biological properties.

Exploration of sensing behavior B3O3 quantum dot toward methyl halides; a quantum chemical approach

In this study, B3O3 quantum dot has been used for sensing of various methyl halides for the first time. The suitable cavity of B3O3 makes it more suitable for the sensing of variety of analytes. The three, very simple and most important methyl halides (CH3F, CH3Cl and CH3Br) are selected to adsorb on B3O3 surface. Density functional theory (DFT) method with appropriate basis set was implemented. Among the considered complexes, methyl bromide complex CH3Br@B3O3) showed higher interaction energy of −16.90 kcal mol−1. The noncovalent interaction (NCI) analysis identified the existence of van der Waals interactions among all analytes and adsorbent. The density of state (DOS) and natural bond orbital (NBO) charges analyses identified the charge transfer and conductive properties of B3O3 nanosheet after interaction with alkyl halides. Frontier molecular orbital study revealed the electronic attributes of considered complexes. It is revealed that B3O3 quantum dot can be a very good choice for sensing of methyl halides and could be helpful for monitoring and reducing the environmental pollution.

Tailored nanocones arrays on cellulose fiber: A higher-performance flexible SERS substrate for trace chemical detection

This study presents the successful fabrication of silver nanocone surface-enhanced Raman spectroscopy (SERS) substrate on flexible 70 GSM paper using the Direct Current (DC) magnetron sputter deposition technique. XRD analysis confirmed the crystalline nature and face-centered cubic structure of the Silver Nanocone (AgNC) substrate. SEM analysis revealed the fabricated AgNC substrate shows nanocones arrayed on the cellulose fibers. UV–visible spectral analysis validates the surface plasmon resonance peak of the AgNC substrate at 406 nm. Furthermore, SERS spectral analysis showed excellent detection abilities by accurately identifying rhodamine 6G and methylene blue dyes and fipronil pesticides at concentrations of 10−9 M, 10−8 M, and 10−6 M respectively. In addition, the substrate detects fipronil (pesticide) sprayed on tomatoes and nicotine (energy booster) mixed with tea for commercial applications. The substrate exhibits enhancement factor values for rhodamine 6G, methylene blue, fipronil, and nicotine as 1.3 × 107, 1.2 × 106, 2.6 × 105, and 5.8 × 104, respectively. Theoretical validation using density functional theory confirms the experimental Raman and SERS peaks show good similarity. Considering that the charge transfer mechanism shown in the study of the frontier molecular orbitals allowed for the identification of the interaction between the analyte molecules and silver cluster. The fabricated SERS substrate exhibited remarkable stability and reproducibility.

On the rearrangement and dissociation mechanism of SiH4+ in its triply-degenerate ground state.

An abinitio molecular orbital study has been performed to explore the structural rearrangement and dissociation of SiH4+ radical cation at the X̃2T2 ground electronic state. All stationary points located on the lowest adiabatic sheet of Jahn-Teller (JT) split X̃2T2 state are fully optimized and characterized by performing harmonic vibrational frequency calculations. The structural rearrangement is predicted to start with JT distortions involving the doubly-degenerate (e) and triply-degenerate (t2) modes. The e mode reduces the initial Td symmetry of the SiH4+ ground state to a D2d saddle point, which eventually dissociates into the SiH3+(2A1) + H products via C3v local minimum. In turn, an e-type bending of αH-Si-H yields the SiH2+(2A1) + H2 products through the first C3v local minimum and then the Cs(2A') global minimum. In the alternative pathway, the t2 mode distorts the initial Td symmetry into a loosely bound C3v local minimum, which further dissociates into the SiH3+(2A1) + H asymptote via totally symmetric Si-H stretching mode, and SiH2+(2A1) + H2 products via H-Si-H bending (e) mode through the Cs(2A') global minimum. It is further predicted that the Cs global minimum interconverts equivalent structures via a C2v transition structure. In addition, the two dissociation products are found to be connected by a second C2v transition structure.

Low-Migration Compounds with Amine Functionality as Coinitiators of Radical Polymerization.

The utilization of two-component systems comprising camphorquinone (CQ) and aromatic amines has become prevalent in the photopolymerization. However, there are still concerns about the safety of this CQ/amine system, mainly because of the toxicity associated with the leaching of aromatic amines. In light of these concerns, this study aims to develop novel coinitiator combinations featuring CQ and amines which cannot be leached out of materials, enabling free radical polymerization of representative dentalmethacrylate resins under blue light irradiation. This approach involves the initial design and analysis of hydrogen donors with low C─H bond dissociation energy through molecular modeling. Subsequently, copolymerizable methacrylate functional groups are incorporated via chemical modification, allowing it to act as both coinitiator and copolymerization monomer to achieve low migrationand leachability properties. This work presents, for the first time, the synthesis of the innovative coinitiator and compares its performance with the benchmark CQ/ethyl-4-dimethylaminobenzoate (EDB)-based photoinitiation system (PIS). The results demonstrate the effectiveness of the newly proposed PIS. Finally, an in-depth investigation is conducted into the reaction mechanism associated with this PIS through molecular orbital calculations and electron spin resonance studies.

Molecular structure, optical, first-order hyper polarizability, electronic properties, reactivity (ELF and LOL) − computational analysis using DFT and Multiwfn for 2, 3-diaminopyridinium selenate

A detailed study on the first principle calculations of 2,3-diaminopyridinium selenite (2,3-DAPS) – an organometallic salt has been performed using B3LYP/6–311++G(d,p). Single crystal X-ray diffraction (XRD) analysis confirms that the crystal formed exhibits a monoclinic crystal structure, specifically belonging to the centrosymmetric space group P21/c. The obtained primitives and interfacial angles are as follows: a = 7.4978(15)Å, b = 7.6681(15) Å, c = 14.314(3) Å, α = γ = 90°, β = 93.75(3)°, and the volume of the unit cell V = 821.2(3) (Å)3. The structure was optimized with a global minimum. The natural bonding orbital charge transfer studies between the cation and anion was performed to gain insights into their electronic interactions. Energy gap and other global chemical reactivity descriptors have been computed with the aid of molecular orbital studies. The influence of solvent on the absorption spectra provided the evidence of solvent–solute interactions and their impact on the electronic transitions within the molecule. The presence of electrophilic and nucleophilic reactivity in the chemical is indicated by the molecular electrostatic potential (MEP) map. From the nonlinear optical (NLO) studies, it has been found that the first-order hyperpolarizability value is 30.771 × 10−31 esu, which is 8.252 times that of urea. This suggests that the compound may be a better non-linear optical material and suitable for laser applications. To calculate the proportion of intermolecular interactions and examine the distribution compound's electrostatic potential, a Hirshfeld surface analysis was conducted. The analysis provided insights into the spatial arrangement of molecules and their interactions. Additionally, topology path calculations elucidated the intrinsic connectivity between critical points, shedding light on the bonding characteristics within the compound. The likelihood of electron density at bonding and anti-bonding sites was also determined using the Electron Localization Function (ELF) and Localised Orbital Locator (LOL) plots. These analyses aided in understanding the electron distribution and the nature of chemical bonding within the compound, providing valuable information about its electronic structure and reactivity.

Quantum chemical, vibrational, microhardness, thermal and antibacterial studies on polymorphic drug crystal: Sulfanilamide (β-form)

The widely known pharmaceutical drug compound, Sulfanilamide, crystallized in the β-form of its polymorphic phases by slow evaporation of the parent solution at room temperature. The single crystal X-ray diffraction study provided information about the cell parameters, confirming the β-phase of the compound. Optimization of the molecule by quantum chemical computations, viz., Hartree-Fock (HF) Theory and Density Functional Theory (DFT) using the B3LYP function with 6–311++G(d,p) basis set for both in restricted methods were carried out. The Frontier Molecular Orbital studies gave the HOMO and LUMO values, and Mulliken charge analysis showed the possible charge delocalization and donor-acceptor sites. Vibrational bands of the functional groups present in the β-Sulfanilamide compound were identified and investigated using FT-IR and FT-Raman spectroscopy in the range of 4000–400 cm−1. The grown crystal was transparent in the entire UV region with a lower cut off wavelength of 241 nm as investigated by the UV–Vis-NIR analysis. Thermogravimetric and differential thermal analyses of the compound were carried out and the results were plotted as TGA/DTA graph. Microhardness tests were used to determine the mechanical parameters of this pharmaceutical compound. Sulfanilamide, a well-known antibacterial agent and used to treat a variety of bacterial infections, was tested using the zone inhibition method and the antibacterial activity was confirmed.

Novel disposable screen-printed sensors based on copper oxide nanoparticles for sensitive voltammetric assay of antazoline

The fabrication and electroanalytical validation of a novel homemade screen-printed carbon electrode enriched with copper oxide nanoparticles (CuONPs/SPCEs) were demonstrated for sensitive and selective voltammetric determination antazoline (ANT) in eye drop solution and spiked serum samples. With a reported electrocatalytic activity, CuONPs catalyzed the oxidation of ANT at the electrode surface showing an irreversible anodic oxidation peak at 0.9 V under a diffusion-controlled electrode reaction. Based on the electroanalytical and molecular orbital calculation studies, oxidation of ANT molecule undergoes via oxidation of the aliphatic nitrogen atom within the ANT moiety. Linear calibration curves were illustrated covering the ANT concentration ranged from 0.01 to 3.819 µg mL−1 with and limit of detection 3 ng mL−1. The fabricated sensors enriched with CuONPs exhibited high fabrication and measurement reproducibility with a prolonged shelf lifetime (6 months). The electroanalytical approach presented adequate sensitivity and selectivity with a short analysis time, applying low-cost instrumentation and simple pretreatment protocol avoiding handling hazardous organic solvents. Trace ANT was monitored in the presence of different interfering species, degradation products, and xylometazoline hydrochloride (ZYL) in the co-formulated ophthalmic pharmaceutical samples. The CuONPs based voltammetric sensors were introduced as a reliable eco-friendly analytical tool for monitoring ANT in ophthalmic solutions and biological fluids with acceptable recovery values.

Exploring the Efficacy of Noncovalent SARS-CoV-2 Main Protease Inhibitors: A Computational Simulation Analysis Study.

The SARS-CoV-2 main protease, as a key target for antiviral therapeutics, is instrumental in maintaining virus stability, facilitating translation, and enabling the virus to evade innate immunity. Our research focused on designing non-covalent inhibitors to counteract the action of this protease. Utilizing a 3D-QSAR model and contour map, we successfully engineered eight novel non-covalent inhibitors. Further evaluation and comparison of these novel compounds through methodologies including molecular docking, ADMET analysis, frontier molecular orbital studies, molecular dynamics simulations, and binding free energy revealed that the inhibitors N02 and N03 demonstrated superior research performance (N02 ΔGbind=-206.648 kJ/mol, N03 ΔGbind=-185.602 kJ/mol). These findings offer insightful guidance for the further refinement of molecular structures and the development of more efficacious inhibitors. Consequently, future investigations can draw upon these findings to unearth more potent inhibitors, thereby amplifying their impact in the treatment and prevention of associated diseases.

DFT study on the effects of substituents on the structure and properties of dithiophosphate collectors

AbstractThe structures and properties of seven substituted dithiophosphate (DTP) collectors containing three types of functional groups (O2PS2, C2PS2, and N2PS2) were studied using density functional theory. The collectors studied were dibutyl dithiophosphate (DNBDTP), diisobutyl dithiophosphate (DIBDTP), dibutoxyethyl dithiophosphate (DBOEDTP), xylenol dithiophosphate (DMPDTP), diisobutyl dithiohypophosphite (3418A), diphenylamine dithiophosphate (DTADTP), and dicyclohexylamine dithiophosphate (DCADTP). The structural analysis showed that the PS bond lengths in the C2PS2 and N2PS2 types are longer than those in the O2PS2 type, indicating that the strength of the PS bond is weaker in the former two. The frontier molecular orbital studies showed that the energy differences between the highest occupied molecular orbitals (HOMO) of 3418A (C2PS2 type) and DCADTP (N2PS2 type) and the lowest unoccupied molecular orbital (LUMO) of galena are significantly lower than those of the other collectors, suggesting that C2PS2 type and N2PS2 type with cyclohexane could enhance the interaction with galena. Using the Fukui function to calculate the nucleophilicity and electrophilicity of the sulfur atom indicated that the S atom exhibits nucleophilicity, especially in DMPDTP and DTADTP, which contain benzene rings, and the S atom exhibits strong nucleophilicity without electrophilicity. However, due to the lack of contribution from S atoms to the LUMO orbitals, the S atoms in these two compounds are not participate in any LUMO reactions. The adsorption results demonstrated that 3418A (C2PS2 type) and DCADTP (N2PS2 type) exhibit the strongest adsorption on Pb2+ ions, while DMPDTP (C2PS2 type) and DTADTP (O2PS2 type) which contain benzene rings, as well as DBOEDTP (C2PS2 type) which does not contain a benzene ring, exhibit weaker interaction compared to the other compounds. These are consistent with the results of the frontier molecular orbital and electrophilic nucleophilicity calculations.

Molecular structure, different solvents interaction, thermodynamic, electronic, topological, and chemical behaviors of cis-2,6-dimethylpiperazin- anti depression agent

The Cis-2,6-Dimethylpiperazin has undergone wave function analysis to determine the topological characteristics. The vibrational and ultraviolet-visible spectroscopy investigations were carried out. By advocating Density Functional Theory as a technique, the optimized structure is computed. Polarizability, nucleophilicity, and electrophilicity have also been estimated using Non-Linear Optics, Fukui, and Molecular Electro Static Potential. Additionally, the Highest occupied molecular orbital to Lowest unoccupied molecular orbital studies were carried out to know biological activity. It has been hypothesized that drug-like properties can explain a biological reaction. We predicted and examined the various thermodynamic properties. In addition to previous studies, the docking process was employed to calculate the energies of binding and size of bonding hydrogen with various proteins. This work describes molecular, electrical, chemical, and biological actions.

Exploring the Molecular Mechanism of the Antioxidant Activity of Medicine and Food Homology Licorice Flavonoids Based on Pharmacophore Theory and Quantum Calculations

Licorice flavonoids are a kind of flavonoids extracted from the root of licorice, which have good antioxidant activity and are widely used in the food industry. In the early research of the research group, it has been found that the antioxidant activity of licorice flavonoids can be altered by solvent mediation. However, the molecular mechanism underlying the antioxidant properties of licorice flavonoids is still not fully understood. Therefore, this study aims to explore the molecular mechanism underlying the antioxidant activity of licorice flavonoids based on the principles of pharmacophore theory and quantum computing. Firstly, network pharmacology will be employed to study the antioxidant properties of licorice flavonoids. The major active components and key structural features responsible for the antioxidant activity in licorice flavonoids will be screened using pharmacophore theory and further validated through molecular docking. Lastly, quantum computing will be utilized to uncover the potential mechanism underlying their antioxidant activity. Pharmacophore studies have shown that licochalcone B, retrochalcone, isoliquiritin, and isoliquiritigenin exhibit low predicted IC50 values, indicating that these compounds are key components of licorice flavonoids in the antioxidant process. Molecular electrostatic potential (MEP) and frontier molecular orbital studies have shown that licochalcone B, retrochalcone, isoliquiritin, and isoliquiritigenin all exhibit certain chemical reactivity. Quantum computing studies have found that the para-phenol hydroxyl group on the core structure of licochalcone B, isoliquiritigenin, retrochalcone, and isoliquiritin is a crucial functional group for the antioxidant activity of flavonoid compounds. In general, this study successfully elucidated the mode of action of licorice flavonoids in the antioxidant process, providing some guidance for the synthesis of new antioxidant compounds.

Approach toward Low Energy Loss in Symmetrical Nonfullerene Acceptor Molecules Inspired by Insertion of Different π-Spacers for Developing Efficient Organic Solar Cells.

In this quantum approach, by adding bridge/π-spacer fragments between the donor and acceptor parts of a newly constructed DF-PCIC (A-D-A type) molecule, it is the aim to improve the photovoltaic characteristics of organic solar cells (OSCs). After π-spacer insertion into the reference molecule (DF-R), six new molecules (DF-M1 to DF-M6) were designed. The optoelectronic attributes of newly inspected molecules were theoretically calculated using MPW1PW91/6-31G(d,p) level of theory. All newly proposed molecules possessed a lower band gap (Eg), a higher value of absorption, lower reorganization energy, greater dipole moment, and lower energies of excitations than the DF-R molecule. The frontier molecular orbital study proclaimed that the DF-M1 molecule has the lowest band gap of 1.62 eV in comparison to the 2.41 eV value of DF-R. Absorption properties represented that DF-M1 and DF-M2 molecules show the highest absorption values of up to 1006 and 1004 nm, respectively, in the near-infrared region. Regarding the reorganization energy, DF-M2 has the lowest value of λe (0.0683896 eV) and the lowest value of λh (0.1566471 eV). DF-M2 and DF-M5 manifested greater dipole moments with the values of 5.514665 and 7.143434 D, respectively. The open circuit voltage (VOC) of all the acceptors was calculated with J61, a donor complex. DF-M4 and DF-M6 molecules showed higher values of VOC and fill factor than the DF-R molecule. Based on the given results, it was supposed that all the newly presented molecules might prove themselves to be better than the reference and thus might be of great interest to experimentalists. Thus, they are suggested to be used to develop proficient OSC devices with improved photovoltaic prospects in the near future.

Frequency-dependent nonlinear optical response and refractive index investigation of lactone-derived thermochromic compounds

Nonlinear optical (NLO) switchable materials play a crucial role in the fields of electronics and optoelectronics. The selection of an appropriate switching approach is vital in designing such materials to enhance their NLO response. Among various approaches, thermos-switching materials have shown a 4-fold increase in NLO response compared to other photo-switching materials. In this study, we computationally investigated the geometric, electronic, and nonlinear optical properties of reversible lactone-based thermochromic compounds using the ωB97XD/6-311+G (d,p) level of theory. Molecular orbital studies are employed to analyze the electronic properties of the close and open isomers of these compounds, while time-dependent density functional theory (TD-DFT) analysis is utilized to evaluate their molecular absorption. Our findings reveal that the π-electronic conjugation-induced delocalization significantly influences the ON-OFF switchable nonlinear optical response of the lactone-based thermochromic compounds. Notably, among all compounds, the open isomer of lactone 2 exhibits the highest hyperpolarizability value (6596.69 au). Furthermore, we extended our analysis to investigate the frequency-dependent second and third-order hyperpolarizabilities. The most pronounced frequency-dependent NLO response is observed at 532 nm. Additionally, we calculated the refractive index of these thermochromic compounds to further assess their nonlinear optical response. The open isomer of lactone 1 demonstrates the highest refractive index value (3.99 × 10−14 cm2/W). Overall, our study highlights the excellent potential of reversible thermochromic compounds as NLO molecular thermos-switches for future applications.

Identification of natural product as selective PI3Kα inhibitor against NSCLC: multi-ligand pharmacophore modeling, molecular docking, ADME, DFT, and MD simulations.

Non-small cell lung cancer (NSCLC) is a widespread and often aggressive form of cancer affecting people worldwide. PIK3CA missense mutations play a significant role in the progression of growth factor signaling in cancer, making PI3Kα an important biological target for inhibition against NSCLC. Natural product molecules with PI3Kα inhibitory activity are promising therapeutic agents for the treatment of NSCLC, owing to their selectivity and potentially lower toxicity compared to synthetic compounds. To discover new natural product molecules, we integrated ligand-based virtual screening with structure-based virtual screening. We developed a multi-ligand pharmacophore hypothesis, validated it with 3D Field-based QSAR, and screened a Natural-Product-Based Library (ChemDiv) containing 3601 molecules. After initial screening, 137 hit molecules were generated and further screened using the extra precision (XP) Glide docking protocol. The best ten molecules were selected for free binding energy (ΔG) analysis using MMGBSA and ADME predictions. For further optimization, the top four hits were subjected to induced fit docking (IFD), quantum chemical descriptors analysis by Frontier Molecular Orbital (FMO) studies, and a 100ns molecular dynamics (MD) simulation. The compounds-S721-1955, CM4579-5085, S721-1963, and S721-1999-exhibited better results than the PI3Kα selective inhibitor alpelisib. In silico prediction analysis of S721-1955 and alpelisib revealed that the former exhibited superior selectivity theoretically, as evidenced by its higher affinity for the target protein. The selective natural product molecule identified in this study holds promise as a potential anti-cancer drug against NSCLC in the near future, but further in vitro and in vivo studies are necessary to confirm its efficacy.

Possible role of essential tyrosine on the protonation of isoalloxazine ring in the excited singlet state and the triplet state in photolyase from Escherichia coli. Molecular orbital study

Photolyases from Escherichia coli. (PLEC) function to repair UV-damaged DNA. Photolyases and cryptochromes (altogether 42 proteins) are found to contain at least one tyrosine (Tyr) residue near the isoalloxazine ring (Iso) of flavin adenine dinucleotide (FAD) within 1.2 nm, Tyr281 in PLEC. Iso in PLEC is surrounded by four Trp residues and one Tyr within 1.2 nm from Iso. Photoinduced charge transfer interactions (PCT) among these chromophores in the Iso-Tyr281-Trp277-Trp338-Trp382-Trp384 system were studied by means of a semi-empirical molecular orbital (MO) method. Structure of the system was extracted from crystal structure of PLEC. In the ground state the PCT interactions between any pairs were negligible. Upon photo-excitation almost one electron transferred from Trp382 to the excited Iso, to which an electron transport chain from Tyr residues at the protein - water interface to Iso is connected. Protonation at N1 or N5 of Iso from Tyr281 markedly stabilized the transition energy in the excited singlet state and triplet state, depending on the polarity of the medium, but not from a source other than Tyr281. In these states, nearly one electron migrates from Tyr281 to Trp382. Effects of the protonation from Tyr281 to the fully reduced Iso were also examined, where total charge of the system was −2. In the ground state the energy of the system was stabilized by the protonation, when the proton was bound to N5 of Iso, but not to N1. In the excited singlet state and triplet state of the fully reduced Iso, the transition energies of the system were also stabilized upon the protonation to N1 or N5 of Iso from Tyr281, but not from a source other than Tyr281. In the ground state almost two negative charges were located at Iso. In the excited singlet state one of two negative charges was mostly localized to Iso and another to Trp277 at the dielectric constant, 3, and to Trp384 at the dielectric constant, 10. In the triplet state without the protonation, one of two negative charges was localized to Iso and another to Trp384 at any dielectric constant. Upon protonation to N1 or N5 of Iso in the triplet state, one of the negative charges was localized to Iso and another to Tyr281 at any value of dielectric constant. Thus Tyr281 closely interacted with Iso in the excited singlet state and triplet state, and other Trp residues in the system through the proton transfer.