Investigation of embelin synthetic hybrids as potential COVID-19 and COX inhibitors: Synthesis, spectral analysis, DFT calculations and molecular docking studies.

Embelin (2, 5-dihydroxy-3-undecyl-1,4-benzoquinone), a benzoquinone isolated from fruits of Embelia ribes has miscellaneous biological potentials including; anticancer, anti-inflammation, antibiotic, and anti-hyperglycemic activities. Also, embelin down-regulates the overexpression of inflammatory pathways like NF-kB, TACE, TNF-α, and other cytokines. Furthermore, embelin fascinated synthetic interest as a pharmacologically active compound. The present article involves the design, synthesis, DFT calculations, and molecular docking studies of embelin derivatives as cyclooxygenase inhibitors of embelin derivatives. The structure of these derivatives is confirmed by the various spectral analyses such as IR, NMR, and Mass. The DFT calculations were carried out for the molecules (1-8) using CAM-B3LYP hybrid functional with a 6-31+g(d) all-electron basis set using the Gaussian 09 package. Second-order harmonic vibrational calculations are used to check the minimum nature of the geometry. Further, HOMO and LUMO analyses were used for the charge transfer interface between the structures. Based on our previous work and structural activity relationship study, foresaid embelin derivatives were evaluated for in vitro COX-1 and COX-2 inhibitory activity. The compounds 3, 4, 7, and 8 demonstrated excellent COX inhibitions with IC50 values of 1.65, 1.54, 1.56, and 1.23 µM compared to standard drugs Celecoxib and Ibuprofen. Finally, the molecular docking studies carried out with Covid-19 and cyclooxygenase with all the newly synthesized embelin derivatives.

Investigation of NPB Analogs That Target Phosphorylation of BAD-Ser99 in Human Mammary Carcinoma Cells.

The design and development of a small molecule named NPB [3-{(4(2,3-dichlorophenyl)piperazin-1-yl}{2-hydroxyphenyl)methyl}-N-cyclopentylbenzamide], which specifically inhibited the phosphorylation of BAD at Ser99 in human carcinoma cells has been previously reported. Herein, the synthesis, characterization, and effect on cancer cell viability of NPB analogs, and the single-crystal X-ray crystallographic studies of an example compound (4r), which was grown via slow-solvent evaporation technique is reported. Screening for loss of viability in mammary carcinoma cells revealed that compounds such as 2[(4(2,3-dichlorophenyl)piperazin-1-yl][naphthalen-1-yl]methyl)phenol (4e), 5[(4(2,3-dichlorophenyl)piperazin-1-yl][2-hydroxyphenyl)methyl)uran-2-carbaldehyde (4f), 3[(2-hydroxyphenyl][4(p-tolyl)piperazin-1-yl)methyl)benzaldehyde (4i), and NPB inhibited the viability of MCF-7 cells with IC50 values of 5.90, 3.11, 7.68, and 6.5 µM, respectively. The loss of cell viability was enhanced by the NPB analogs synthesized by adding newer rings such as naphthalene and furan-2-carbaldehyde in place of N-cyclopentyl-benzamide of NPB. Furthermore, these compounds decreased Ser99 phosphorylation of hBAD. Additional in silico density functional theory calculations suggested possibilities for other analogs of NPB that may be more suitable for further development.

Luminescent Gold Nanorods To Enhance the Near-Infrared Emission of a Photosensitizer for Targeted Cancer Imaging and Dual Therapy: Experimental and Theoretical Approach.

Strong plasmon absorption in the near-infrared (NIR) region renders gold nanorods (GNRs) amenable for biomedical applications, particularly for photothermal therapy. However, these nanostructures have not been explored for their imaging potential because of their weak emission profile. In this study, the weak fluorescence emission of GNRs is tuned to match that of the absorption of a photosensitizer (PS) molecule, and energy transfer from the GNR to PS enhances the emission profile of the GNR-PS combination. GNR complexes generally quench the fluorescence emission of nearby chromophores. However, herein, the complex retains or rather enhances the fluorescence through competition in energy transfer. Excitation-dependent energy transfer has been explained experimentally and theoretically by using DFT calculations, the CIE chromaticity diagram, and power spectrum. The final GNR-PS complex modified for tumor specificity serves as an excellent organ-specific theranostic probe for bioimaging and dual therapy both in vitro and in vivo. Principal component analysis designates photodynamic therapy a better candidate than that of photothermal therapy for long-term efficacy in vivo.

Computational studies on ground and excited state charge transfer properties of peptidomimetics.

Chemical modifications at various peptide positions result in peptidomimetics with unique physical and chemical properties that can be used for a range of applications. Among many peptidomimetics, ureidopeptides are interesting due to their ability to act as donor-bridge-acceptor systems through which charge transfer occurs in one direction and can be triggered by an electrochemical pulse without perturbing the nuclear position. In this regard, some UP mimetics with different chromophoric units are studied in this work to understand their role using DFT based methods. Computational results and natural charge analysis provide evidence for the extensive contribution of the substituents to the excitation and hole migration dynamics. Further, the results show that the UP backbone preserves its uni-directional charge transfer phenomenon from the ureido to carboxylate terminal irrespective of the terminal groups and position. However, the substituent affects the excitation energies and the time scales of the hole migration. Among the substituents studied here, fluorine migrates to the hole within a shorter time scale while phenyl groups take longer.

On the ultrafast charge migration and subsequent charge directed reactivity in Cl⋯N halogen-bonded clusters following vertical ionization.

In this article, we have presented ultrafast charge transfer dynamics through halogen bonds following vertical ionization of representative halogen bonded clusters. Subsequent hole directed reactivity of the radical cations of halogen bonded clusters is also discussed. Furthermore, we have examined effect of the halogen bond strength on the electron-electron correlation- and relaxation-driven charge migration in halogen bonded complexes. For this study, we have selected A-Cl (A represents F, OH, CN, NH2, CF3, and COOH substituents) molecules paired with NH3 (referred as ACl:NH3 complex): these complexes exhibit halogen bonds. To the best of our knowledge, this is the first report on purely electron correlation- and relaxation-driven ultrafast (attosecond) charge migration dynamics through halogen bonds. Both density functional theory and complete active space self-consistent field theory with 6-31 + G(d, p) basis set are employed for this work. Upon vertical ionization of NCCl⋯NH3 complex, the hole is predicted to migrate from the NH3-end to the ClCN-end of the NCCl⋯NH3 complex in approximately 0.5 fs on the D0 cationic surface. This hole migration leads to structural rearrangement of the halogen bonded complex, yielding hydrogen bonding interaction stronger than the halogen bonding interaction on the same cationic surface. Other halogen bonded complexes, such as H2NCl:NH3, F3CCl:NH3, and HOOCCl:NH3, exhibit similar charge migration following vertical ionization. On the contrary, FCl:NH3 and HOCl:NH3 complexes do not exhibit any charge migration following vertical ionization to the D0 cation state, pointing to interesting halogen bond strength-dependent charge migration.

Charge-transfer complexation between naphthalene diimides and aromatic solvents.

Naphthalene diimides (NDIs) form emissive ground-state charge-transfer (CT) complexes with various electron rich aromatic solvents like benzene, o-xylene and mesitylene. TD-DFT calculation of the complexes suggests CT interaction and accounts for the observed ground-state changes.

Correction: Molybdenum-maltolate as a molybdopterin mimic for bioinspired oxidation reaction.

Correction for 'Molybdenum-maltolate as a molybdopterin mimic for bioinspired oxidation reaction' by Swapnil S. Pawar et al., Dalton Trans., 2024, 53, 5770-5774, https://doi.org/10.1039/D3DT04296K.

Molybdenum-maltolate as a molybdopterin mimic for bioinspired oxidation reaction.

A novel cis-dioxomolybdenum(VI)-maltolate [MoO2(Mal)2] (1) is prepared as a stable molybdopterin model for the biomimetic catalysis of the oxidation of hypoxanthine in acetonitrile-water at room temperature. Compound 1 efficiently catalyzes the oxidation reaction of toluene, diphenylmethane, and styrene. Cyto- and oral-toxicity studies suggest its tremendous potential for application as a molybdenum supplement.

Methane formation from the hydrogenation of carbon dioxide on Ni(110) surface--a density functional theoretical study.

The complete hydrogenation mechanisms of CO2 are explored on Ni(110) surface catalyst using density functional theory. We have studied the possible hydrogenation mechanism to form product methane from the stable adsorption-co-adsorption intermediates of CO2 and H2 on Ni(110) surface. Our computations clearly elucidate that the mechanism for the formation of methyl, methoxy and methane moieties from carbon dioxide on the nickel catalyst. Moreover, our studies clearly show that the methane formation via hydroxyl carbonyl intermediate requires a lower energy barrier than via carbon monoxide and formate intermediates on the Ni(110) surface.

Density functional theoretical investigation on structure, optical response and hydrogen adsorption properties of B9/metal-B9 clusters.

DFT calculations have been carried out to shed light on the electronic structure, optical properties and hydrogen adsorption capability of neutral MB9 (where M = Li3, Na3, K3, Al, Ga, In, Rh and Co) clusters. Electronic structural studies on the parent B9(3-) clusters reveal that a less aromatic hypervalent B-centred B8 ring geometry is energetically more favoured. However, GM(3+) (Al, Ga and In) in GM@B9 prefers a highly aromatic metal-centred 9-membered molecular wheel structure. In addition, the larger size of indium breaks the D9h symmetry of the molecular wheel by coming slightly out of the ring plane unlike Al@B9 and Ga@B9. B9(n-) (n = 1-3) is also neutralized with 'n' number of Li, Na and K which revealed that AM2B9 and AM2B9(-) result in pyramidal geometries while AM3B9 results in an irregular shape by retaining the B9 framework similar to the most stable conformer of B9(3-). Metal@B9 molecular wheels show optical absorption in a broad range of the spectrum (from UV to NIR: 260-1000 nm), which is attributed to the metal's ability to perturb the ring centred excited state. Ga@B9 and Co@B9 bind with hydrogen molecules in a dissociative manner, forming two covalent bonds with peripheral B atoms of the B9 ring.

Monomerization of Homodimeric Trefoil Factor 3 (TFF3) by an Aminonitrile Compound Inhibits TFF3-Dependent Cancer Cell Survival.

Trefoil factor 3 (TFF3) is a secreted protein with an established oncogenic function and a highly significant association with clinical progression of various human malignancies. Herein, a novel small molecule that specifically targets TFF3 homodimeric functions was identified. Utilizing the concept of reversible covalent interaction, 2-amino-4-(4-(6-fluoro-5-methylpyridin-3-yl)phenyl)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile (AMPC) was identified as a molecule that interacted with TFF3. AMPC monomerized the cellular and secreted TFF3 homodimer at the cysteine (Cys)57-Cys57 residue with subsequent more rapid degradation of the generated TFF3 monomers. Hence, AMPC treatment also resulted in cellular depletion of TFF3 with consequent decreased cell viability in various human carcinoma-derived TFF3 expressing cell lines, including estrogen receptor positive (ER+) mammary carcinoma (MC). AMPC treatment of TFF3 expressing ER+ MC cells significantly suppressed total cell number in a dose-dependent manner. Consistently, exposure of TFF3 expressing ER+ MC cells to AMPC decreased soft agar colony formation, foci formation, and growth in suspension culture and inhibited growth of preformed colonies in 3D Matrigel. AMPC increased apoptosis in TFF3 expressing ER+ MC cells associated with decreased activity of EGFR, p38, STAT3, AKT, and ERK, decreased protein levels of CCND1, CCNE1, BCL2, and BCL-XL, and increased protein levels of TP53, CDKN1A, CASP7, and CASP9. siRNA-mediated depletion of TFF3 expression in ER+ MC cells efficiently abrogated AMPC-stimulated loss of cell viability and CASPASE 3/7 activities. Furthermore, in mice bearing ER+ MC cell-generated xenografts, AMPC treatment significantly impeded xenograft growth. Hence, AMPC exemplifies a novel mechanism by which small molecule drugs may inhibit a dimeric oncogenic protein and provides a strategy to impede TFF3-dependent cancer progression.

Density functional theoretical investigation of the aromatic nature of BN substituted benzene and four ring polyaromatic hydrocarbons.

We have studied the topological and local aromaticity of BN-substituted benzene, pyrene, chrysene, triphenylene and tetracene molecules. The nucleus-independent chemical shielding (NICS), harmonic oscillator model of aromaticity (HOMA), para-delocalization index (PDI) and aromatic fluctuation index (FLU) have been calculated to quantify aromaticity in terms of magnetic and structural criteria. We find that charge separations due to the introduction of heteroatoms largely affect both the local and topological aromaticity of these molecules. Our studies show that the presence of any kind of heteroatom in the ring not only reduces the local delocalization in the six membered ring, but also affects strongly the topological aromaticity. In fact, the relative orders of the topological and local aromaticity depend strongly on the position of the heteroatoms in the structure. In general, more ring shared BN containing molecules are less aromatic than the less ring shared BN molecules. In addition our results provide evidence that the structural stability of the molecule is dominated by the σ bond rather than the π bond.

Computational studies on structural and excited-state properties of modified chlorophyll f with various axial ligands.

Time-dependent density functional theory (TDDFT) calculations have been used to understand the excited-state properties of modified chlorophyll f (Chlide f), Chlide a, Chlide b, and axial ligated (with imidazole, H(2)O, CH(3)OH, CH(3)COOH, C(6)H(5)OH) Chlide f molecules. The computed differences among the Q(x), Q(y), B(x), and B(y) band absorbance wavelengths of Chlide a, b, and f molecules are found to be comparable with the experimentally observed shifts for these bands in chlorophyll a (chl a), chl b, and chl f molecules. Our computations provide evidence that the red shift in the Q(y) band of chl f is due to the extended delocalization of macrocycle chlorin ring because of the presence of the -CHO group. The local contribution from the -CHO substituent to the macrocycle chlorin ring stabilizes the corresponding molecular orbitals (lowest unoccupied molecular orbital (LUMO) of the Chlide f and LUMO-1 of the Chlide b). All the absorption bands of Chlide f shift to higher wavelengths on the addition of axial ligands. Computed redox potentials show that, among the axial ligated Chlide f molecules, Chlide f-imidazole acts as a good electron donor and Chlide f-CH(3)COOH acts as a good electron acceptor.

Influence of interface structure in redox and optical properties of thio and seleno-Ureidopeptide functionalized bimetallic gold nanocluster: DFT study.

A simple cluster-ligand interaction model is introduced to describe the surface passivation of bimetallic gold clusters by SUP (Thioureidopeptide) and SeUP (Selenoureidopeptide) ligands. The conformational search based on neutral peptide binding modes and their computed interaction energies show the existence of various structural isomers within 10 kcal mol-1. Further, the negatively charged deprotonated peptide was found to strongly interact with metal cluster through the carboxylate unit. Irrespective of the mode of binding and configuration the metal cluster found to exist in parent geometry in all three charge states. The calculated HOMO-LUMO gap of ligated clusters predicts an increase in chemical stability after the ligation. Moreover, the ligation was found to decrease the energy required for oxidation and reduction. The excited-state calculations indicate absorption maxima at 200-400 nm corresponds to the LMCT transition. In all the hybrid cluster models the donor and acceptor end of the peptide were found to remain intact. However, the charge migration dynamics observed only in the homo-metallic gold-ligand hybrids, owing to the larger charge separation.

Spectroscopic and theoretical investigation on the origin of color in jarosites.

This work aims to understand the origin of the electronic spectra of Fe3+ (d5), Cr3+ (d3), and V3+ (d2) containing jarosites. The electronic spectrum of the Fe-jarosite is currently assigned to spin forbidden transitions. This work shows that the spectra essentially arise due to the tetragonal distortion of the coordination symmetry of the Fe3+ ion in the jarosite crystal, and thereby obviates the need for invoking spin forbidden transitions. The absorption spectra of Cr- and V-jarosite are also assigned to transitions predicted for the tetragonal distortion of the metal ion coordination. The electronic term symbols are worked out using the correlation diagram and Tanabe-Sugano diagram for orbital splitting for all three systems employing ab initio and DFT methods. The bandgaps were computed and corroborated with the experimentally measured values to support the low symmetry at the metal center.

Ligand and solvation effects on the electronic properties of Au55 clusters: a density functional theory study.

The electronic properties of the neutral, positively and negatively charged bare Au(55), passivated Au(55)(PH(3))(12), Au(55)(PH(3))(12)Cl(6), and solvated Au(55)(PH(3))(12)Cl(6) 54 H(2)O clusters are studied using density functional theory. The presence of Cl atoms in the ligand shell favors a nonmetallic behavior while a more metallic behavior is induced by explicit solvation of Au(55)(PH(3))(12)Cl(6) with water molecules. The trends observed in the electronic properties upon ligation and solvation are in agreement with experimental studies.

Electronic transitions in layered hydroxides: Consequences of trigonal distortion of octahedral symmetry.

This work describes the assignment of the electronic spectra of metal ions in D3d coordination symmetry. Layered hydroxides are a class of materials that host transition metal ions such as Ni2+, Co2+, and Cr3+ in D3d coordination symmetry. The electronic spectra of these ions in the layered hydroxides exhibit significant fine structure which is assigned to transitions arising from D3d coordination symmetry. Towards this end, the correlation diagrams- complete or partial, and the resultant Tanabe-Sugano like diagrams for D3d symmetry are obtained from first principles and supported by DFT based computations. The approach engendered here helps in better understanding of the electronic transitions arising due to lower symmetry.

Computational, structural, and mechanistic analysis of the electrochemically driven pirouetting motion of a copper rotaxane.

A mechanism for the electrochemically driven reorganization of a model copper [2]pseudorotaxane is proposed on the basis of density functional theory computations and validated by comparing to experimental results. We investigate in detail the ligand reorganization around the Cu ion from a 4 to 5 coordination number that follows the conversion of the oxidation state from +1 to +2. It is found that for both the oxidation and the reduction processes the rearrangement proceeds in a concerted fashion via a single transition state. Energy paths involving stable decoordinated-coordinated intermediates are computed to be higher in energy. The cyclic voltammogram simulated using the computed transition theory state rate constants in solvent medium is in good agreement with the experimental voltammogram. Further, we report on the computed concentration change of stable (Cu(+)(4), Cu(2+)(5)) and metastable species (Cu(2+)(4), Cu(+)(5)) during single cyclic voltammetry (CV) cycle as a function of the applied voltage or time (the subscripts 4 and 5 refer to the coordination number of the copper center).