A theoretical study on radical scavenging activity of phenolic derivatives naturally found within Alternaria alternata extract.

The increasing oxidative stress demands potential chemical compounds derived from natural resources with good antioxidant activity to overcome adverse health issues. In this context, we investigated the antioxidant properties of four dibenzopyrone phenolic compounds obtained from the endophytic fungus Alternaria alternata: altenusin, altenusin B, alterlactone, and dehydroaltenusin using DFT calculations. Our investigation focused on understanding the structure-antioxidant property relationship. It delved into probing the activity by modelling the antioxidant mechanisms. The computed transition states and thermochemical parameters, along with the structural attributes, indicate that altenusin B has good antioxidant efficacy among the four compounds, and it follows the HAT mechanism in an aqueous phase. Remarkably, our findings indicate that altenusin B exhibits potent HOO˙ radical scavenging properties, characterized by the computed high rate constant. The molecular docking studies of these compounds with the pro-oxidant enzyme xanthine oxidase (XO) gave insights into the binding modes of the compounds in the protein environment. Furthermore, molecular dynamics (MD) simulations were employed to study the interaction and stability of the compounds inside the XO enzyme. Our exploration sheds light on the radical scavenging potential of the -OH sites and the underlying antioxidant mechanisms that underpin the compounds' effective antioxidant potential.

Why trans and not cis? - Molecular dynamics and DFT study on selective separation of dihaloethene isomers using perethylated pillar[5]arene.

The separation of mixtures of isomers is a daunting task. It is found that perethylated pillar[5]arene can separate trans-dichloroethene from its cis isomer. This work deals with the host-guest interactions and the selective separation of trans dihaloethene over cis-dihaloethene using perethylated pillar[5]arene. From this work, one can understand why only trans dihaloethenes are encapsulated while cis-dihaloethenes are not. Initially, molecular dynamics was performed at different picoseconds for the 1 : 1 inclusion complexes. In addition to these, MD simulation on a mixture of cis & trans isomers has also been done to ensure the preferential selectivity of perethylated pillar[5]arene towards the trans isomer. A brief DFT study was carried out to explain the better encapsulation of trans-dihaloethene in perethylated pillar[5]arene. Frontier molecular orbital analysis provides information on the stability and reactivity of the dihaloethene isomers. The non-covalent interactions between the host and the guest are determined using the quantum theory of atoms in molecules. Energy decomposition analysis indicates that the solvent phase influences the binding energy to a greater extent compared to the gas phase and orbital interaction energies are reduced substantially upon moving from the gas to the solvent phase. The Gibbs free energy indicates that these isomers readily form inclusion complexes with perethylated pillar[5]arene. Overall our results provide valuable information on the non-covalent interactions that drive the inclusion phenomenon in these host-guest systems.

A two-step MM and QM/MM approach to model AIEE of aryloxy benzothiadiazole derivatives for optoelectronic applications.

Aryloxy-benzothiadiazole (ArO-Btz) derivatives show aggregation-induced enhanced emission (AIEE) in the solid-state and are promising candidates for optoelectronic applications. However, understanding the AIEE is a challenging task and is necessary for the rational molecular design of emitters. Therefore, in the present study, electron acceptors (-F, -CN, -NO2, and -COOH) on the benzothiadiazole ring have been screened for emission in solution and aggregated phases. Herein, we report QM (DFT/TDDFT) and ONIOM (QM/MM) studies on the four ArO-Btz derivatives in comparison with the parent molecule with typical characteristics of AIEE, optoelectronic and non-linear optical properties. Starting from the optimized crystal structure of the parent compound, the structures of the designed clusters have been pre-optimized with MM and then with QM/MM to explore their absorption and emission in the solid phase. The results indicate that in the aggregated phase, the surrounding environment reduces intra-molecular rotations and molecular motion that lead to enhanced emission. Natural bond orbital (NBO) analyses reveal that the ground state structure is stabilized from electron delocalization and operative push-pull effects. Interestingly, nitro-benzothiadiazole exhibits prominent AIEE phenomena, with an emission wavelength beyond 700 nm in solution and in the cluster, reinforced by the magnification of its oscillatory strength by 100 times when aggregated. This dinitro-aryloxy-benzothiadiazole derivative is proposed as a near-infrared emitter for dye-sensitized solar cell, optoelectronic, and non-linear optical applications.

Bioactive platinum complex of ligand bearing pyrimidine skeleton: DNA/BSA binding, molecular docking, anticancer, antioxidant and antimicrobial activities.

A new octahedral platinum complex [PtLCl4] of Schiff base ligand containing pyrimidine and morpholine skeleton (where, L is 4,6-dichloropyrimidin-5-yl)methylene)-2-morpholinoethanamine) was isolated and characterized by elemental analysis, 1H-NMR, FTIR, UV-visible and ESI-MS techniques. DNA interaction of isolated compounds with calf thymus (CT-DNA) was explored by UV-vis absorption, fluorescence, cyclic voltametric and viscometric methods. The result shows that prepared compounds can interact with CT-DNA through electrostatic interactions. Bovine serum album (BSA) binding behavior of isolated compounds was also studied by UV-vis absorption and fluorescence techniques. Both the spectroscopic results suggest that the isolated ligand and its complex bind with BSA through static quenching. The optimized structure of ligand and platinum complex were achieved by the DFT calculations. Moreover, molecular docking of ligand and its complex were studied. These analysis results reveal that ligand has low binding affinity on DNA and BSA molecules in contrast to its complex. In vitro anticancer activity of isolated compounds toward normal cell line (NHDF) as well as cancer cell lines (MCF-7, HepG2, HeLa and A549) was studied by MTT assay. The results supports that isolated platinum complex can control the growth of cancer cells (MCF-7, 20.12 ± 1.00 µg/mL; HepG2, 32.2 ± 1.69 µg/mL; HeLa, 24.68 ± 1.29 µg/mL; A549, 23.46 ± 1.17 µg/mL) without inhibiting the normal cell line (NHDF, 109.26 ± 5.46 µg/mL). Antioxidant and antimicrobial activities of isolated compounds indicate that ligand and Pt complex are found to have good radical scavenging against four different free radicals and antimicrobial abilities on E. coli and C. albicans antimicrobial species. HighlightsPlatinum complex of Schiff base with pyrimidine and morpholine linkage was synthesized.Pt complex has better biomolecular interaction with DNA and BSA.Molecular docking of Pt complex with DNA and BSA has been studiedPt complex has good anticancer activities.Pt complex has better antioxidant and antimicrobial activities.

Platinum complex with pyrimidine- and morpholine-based ligand: synthesis, spectroscopic, DFT, TDDFT, catalytic reduction, in vitro anticancer, antioxidant, antimicrobial, DNA binding and molecular modeling studies.

New monometallic platinum complex ([PtL2Cl2]Cl2) of pyrimidine and morpholine derivative ligand were synthesized and structurally elucidated by elemental analysis, molar conductance, 1H NMR, FT-IR, ESI-MS and UV-Visible spectroscopic techniques. Analytical and spectroscopic result suggests that platinum complex has octahedral geometry. In order to understand the molecular geometry and absorption spectra of the ligand and platinum complex, DFT and TDDFT calculations have been carried out. Catalytic reduction of platinum complex with p-nitrophenol (p-NP) was carried out by the spectrophotometric method. In vitro anticancer activity of ligand and platinum complex on human cancer cell lines (MCF-7, HepG2, HeLa and A549) as well as normal cell (NHDF) line was done by MTT assay. This result reveals that platinum complex has enhanced anticancer against MCF-7 (19.13 ± 0.96 µg/mL) cell line than HepG2 (32.82 ± 1.64 µg/mL), HeLa (29.2 ± 1.46 µg/mL) and A549 (34.21 ± 1.71, µg/mL) cell lines as compared to ligand. Antioxidant activity results sustained that platinum complex has better radical scavenging ability than ligand. Platinum complex has better antimicrobial activity toward E. coli bacteria and C. albicans fungi than other antimicrobial pathogens. DNA binding affinities of the ligand and platinum complex have been assessed by probing their ability to bind to calf thymus DNA (CT-DNA) with UV-Visible, fluorescence, viscometric measurements and cyclic voltammetric techniques. These results proved that ligand and platinum bind to CT-DNA by intercalative binding mode. Molecular docking analysis reveals that the platinum complex tends to show good binding affinity toward both DNA and BSA than ligand.

Impacts of hydrophobicity and ionicity of phendione-based cobalt(II)/(III) complexes on binding with bovine serum albumin.

For efficient designing of metallodrugs, it is imperative to analyse the binding affinity of those drugs with drug-carrying serum albumins to comprehend their structure-activity correlation for biomedical applications. Here, cobalt(II) and cobalt(III) complexes comprising three phendione ligands, [Co(phendione)3]Cl2 (1) and [Co(phendione)3]Cl3 (2), where, phendione = 1,10-phenanthroline-5,6-dione, has been chosen to contrast the impact of their hydrophobicity and ionicity on binding with bovine serum albumin (BSA) through spectrophotometric titrations. The attained hydrophobicity values using octanol/water partition coefficient method manifested that complex 1 is more hydrophobic than complex 2, which could be attributed to lesser charge on its coordination sphere. The interaction of complexes 1 and 2 with BSA using steady state fluorescence studies revealed that these complexes quench the intrinsic fluorescence of BSA through static mechanism, and the extent of quenching and binding parameters are higher for complex 2. Further thermodynamics of BSA-binding studies revealed that complexes 1 and 2 interact with BSA through hydrophobic and hydrogen bonding/van der Waals interactions, respectively. Further, UV-visible absorption, circular dichroism and synchronous fluorescence studies confirmed the occurrence of conformational and microenvironmental changes in BSA upon binding with complexes 1 and 2. Molecular docking studies have also shown that complex 2 has a higher binding affinity towards BSA as compared to complex 1. This sort of modification of ionicity and hydrophobicity of metal complexes for getting desirable binding mode/strength with drug transporting serum albumins will be a promising pathway for designing active and new kind of metallodrugs for various biomedical applications.Communicated by Ramaswamy H. Sarma.

Density functional theory molecular modelling, DNA interactions, antioxidant, antimicrobial, anticancer and biothermodynamic studies of bioactive water soluble mixed ligand complexes.

A novel series of bioactive water soluble mixed ligand complexes (1-5) [MII(L)(phen)AcO]. nH2O {where M = Cu (1) n = 2; Co (2), Mn (3), Ni (4), n = 4 and Zn (5) n = 2} were synthesized from 2-(2-Morpholinoethylimino) methyl)phenol Schiff base ligand (LH), 1, 10-phenanthroline and metal(II) acetate salt in a 1:1:1 stoichiometric ratio and characterized by several spectral techniques. The obtained analytical and spectral data suggest the octahedral geometry around the central metal ion. Density functional theory calculations have been further supportive to explore the optimized structure and chemical reactivity of these complexes from their frontier molecular orbitals. Gel electrophoresis result indicates that complex (1) manifested an excellent DNA cleavage property than others. The observed binding constants with free energy changes by electronic absorption technique and DNA binding affinity values by viscosity measurements for all compounds were found in the following order (1) > (2) > (4) > (5) > (3) > (LH). The binding results and thermodynamic parameters are described the intercalation mode. In vitro antioxidant properties disclose that complex (1) divulges high scavenging activity against DPPH•, •OH, O2-• NO•, and Fe3+. The antimicrobial reports illustrate that the complexes (1-5) were exhibited well defined inhibitory effect than ligand (LH) against the selected different pathogenic species. The observed percentage growth inhibition against A549, HepG2, MCF-7, and NHDF cell lines suggest that complex (1) has exhibited superior anticancer potency than others. Thus, the complex (1) may contribute as potential anticancer agent due to its unique interaction mode with DNA.GRAPHICAL ABSTRACT Communicated by Ramaswamy H. Sarma.

A new turn in codon-anticodon selection through halogen bonds.

The halogen bond is relatively a less characterized intermolecular interaction compared to the hydrogen bond and the structure, stability and electronic structures of halogenated base pairs, particularly at the wobble junction have been investigated using DFT. Three halogens, namely Cl, Br and I, have been tested for their role in such situations with uracil as the anticodon base. Computed results reveal that when halogen atoms replace protons in the hydrogen bonding positions they induce lot of geometric changes that flip some of the observed base pairs into unobserved base pairs and vice versa. NCI, NBO and AIM analyses explain these changes at the electronic level. The new codons will have lot of impact in future applications, particularly in self assembly of biomaterials and t-RNA synthetic strategies.