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Cisplatin is still a first-line agent in cancer treatment due to its effectiveness. Despite the large body of research concerning this drug, the role of explicit water molecules in its mechanism remains uncertain. We addressed the addition of cisplatin with the nitrogenous DNA bases adenine and guanine, with an emphasis on the impact of explicit microsolvation on every step of the action pathway of this pharmaceutical. We used electronic structure calculations to explore the energetics of the key reactions of this mechanism. We also exploited state-of-the-art methods of wave function analyses, namely, the Quantum Theory of Atoms in Molecules and the Interacting Quantum Atoms partition, to explore the chemical bonding throughout such chemical reactions. Our results reveal that microsolvation significantly differently affects electronic and Gibbs free activation energies, as previously reported (F.P. Cossio et al. ChemPhysChem, 17, 3932, 2016). The changes in activation energies are consistent with Hammond’s postulate in terms of the changes in the chemical bonding scenario between reactants and transition states. Overall, we provide an in-depth description of the importance of the surrounding water molecules of cisplatin, which aids in understanding the mechanism of pharmaceuticals in the pursuit of more effective cancer treatments.

CO2 is the most abundant greenhouse gas, and for this reason, it is the main target for finding solutions to climatic change. A strategy of environmental remediation is the transformation of CO2 to an aggregated value product to generate a carbon-neutral cycle. CO2 reduction is a great challenge because of the large C=O dissociation energy, ~179 kcal/mol. Heterogeneous photocatalysis is a strategy to address this issue, where the adsorption process is the fundamental step. The focus of this work is the role of adsorption in CO2 reduction by means of modeling the CO2 adsorption in rutile metallic oxides (TiO2, GeO2, SnO2, IrO2 and PbO2) using Density Functional Theory (DFT) and periodic DFT methods. The comparison of adsorption on different metal oxides forming the same type of crystal structure allowed us to observe the influence of the metal in the adsorption process. In the same way, we performed a comparison of the adsorption capability between two different surface planes, (001) and (110). Two CO2 configurations were observed, linear and folded: the folded conformations were observed in TiO2, GeO2 and SnO2, while the linear conformations were present in IrO2 and PbO2. The largest adsorption efficiency was displayed by the (001) surface planes. The CO2 linear and folded configurations were related to the interaction of the oxygen on the metallic surface with the adsorbate carbon, and the linear conformations were associated with the physisorption and folded configurations with chemisorption. TiO2 was the material with the best performance for CO2 interactions during the adsorption.

Background/Objectives: Chloroquine (CQ) and hydroxychloroquine (HCQ) have been the subject of debate in the treatment of COVID-19 due to the lack of conclusive evidence regarding their efficacy and safety. Our study aims to investigate the molecular interaction between the enantiomers of CQ and HCQ with angiotensin-converting enzyme 2 (ACE2), focusing on the binding mechanism, affinity, and selectivity. Methods: We used in silico methods, including molecular docking, molecular dynamics, and binding free energy calculations using the MM-PBSA method, to evaluate the interaction between the enantiomers of CQ and HCQ with ACE2. Results: We identified three main interaction sites on ACE2 (α, β, and γ) with distinct characteristics based on the pocket size, hydrophilic/hydrophobic characteristics, and affinity energy. We observed that protonation states and ionic strength significantly influence the binding affinity and specificity. In particular, the selectivity of the β-site, characterized by its smaller size and hydrophilic residues, is preferential for species with the (R) configuration, whereas the α and γ binding sites, with a larger size and amphiphilic residues, have greater affinity for the (S) enantiomer of CQ and HCQ. Furthermore, ionic strength can affect ligand binding by modulating electrostatic interactions, molecular conformation, solvation, and the stability of the complex. Conclusions: Our findings reveal that protonation states and the ionic strength substantially impact the binding affinity and specificity, regulated by spatial and polar–electrostatic complementarity, as well as hydrophobic contributions. These results suggest that understanding the interaction between CQ and HCQ enantiomers with ACE2 could be useful for the design of novel therapies against COVID-19.

Coumarin-hydroxamic acid derivatives 7a–k were herein designed with a dual purpose: as antiproliferative agents and fluorescent probes. The compounds were synthesized in moderate yields (30–87%) through a simple methodology, biological evaluation was carried out on prostate (PC3) and breast cancer (BT-474 and MDA-MB-231) cell lines to determine the effects on cell proliferation and gene expression. For compounds 7c, 7e, 7f, 7i and 7j the inhibition of cancer cell proliferation was similar to that found with the reference compound at a comparable concentration (10 μM), in addition, their molecular docking studies performed on histone deacetylases 1, 6 and 8 showed strong binding to the respective active sites. In most cases, antiproliferative activity was accompanied by greater levels of cyclin-dependent kinase inhibitor p21, downregulation of the p53 tumor suppressor gene, and regulation of cyclin D1 gene expression. We conclude that compounds 7c, 7e, 7f, 7i and 7j may be considered as potential anticancer agents, considering their antiproliferative properties, their effect on the regulation of the genes, as well as their capacity to dock to the active sites. The fluorescent properties of compound 7j and 7k suggest that they can provide further insight into the mechanism of action.

Four Metal-Organic Frameworks (MOFs) were modeled (IRMOF-C-BF2, IRMOF-C-(2)-BF2, IRMOF-C’-BF2, and IRMOF-C-CH2BF2) based on IRMOF-1. A series of linkers, based on Frustrated Lewis Pairs and coumarin moieties, were attached to IRMOF-1 to obtain MOFs with photocatalytic properties. Four different linkers were used: (a) a BF2 attached to a coumarin moiety at position 3, (b) two BF2 attached to a coumarin moiety in positions 3 and 7, (c) a BF2 attached in the coumarin moiety at position 7, and (d) a CH2BF2 attached at position 3. An analysis of the adsorption properties of H2, CO2, H2O and possible CO2 photocatalytic capabilities was performed by means of computational modeling using Density Functional Theory (DFT), Time-Dependent Density Functional (TD-DFT) methods, and periodic quantum chemical wave function approach. The results show that the proposed linkers are good enough to improve the CO2 adsorption, to hold better bulk properties, and obtain satisfactory optical properties in comparison with IRMOF-1 by itself.

Two novel BODIPY‐Ugi (boron dipyrromethene) adducts exhibit peculiar room temperature (T=20 °C) H‐1 NMR spectra in that several protons located at the aromatic aniline‐type ring are lost in the baseline. This observation revealed the existence of a dynamic conformational process where rotation around the C−N bond is hindered. Variable‐temperature H‐1 and C‐13 NMR spectroscopic analysis confirmed this conclusion; that is, low‐temperature spectra show distinct signals for all four aromatic protons below coalescence, whereas average signals are recorded above coalescence (T=+120 °C). Particularly interesting was the rather large difference in chemical shifts for the ortho protons below coalescence, Δδ=1.45 ppm, which was explained based on DFT computational analysis. Indeed, the calculated lowest‐energy gas‐phase conformation of the BODIPY Ugi adducts locates one half of the aniline‐type ring in the shielding anisotropic cone of the bridge phenyl ring in the BODIPY segment. This is in contrast to the solid‐state conformation established by X‐ray diffraction analysis that shows a nearly parallel arrangement of the aromatic rings, probably induced by crystal packing forces. A dynamic conformational process evident in two novel BODIPY‐Ugi adducts is analyzed in detail. These compounds exhibit peculiar 1H NMR spectra at room temperature, in that several protons located at the aromatic aniline‐type ring are lost in the baseline. By contrast, variable‐temperature 1H and 13C NMR‐spectroscopic analysis reveals that low‐temperature spectra exhibit distinct signals for all four aromatic protons below coalescence, while high‐temperature spectra give rise to averaged signals for all protons above coalescence.

Photocatalysis promotes eco-friendly reactions under mild conditions, and among photocatalytic agents are dyes, which have good redox potential in their excited states. The aim of the current contribution was to design a novel series of coumarins based on DFT analysis of their photochemical properties. The coumarin amide group serves as a linking group to cinnamic acid, allowing for electron delocalization throughout the system and the stabilization of the anionic and cationic species. An electronic structure analysis was performed by calculating vertical excitations and emissions, obtaining conceptual DFT chemical descriptors and nonlinear optical parameters (e.g., first static hyperpolarizability β). The novel coumarin derivatives display a reduction in the HOMO–LUMO energy gap from 6.11 to 4.2 eV, large oscillator strength (1.93), efficient nonlinear optical behavior, and excellent redox potential. Hence, they are promising compounds for photocatalytic activity. Graphical Abstract The present work shows a series of computational parameters that can be considered for the design of a molecule with potential photocatalytic activity, evaluating in this instance a series of new coumarins, promising from the computational point of view

The tautomerism of pyrimidine 2′ -deoxynucleoside, 2DN, has fundamental importance to understanding the mechanism of action in DNA replication and consequently to development of new drugs. In this work, the tautomerism of pyrimidine 2DN and some of its analogues with anticancer activity was analyzed along their potential energy surfaces by means of the MP2/cc-aug-pVDZ and QCISD/cc-aug-pVDZ theoretical methods of quantum chemistry. In gas phase and in solvent implicit (water), the energy barriers for hydrogen migration are above of 38.0 kcal/mol while tautomerization energies are between −4.9 and 10.2 kcal/mol. When hydrogen migration is catalyzed by one water molecule, the energy barriers for hydrogen migration are above of 14.2 kcal/mol, and tautomerization energies are found between 3.1 and 7.8 kcal/mol. This finding, supported by equilibrium constant and kinetic data, suggests that both tautomers, canonical and non-canonical, of each 2DN and analogues coexist in monohydrated medium forming mainly Watson–Crick pairs (WC) and some non-WC pairs. However, the calculated interaction energies of the pairs formed by guanine (G) and non-canonical pyrimidine (Pyr*) are higher than those WC pairs formed by G and Pyr, and therefore it is expected that the formation of these non-WC pairs plays an important role in the action of 2DN analogues in DNA replication.

In this work, we perform an in silico functionalization of single-wall carbon nanotubes to model the apparent solubility, binding energies and to understand the dependence of such properties on the functionalization and the electronic properties. The present study is performed using two finite models of single-wall carbon nanotubes (SWCNTs), the first one is a SWCNT with metallic character and the second one is a SWCNT with semiconductor character. In addition, we use several functionalizing molecules reported in the literature: formic acid, triethylene glycol diamine, glucosamine, polyaminobenzene sulfonic acid, and polystyrene. We found that the molecule that confers a better apparent solubility to both models of SWCNTs, metallic and semiconductor, is glucosamine, due to the several hydroxyl groups in its structure, promoting a higher polarization of the system. At the same time, we found that metallic molecules promote higher polarization compared with the nonmetallic as it is observed in the electrostatic potential surfaces. Therefore, a single-wall carbon nanotube functionalized with glucosamine is suitable to show good solubility properties that can be related to a decrease in the toxicity and an increment in the biocompatibility properties.

PurposeHistone deacetylases (HDACs) play a vital role in the epigenetic regulation of gene expression due to their overexpression in several cancer forms. Therefore, these enzymes are considered as a potential anticancer drug target. Different synthetic and natural structures have been studied as HDACs inhibitors; based on available structural design information, the capping group is important for the biological activity due to the different interactions in the active site entrance. The present study aimed to analyze high substituted pyridine as a capping group, which included carrying out the synthesis, antiproliferative activity analysis, and docking studies of these novel compounds.MethodsTo achieve the synthesis of these derivatives, four reaction steps were performed, generating desired products 15a-k. Their effects on cell proliferation and gene expression of p21, cyclin D1, and p53 were determined using the sulphorhodamine B (SRB) method and quantitative real-time polymerase chain reaction. The HDAC1, HDAC6, and HDAC8 isoforms were used for performing docking experiments with our 15a-k products.ResultThe products 15a-k were obtained in overall yields of 40–71%. Compounds 15j and 15k showed the highest antiproliferative activity in the breast (BT-474 and MDA-MB-231) and prostate (PC3) cancer cell lines at a concentration of 10 µM. These compounds increased p21 mRNA levels and decreased cyclin D1 and p53 gene expression. The docking study showed an increment in the strength, and in the number of interactions performed by the capping moiety of the tested molecules compared with SAHA; interactions displayed are mainly van der Waals, π-stacking, and hydrogen bond.ConclusionThe synthesized compounds 2-thiophene (15j) and 2-furan (15k) pyridine displayed cell growth inhibition, regulation of genes related to cell cycle progression in highly metastatic cancer cell lines. The molecular coupling analysis performed with HDAC1, HDAC6 and HDAC8 showed an increment in the number of interactions performed by the capping moiety and consequently in the strength of the capping group interaction.Graphical abstract