Consequences of the Pb-S Bond Formation for Lead Halide Perovskites.

Lead halide perovskites are structurally not stable due to their ionic bonds. Using sulfur agents in the crystal growth improves the stability and performance of the photovoltaic and light-emitting devices. In this theoretical work, we use a small toy S-radical in place of A cation in the bulk of lead iodide perovskite, and highlight the significance of the Pb-S covalent-double-bond formation for: the charge redistribution on the neighboring bonds that also turn to be covalent, phase transformation to a stable non-perovskite structure, and superior optoelectronic properties. The chemical analysis was performed with the Quantum Theory of Atoms In Molecules (QTAIM) and Non-Covalent Interactions (NCI) index. Excitonic properties were obtained from the solution of ab initio Bethe-Salpeter equation. Presence of the spin-orbit coupling triggers an interplay between the Frenkel and charge-transfer multiexcitons, switching between the photovoltaic and laser applications. Multiexcitons obey the exciton-fission preconditions.

Static and Dynamical Quantum Studies of CX3-AlX2 and CSiX3-BX2 (X = F, Cl, Br) Complexes with Hydrocyanic Acid: Unusual Behavior of Strong π-Hole at Triel Center.

The set of TX3-TrX2 (T = C, Si, Ge; Tr = B, Al, Ga; X = F, Cl, Br) molecules offers a rather unique opportunity to study both σ-hole and π-hole dimerization on the tetrel and triel ends, respectively. According to the molecular electrostatic potential (MEP) distribution, the π-hole extrema (acidic sites) were more intense than their σ-hole counterparts. The molecules owning the most (CX3-AlX2) and least (SiX3-BX2) intense π-holes were chosen to evaluate their capacities to attract one and two HCN molecules (Lewis bases). We discovered that the energetic characteristics of π-hole dimers severely conflict with the monomers MEP pattern since the weakest π-hole monomer forms a dimer characterized by interaction energy compared to those created by the monomers with noticeably greater power in the π-hole region. This outcome is due to the deformation of the weakest π-hole donor. Furthermore, the MEP analysis for monomers in the geometry of respective dimers revealed a "residual π-hole" site that was able to drive second ligand attachment, giving rise to the two "unusual trimers" examined further by the NCI and QTAIM analyses. Apart from them, the π-hole/π-hole and σ-hole/π-hole trimers have also been obtained throughout this study and described using energetic and geometric parameters. The SAPT approach revealed details of the bonding in one of the "unusual trimers". Finally, Born-Oppenheimer Molecular Dynamics (BOMD) simulations were carried out to investigate the time evolution of the interatomic distances of the studied complexes as well as their stability.

Affinities to Oxaliplatin: Vitamins from B Group vs. Nucleobases.

Oxaliplatin, similar to Cisplatin, exhibits anticancer activity by interacting with DNA and inducing programmed cell death. It is biotransformed through a number of spontaneous and non-enzymatic processes. In this way, several transient reactive species are formed, including dichloro-, monochloro-, and diaqua-DACH platin, which can complex with DNA and other macromolecules. The molecular level suggests that such interactions can also take place with vitamins containing aromatic rings with lone pair orbitals. Theoretical and experimental studies were performed to investigate interactions of vitamins from the B group with Oxaliplatin, and the results were compared with values characterizing native purines. Quantum-chemical simulations were carried out at the B3LYP/6-31G(d,p) level, with the LANL2DZ basis set representing atomic orbitals of platinum atom, and at the MN15/def2-TZVP levels of theory with the use of Polarizable Continuum Model (IEF-PCM formulation) and water as a solvent. Additionally, time-dependent density functional theory (TD-DFT) was employed to study molecular properties in the electronic excited state. Interactions of vitamins and Oxaliplatin were investigated using UV-Vis spectroscopy. Values of the free energy (ΔGr) indicate spontaneous reactions with monoaqua [PtH2OClDACH]+ and diaqua [Pt(H2O)2DACH]2+ derivatives of Oxaliplatin. However, diaqua derivatives were found to be preferable. The free energy (ΔGr) values obtained for vitamins from the B group indicate lower affinity of Oxaliplatin compared with values characterizing complexes formed by guanine, adenine, and cytosine. The exception is the monoaqua form of vitamin B1 (thiamine) at the MN15/def2-TZVP levels of calculations. An application of atoms in molecules (AIM) theory revealed non-covalent interactions present in the complexes studied. The comparison of computed and experimental spectroscopic properties showed a good agreement.

Chalcogen Bond as a Factor Stabilizing Ligand Conformation in the Binding Pocket of Carbonic Anhydrase IX Receptor Mimic.

It is postulated that the overexpression of Carbonic Anhydrase isozyme IX in some cancers contributes to the acidification of the extracellular matrix. It was proved that this promotes the growth and metastasis of the tumor. These observations have made Carbonic Anhydrase IX an attractive drug target. In the light of the findings and importance of the glycoprotein in the cancer treatment, we have employed quantum-chemical approaches to study non-covalent interactions in the binding pocket. As a ligand, the acetazolamide (AZM) molecule was chosen, being known as a potential inhibitor exhibiting anticancer properties. First-Principles Molecular Dynamics was performed to study the chalcogen and other non-covalent interactions in the AZM ligand and its complexes with amino acids forming the binding site. Based on Density Functional Theory (DFT) and post-Hartree-Fock methods, the metric and electronic structure parameters were described. The Non-Covalent Interaction (NCI) index and Atoms in Molecules (AIM) methods were applied for qualitative/quantitative analyses of the non-covalent interactions. Finally, the AZM-binding pocket interaction energy decomposition was carried out. Chalcogen bonding in the AZM molecule is an important factor stabilizing the preferred conformation. Free energy mapping via metadynamics and Path Integral molecular dynamics confirmed the significance of the chalcogen bond in structuring the conformational flexibility of the systems. The developed models are useful in the design of new inhibitors with desired pharmacological properties.

Biological Evaluation and Molecular Docking Studies of Novel 1,3,4-Oxadiazole Derivatives of 4,6-Dimethyl-2-sulfanylpyridine-3-carboxamide.

To date, chronic inflammation is involved in most main human pathologies such as cancer, and autoimmune, cardiovascular or neurodegenerative disorders. Studies suggest that different prostanoids, especially prostaglandin E2, and their own synthase (cyclooxygenase enzyme-COX) can promote tumor growth by activating signaling pathways which control cell proliferation, migration, apoptosis, and angiogenesis. Non-steroidal anti-inflammatory drugs (NSAIDs) are used, alongside corticosteroids, to treat inflammatory symptoms particularly in all chronic diseases. However, their toxicity from COX inhibition and the suppression of physiologically important prostaglandins limits their use. Therefore, in continuation of our efforts in the development of potent, safe, non-toxic chemopreventive compounds, we report herein the design, synthesis, biological evaluation of new series of Schiff base-type hybrid compounds containing differently substituted N-acyl hydrazone moieties, 1,3,4-oxadiazole ring, and 4,6-dimethylpyridine core. The anti-COX-1/COX-2, antioxidant and anticancer activities were studied. Schiff base 13, containing 2-bromobenzylidene residue inhibited the activity of both isoenzymes, COX-1 and COX-2 at a lower concentration than standard drugs, and its COX-2/COX-1 selectivity ratio was similar to meloxicam. Furthermore, the results of cytotoxicity assay indicated that all of the tested compounds exhibited potent anti-cancer activity against A549, MCF-7, LoVo, and LoVo/Dx cell lines, compared with piroxicam and meloxicam. Moreover, our experimental study was supported by density functional theory (DFT) and molecular docking to describe the binding mode of new structures to cyclooxygenase.

Synthesis, Anticancer Activity and Molecular Docking Studies of Novel N-Mannich Bases of 1,3,4-Oxadiazole Based on 4,6-Dimethylpyridine Scaffold.

Cancer is one of the greatest challenges in modern medicine today. Difficult and long-term treatment, the many side effects of the drugs used and the growing resistance to treatment of neoplastic cells necessitate new approaches to therapy. A very promising targeted therapy is based on direct impact only on cancer cells. As a continuation of our research on new biologically active molecules, we report herein the design, synthesis and anticancer evaluation of a new series of N-Mannich-base-type hybrid compounds containing morfoline or different substituted piperazines moieties, a 1,3,4-oxadiazole ring and a 4,6-dimethylpyridine core. All compounds were tested for their potential cytotoxicity against five human cancer cell lines, A375, C32, SNB-19, MCF-7/WT and MCF-7/DX. Two of the active N-Mannich bases (compounds 5 and 6) were further evaluated for growth inhibition effects in melanoma (A375 and C32), and normal (HaCaT) cell lines using clonogenic assay and a population doubling time test. The apoptosis was determined with the neutral version of comet assay. The confocal microscopy method enabled the visualization of F-actin reorganization. The obtained results demonstrated that compounds 5 and 6 have cytotoxic and proapoptotic effects on melanoma cells and are capable of inducing F-actin depolarization in a dose-dependent manner. Moreover, computational chemistry approaches, molecular docking and electrostatic potential were employed to study non-covalent interactions of the investigated compounds with four receptors. It was found that all the examined molecules exhibit a similar binding affinity with respect to the chosen reference drugs.

Exploring the Dynamical Nature of Intermolecular Hydrogen Bonds in Benzamide, Quinoline and Benzoic Acid Derivatives.

The hydrogen bonds properties of 2,6-difluorobenzamide, 5-hydroxyquinoline and 4-hydroxybenzoic acid were investigated by Car-Parrinello and path integral molecular dynamics (CPMD and PIMD), respectively. The computations were carried out in vacuo and in the crystalline phase. The studied complexes possess diverse networks of intermolecular hydrogen bonds (N-H…O, O-H…N and O-H…O). The time evolution of hydrogen bridges gave a deeper insight into bonds dynamics, showing that bridged protons are mostly localized on the donor side; however, the proton transfer phenomenon was registered as well. The vibrational features associated with O-H and N-H stretching were analyzed on the basis of the Fourier transform of the atomic velocity autocorrelation function. The spectroscopic effects of hydrogen bond formation were studied. The PIMD revealed quantum effects influencing the hydrogen bridges providing more accurate free energy sampling. It was found that the N…O or O…O interatomic distances decreased (reducing the length of the hydrogen bridge), while the O-H or N-H covalent bond was elongated, which led to the increase in the proton sharing. Furthermore, Quantum Theory of Atoms in Molecules (QTAIM) was used to give insight into electronic structure parameters. Finally, Symmetry-Adapted Perturbation Theory (SAPT) was employed to estimate the energy contributions to the interaction energy of the selected dimers.

Revealing Intra- and Intermolecular Interactions Determining Physico-Chemical Features of Selected Quinolone Carboxylic Acid Derivatives.

The intra- and intermolecular interactions of selected quinolone carboxylic acid derivatives were studied in monomers, dimers and crystals. The investigated compounds are well-recognized as medicines or as bases for further studies in drug design. We employed density functional theory (DFT) in its classical formulation to develop gas-phase and solvent reaction field (PCM) models describing geometric, energetic and electronic structure parameters for monomers and dimers. The electronic structure was investigated based on the atoms in molecules (AIM) and natural bond orbital (NBO) theories. Special attention was devoted to the intramolecular hydrogen bonds (HB) present in the investigated compounds. The characterization of energy components was performed using symmetry-adapted perturbation theory (SAPT). Finally, the time-evolution methods of Car-Parrinello molecular dynamics (CPMD) and path integral molecular dynamics (PIMD) were employed to describe the hydrogen bond dynamics as well as the spectroscopic signatures. The vibrational features of the O-H stretching were studied using Fourier transformation of the autocorrelation function of atomic velocity. The inclusion of quantum nuclear effects provided an accurate depiction of the bridged proton delocalization. The CPMD and PIMD simulations were carried out in the gas and crystalline phases. It was found that the polar environment enhances the strength of the intramolecular hydrogen bonds. The SAPT analysis revealed that the dispersive forces are decisive factors in the intermolecular interactions. In the electronic ground state, the proton-transfer phenomena are not favourable. The CPMD results showed generally that the bridged proton is localized at the donor side, with possible proton-sharing events in the solid-phase simulation of stronger hydrogen bridges. However, the PIMD enabled the quantitative estimation of the quantum effects inclusion-the proton position was moved towards the bridge midpoint, but no qualitative changes were detected. It was found that the interatomic distance between the donor and acceptor atoms was shortened and that the bridged proton was strongly delocalized.

Effect of Copper(II) Ion Binding by Porin P1 Precursor Fragments from Fusobacterium nucleatum on DNA Degradation.

Fusobacterium nucleatum is one of the most notorious species involved in colorectal cancer. It was reported that numerous outer membrane proteins (OMP) are actively involved in carcinogenesis. In this paper, the structure and stability of certain complexes, as well as DNA cleavage and ROS generation by fragments of OMP, were investigated using experimental and theoretical methods. Mass spectrometry, potentiometry, UV-Vis, CD, EPR, gel electrophoresis and calculations at the density functional theory (DFT) level were applied. Two consecutive model peptides, Ac-AKGHEHQLE-NH2 and Ac-FGEHEHGRD-NH2, were studied. Both of these were rendered to form a variety of thermodynamically stable complexes with copper(II) ions. All of the complexes were stabilized, mainly due to interactions of metal with nitrogen and oxygen donor atoms, as well as rich hydrogen bond networks. It was also concluded that these complexes in the presence of hydrogen peroxide or ascorbic acid can effectively produce hydroxyl radicals and have an ability to cleave the DNA strands. Surprisingly, the second studied ligand at the micromolar concentration range causes overall DNA degradation.

Photochemical Transformations of Peptides Containing the N-(2-Selenoethyl)glycine Moiety.

The diselenide bond has attracted considerable attention due to its ability to undergo the metathesis reaction in response to visible light. In our previous study, we demonstrated visible-light-induced diselenide metathesis of selenocysteine-containing linear peptides, allowing for the convenient generation of peptide libraries. Here, we investigated the transformation of linear and cyclic peptides containing the N-(2-selenoethyl)glycine moiety. The linear peptides were highly susceptible to the metathesis reaction, whereas the cyclic systems gave only limited conversion yields of the metathesis product. In both cases, side reactions leading to the formation of mono-, di-, and polyselenides were observed upon prolonged irradiation. To confirm the radical mechanism of the reaction, the radical initiator 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (VA-044) was tested, and it was found to induce diselenide metathesis without photochemical activation. The data were interpreted in the light of quantum-chemical simulations based on density functional theory (DFT). The simulations were performed at the B3LYP-D3BJ/def2-TZVP level of theory using a continuum solvation model (IEF-PCM) and methanol as a solvent.

Role of Non-Covalent Interactions in Carbonic Anhydrase I-Topiramate Complex Based on QM/MM Approach.

Carbonic anhydrase (CA) I with a Topiramate (TPM) complex was investigated on the basis of a Quantum Mechanics/Molecular Mechanics (QM/MM) approach. The QM part was treated using Density Functional Theory (DFT) while the MM was simulated using Amberff14SB and GAFF force fields. In addition, the TIP3P model was applied to reproduce the polar environment influence on the studied complex. Next, three snapshots (after 5 ps, 10 ps, and 15 ps of the simulation time) were taken from the obtained trajectory to provide an insight into the non-covalent interactions present between the ligand and binding pocket of the protein. Our special attention was devoted to the binding site rearrangement, which is known in the literature concerning the complex. This part of the computations was performed using ωB97X functional with Grimme D3 dispersion corrections as well as a Becke-Johnson damping function (D3-BJ). Two basis sets were applied: def2-SVP (for larger models) and def2-TZVPD (for smaller models), respectively. In order to detect and describe non-covalent interactions between amino acids of the binding pocket and the ligand, Independent Gradient Model based on Hirshfeld partitioning (IGMH), Interaction Region Indicator (IRI), Quantum Theory of Atoms in Molecules (QTAIM) and Natural Bond Orbitals (NBO) methods were employed. Finally, Symmetry-Adapted Perturbation Theory (SAPT) was applied for energy decomposition between the ligand and protein. It was found that during the simulation time, the ligand position in the binding site was preserved. Nonetheless, amino acids interacting with TPM were exchanging during the simulation, thus showing the binding site reorganization. The energy partitioning revealed that dispersion and electrostatics are decisive factors that are responsible for the complex stability.

Fusobacterium nucleatum - Friend or foe?

Fusobacterium nucleatum (F. nucleatum) is one of the most abundant Gram-negative anaerobic bacteria, part of the gut, and oral commensal flora, generally found in human dental plaque. Its presence could be associated with various human diseases, including, e.g., periodontal, angina, lung and gynecological abscesses. This bacteria can enter the blood circulation as a result of periodontal infection. It was proven that F. nucleatum migrates from its primary site of colonization in the oral cavity to other parts of the body. It could cause numerous diseases, including cancers. On the other hand, it was shown that Fusobacterium produces significant amounts of butyric acid, which is a great source of energy for colonocytes (anti-inflammatory cells). Therefore, it is very interesting to get to know the two faces of F. nucleatum.