It is shown that the response of molecular properties of diatomics such as the total energy, the bond length, and the vibrational Stark shift to an external homogenous electric field (EF) can be predicted from field-free observable properties such as the equilibrium bond length, the bond dissociation energy, the polarizability and dipole moment functions, and the vibrational frequency. Delley [J. Mol. Struct.: THEOCHEM 434, 229 (1998)] suggested to approximate the potential energy surface under an EF by a Morse function augmented with a EF term proportional to the internuclear separation. In this work, this term is replaced by the expression of the field-induced energy change which yields a field-perturbed Morse potential that tends to a constant asymptotic limit when the EF term itself become proportional to the sum of the polarizabilities of the separated atoms. The model is validated by comparison with direct calculations on nine diatomics, five homo-nuclear (H2, N2, O2, F2, and Cl2) and four hetero-nuclear (HF, HCl, CO, and NO), covering a range and combinations of dipole moments and polarizabilities. Calculations were conducted at the quadratic configuration interaction with single and double excitations (QCISD) and density functional theory (DFT)-B3LYP levels of theory using the 6-311++G(3df,2pd) basis set. All results agree closely at the two levels of theory except for the Stark effect of NO which is not correctly predicted by QCISD calculations as further calculations, including at the coupled cluster with single and double excitation (CCSD) level of theory, demonstrate.

Sulfur tetrafluoride was shown to act as a Lewis acid towards organic nitrogen bases, such as pyridine, 2,6-dimethylpyridine, 4-methylpyridine, and 4-dimethylaminopyridine. The SF4 ⋅NC5 H5 , SF4 ⋅2,6-NC5 H3 (CH3 )2 , SF4 ⋅4-NC5 H4 (CH3 ), and SF4 ⋅4-NC5 H4 N(CH3 )2 adducts can be isolated as solids that are stable below -45 °C. The Lewis acid-base adducts were characterized by low-temperature Raman spectroscopy and the vibrational bands were fully assigned with the aid of density functional theory (DFT) calculations. The electronic structures obtained from the DFT calculations were analyzed by the quantum theory of atoms in molecules (QTAIM). The crystal structures of SF4 ⋅NC5 H5 , SF4 ⋅4-NC5 H4 (CH3 ), and SF4 ⋅4-NC5 H4 N(CH3 )2 revealed weak SN dative bonds with nitrogen coordinating in the equatorial position of SF4 . Based on the QTAIM analysis, the non-bonded valence shell charge concentration on sulfur, which represents the lone pair, is only slightly distorted by the weak dative SN bond. No evidence for adducts between quinoline or isoquinoline with SF4 was found by low-temperature Raman spectroscopy.

Necroptosis is a form of regulated cell death which results in loss of plasma membrane integrity, release of intracellular contents, and an associated inflammatory response. We previously found that saturated very long chain fatty acids (VLCFAs), which contain ≥20 carbons, accumulate during necroptosis. Here, we show that genetic knockdown of Fatty Acid (FA) Elongase 7 (ELOVL7) reduces accumulation of specific very long chain FAs during necroptosis, resulting in reduced necroptotic cell death and membrane permeabilization. Conversely, increasing the expression of ELOVL7 increases very long chain fatty acids and membrane permeabilization. In vitro, introduction of the VLCFA C24 FA disrupts bilayer integrity in liposomes to a greater extent than a conventional C16 FA. To investigate the microscopic origin of these observations, atomistic Molecular Dynamics (MD) simulations were performed. MD simulations suggest that fatty acids cause clear differences in bilayers based on length and that it is the interdigitation of C24 FA between the individual leaflets that results in disorder in the region and, consequently, membrane disruption. We synthesized clickable VLCFA analogs and observed that many proteins were acylated by VLCFAs during necroptosis. Taken together, these results confirm the active role of VLCFAs during necroptosis and point to multiple potential mechanisms of membrane disruption including direct permeabilization via bilayer disruption and permeabilization by targeting of proteins to cellular membranes by fatty acylation.

Quantum mechanical methods are used to investigate the chemical steps during the bifunctional (glycosylase and β-lyase) activity of bacterial FPG DNA glycosylase, which removes the major oxidation product (8-oxoguanine) from DNA as part of the base excision repair process. To facilitate investigation of all potential pathways, the smallest chemically relevant model is implemented, namely a modified OG nucleoside-3'-monophosphate and a truncated proline nucleophile. Potential energy surfaces are characterized with SMD-M06-2X/6-311+G(2df,2p)//PCM-B3LYP/6-31G(d) and compared to a previous study on the analogues human enzyme (hOgg1), which uses a lysine nucleophile (Kellie, J. L.; Wetmore, S. D. J. Phys. Chem. B 2012, 116, 10786-10797). Our large calculated barriers indicate that FPG must actively catalyze the three main phases of the overall reaction, namely, deglycosylation, (deoxyribose) ring-opening, and β-elimination, and provide clues about how this is achieved through comparison to accurate crystal structures. The main conclusions about key mechanistic steps hold true regardless of the nucleophile, suggesting that most major differences in the relative activity of FPG and hOgg1 are primarily due to other active site residues. Nevertheless, support for possible monofunctional (deglycosylation only) activity is only evident when lysine is the nucleophile. This finding agrees with experimental observations of monofunctional activity of hOgg1 and further supports the broadly accepted bifunctional activity of FPG.

An improved and scalable synthesis of the unsubstituted 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene framework facilitates access to the previously unreported parent dipyrrin HCl salt, as well as 4,4-dichloro-4-bora-3a,4a-diaza-s-indacene.

Polyhexamethylene biguanide (PHMB) is a cationic polymer with antimicrobial and antiviral properties. It has been commonly accepted that the antimicrobial activity is due the ability of PHMB to perforate the bacterial phospholipid membrane leading ultimately to its death. In this study we show by the means of atomistic molecular dynamics (MD) simulations that while the PHMB molecules attach to the surface of the phospholipid bilayer and partially penetrate it, they do not cause any pore formation at least within the microsecond simulation times. The polymers initially adsorb onto the membrane surface via the favourable electrostatic interactions between the phospholipid headgroups and the biguanide groups, and then partially penetrate the membrane slightly disrupting its structure. This, however, does not lead to the formation of any pores. The microsecond-scale simulations reveal that it is unlikely for PHMB to spontaneously pass through the phospholipid membrane. Our findings suggest that PHMB translocation across the bilayer may take place through binding to the phospholipids. Once inside the cell, the polymer can effectively 'bind' to DNA through extensive interactions with DNA phosphate backbone, which can potentially block the DNA replication process or activate DNA repair pathways.

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Oriented external electric fields (OEEFs) have been shown to have great potential in being able to provide unprecedented control of chemical reactions, catalysis, and selectivity with applications ranging from H 2 storage to molecular machines. We report a theoretical study of the atomic origins of molecular changes because of OEEFs since understanding the characteristics of OEEF-induced couplings between atomic and molecular properties is an important step toward comprehensive understanding of the effects of strong external fields on the molecular structure, stability, and reactivity. We focus on the atomic and molecular (bond) properties of a set of homo-(H 2 , N 2 , O 2 , F 2 , and Cl 2 ) and heterodiatomic (HF, HCl, CO, and NO) molecules under intense external electric fields in the context of quantum theory of atoms in molecules (QTAIM). It is shown that the atomic properties (atomic charges, energies, and localization indices) correlate linearly with the field strengths, but molecular properties (bond length, electron density at the bond critical point, and electron delocalization index) exhibit nonlinear responses to the imposed fields. In particular, the changes in the electron density distribution alter the shapes and locations of the zero-flux surfaces, atomic volumes, atomic electron population, and localization/ delocalization indices. The topography and topology of the molecular electrostatic potential undergo dramatic changes. External fields also perturb the covalent−polar−ionic characteristic of the studied chemical bonds, hallmarking the impact of electric fields on the stability and reactivity of chemical compounds. The findings are well-rationalized within the framework of the QTAIM and form a coherent conceptual understanding of these effects in prototypical diatomic molecules.