Increasing the utility of epidemiologic studies as key evidence in chemical risk assessment.

The Society of Toxicology 2024 meeting assembled risk assessors, epidemiologists, and toxicologists to discuss the utility of integrating epidemiologic data into the derivation of reference values. Advantages of the use of epidemiologic evidence include (i) human relevance; (ii) increased likelihood that exposure levels are relevant to risk assessment; and (iii) incorporation of uncertainties attributed to co-exposures or other population-based considerations. The workshop panelists discussed the challenges of incorporating epidemiologic evidence due to uncertain exposure measurements, confounding, heterogeneity, and inherent study design limitations.

Ring Size Effects on the Structures of Sandwich Compounds with a Stoichiometry of CHM (M = Ti-Ni).

Ring size effects on geometries and electronic structures were investigated for the (C H )M(C H ) ( = 4, 5, or 6; = 8, 7, or 6; + = 12; M = Ti-Ni) systems using density functional theory. The lowest-energy CHM structures for the early transition metals titanium, vanadium, and chromium are the experimentally known singlet (η-CH)Ti(η-CH), doublet (η-CH)V(η-CH), and singlet (η-CH)Cr, respectively. The likewise experimentally known singlet (η-CH)Ti, doublet (η-CH)V, and singlet (η-CH)Cr(η-CH) are the second-lowest-energy structures with only a small energy difference between the two vanadium structures.

Evaluating the Importance of Conformers for Understanding the Vacuum-Ultraviolet Spectra of Oxiranes: Experiment and Theory.

Vacuum-ultraviolet (VUV) absorption spectroscopy enables electronic transitions that offer the unambiguous identification of molecules. As target molecules become more complex, multifunctional species present a great challenge to both experimental and computational spectroscopy. This research reports both experimental and theoretical studies of oxiranes.

Iron Carbonyl Complexes of [2.2.2]Hericene as a Rigid Tris(1,3-diene) Ligand.

Hericene is an unusual hexaolefin consisting of three 1,3-diene units located on a rigid bicyclo [2.2.2]octane framework that restricts the geometrical relationships of metal atoms bonded to these olefinic units.

Rapid shift in methane carbon isotopes suggests microbial emissions drove record high atmospheric methane growth in 2020-2022.

The growth rate of the atmospheric abundance of methane (CH) reached a record high of 15.4 ppb yr between 2020 and 2022, but the mechanisms driving the accelerated CH growth have so far been unclear. In this work, we use measurements of the C:C ratio of CH (expressed as C) from NOAA's Global Greenhouse Gas Reference Network and a box model to investigate potential drivers for the rapid CH growth.

Computationally Driven Discovery of a BCR-ABL1 Kinase Inhibitor with Activity in Multidrug-Resistant Chronic Myeloid Leukemia.

The permeability glycoprotein, encoded by the gene, is widely implicated in multidrug resistance (MDR), as it has been shown to reduce the intracellular concentration of most small molecule therapeutics, including the majority of the breakpoint cluster region Abelson proto-oncogene 1 (BCR-ABL1) kinase inhibitors used in the treatment of Philadelphia chromosome positive (Ph+) leukemias. With this in mind, we describe an integrated theoretical and experimental approach to shed light on substituent effects in the pendant anilino moiety of 4-anilinoquinazolines and 4-anilinoquinoline-3-carbonitrile-based kinase inhibitors and their influence on P-gp-mediated efflux. This analysis culminated in the identification of a hydroxylamine-bearing, dual cSRC/BCR-ABL1 kinase inhibitor that exhibits a marked reduction in P-gp-mediated efflux ratio and potent activity in a Ph+ patient-derived cell line (K562) and an MDR-Ph+ patient-derived cell line (K562/Dox) overexpressing P-gp.

Automatic Differentiation for Explicitly Correlated MP2.

Automatic differentiation (AD) offers a route to achieve arbitrary-order derivatives of challenging wave function methods without the use of analytic gradients or response theory. Currently, AD has been predominantly used in methods where first- and/or second-order derivatives are available, but it has not been applied to methods lacking available derivatives. The most robust approximation of explicitly correlated MP2, MP2-F12/3C(FIX)+CABS, is one such method.

Hydrogen bonding in 2,2,2-trifluoroethanol.

Context: 2,2,2-Trifluoroethanol (TFE) is known as a membrane mimetic solvent. The IR spectrum, H NMR spectrum, C NMR spin‒lattice relaxation times (T), and nuclear Overhauser effect (NOE) data are consistent with extensive hydrogen bonding in TFE, but do not lead to structural features of the hydrogen bonding. Hence, DFT computations were carried out.

Trinuclear and Tetranuclear Ruthenium Carbonyl Nitrosyls: Oxidation of a Carbonyl Ligand by an Adjacent Nitrosyl Ligand.

Trinuclear and tetranuclear ruthenium carbonyls of the types Ru(CO)(NO), Ru(N)(CO)(NO), Ru(N)(CO), Ru(N)(CO)(NCO), Ru(CO)(NCO)(NO), Ru(N)(CO)(NO), Ru(N)(CO)(NCO), and Ru(N)(CO) related to species observed experimentally in the chemistry of Ru(CO)(µ-NO) have been investigated using density functional theory. In all cases, the experimentally observed structures have been found to be low-energy structures. The low-energy trinuclear structures typically have a central strongly bent Ru-Ru-Ru chain with terminal CO groups and bridging nitrosyl, isocyanate, and/or nitride ligands across the end of the chain.

Fulminic acid: a quasibent spectacle.

Fulminic acid (HCNO) played a critical role in the early development of organic chemistry, and chemists have sought to discern the structure and characteristics of this molecule and its isomers for over 200 years. The mercurial nature of the extremely flat H-C-N bending potential of fulminic acid, with a nearly vanishing harmonic vibrational frequency at linearity, remains enigmatic and refractory to electronic structure theory, as dramatic variation with both orbital basis set and electron correlation method is witnessed. To solve this problem using rigorous electronic wavefunction methods, we have employed focal point analyses (FPA) to ascertain the limit of optimized linear and bent geometries, corresponding vibrational frequencies, and the HCN + O() → HCNO reaction energy.

Accurate and efficient open-source implementation of domain-based local pair natural orbital (DLPNO) coupled-cluster theory using a t1-transformed Hamiltonian.

We present an efficient, open-source formulation for coupled-cluster theory through perturbative triples with domain-based local pair natural orbitals [DLPNO-CCSD(T)]. Similar to the implementation of the DLPNO-CCSD(T) method found in the ORCA package, the most expensive integral generation and contraction steps associated with the CCSD(T) method are linear-scaling. In this work, we show that the t1-transformed Hamiltonian allows for a less complex algorithm when evaluating the local CCSD(T) energy without compromising efficiency or accuracy.

Comparative Study of Neutral and Cationic SnH: Toward Laboratory Detection of the Cation.

Group 14 MH isomers (M = Si, Ge, Sn, and Pb) have attracted interest due to their radically differing electronic structures from acetylene. To better understand the Sn-H interactions of the neutral and cationic SnH structures, we present the most rigorous study of these systems to date. CCSD(T)/cc-pwCVTZ harmonic frequencies are presented as the first predictions for the neutral and cationic species to date.

Ethynyl Radical Hydrogen Abstraction Energetics and Kinetics Utilizing High-Level Theory.

The ethynyl radical, CH, is found in a variety of different environments ranging from interstellar space and planetary atmospheres to playing an important role in the combustion of various alkynes under fuel-rich conditions. Hydrogen-atom abstraction reactions are common for the ethynyl radical in these contrasting environments. In this study, the CH + HX → CH + X, where HX = HNCO, -HONO, -HONO, CH, and CHOH, reactions have been investigated at rigorously high levels of theory, including CCSD(T)-F12a/cc-pVTZ-F12.

MolSym: A Python package for handling symmetry in molecular quantum chemistry.

A consideration of the point group symmetry of molecules is often advantageous from a computational efficiency standpoint and sometimes necessary for the correct treatment of chemical physics problems. Many modern electronic structure software packages include a treatment of symmetry, but these are sometimes incomplete or unusable outside of that program's environment. Therefore, we have developed the MolSym package for handling molecular symmetry and its associated functionalities to provide a platform for including symmetry in the implementation and development of other methods.

Binuclear Lantern Complexes of All First-Row 3d Metals Scandium to Zinc: Metal-Metal Bond Lengths and Bond Orders, with Measures of Intrinsic Metal-Metal Bond Strength.

The B3LYP and M06-L functionals with the cc-pVTZ basis set are used to study lantern-type binuclear complexes of all the first-row (3d block) metals scandium to zinc in various low-energy spin states, out of which the ground states are predicted. These complexes are studied as models using mostly the unsubstituted formamidinate ligand. For each metal, metal-metal (MM) bond lengths are related to the formal MM bond orders (zero to five), derived by MO analysis and by electron counting.

A Stable Aluminum Tris(dithiolene) Triradical.

A stable aluminum tris(dithiolene) triradical () was experimentally realized through a low-temperature reaction of the sterically demanding lithium dithiolene radical () with aluminum iodide. Compound was characterized by single-crystal X-ray diffraction, UV-vis and EPR spectroscopy, SQUID magnetometry, and theoretical computations. The quartet ground state of triradical has been unambiguously confirmed by variable-temperature continuous wave EPR experiments and SQUID magnetometry.

A wealth of structures for the GeH radical cation: comparison of theory and experiment.

Five structures of GeH and GeH are investigated in this study. Optimized geometries at the CCSD(T)/cc-pwCVQZ-PP level of theory were obtained. Focal point analyses were performed on these optimized geometries to determine relative energies using the CCSD(T) method with polarized basis sets up to quintuple-zeta.

Therapeutic prime/pull vaccination of HSV-2-infected guinea pigs with the ribonucleotide reductase 2 (RR2) protein and CXCL11 chemokine boosts antiviral local tissue-resident and effector memory CD4 and CD8 T cells and protects against recurrent genital herpes.

Following acute herpes simplex virus type 2 (HSV-2) infection, the virus undergoes an asymptomatic latent infection of sensory neurons of dorsal root ganglia (DRG). Chemical and physical stress cause intermittent virus reactivation from latently infected DRG and recurrent virus shedding in the genital mucosal epithelium causing genital herpes in symptomatic patients. While T cells appear to play a role in controlling virus reactivation from DRG and reducing the severity of recurrent genital herpes, the mechanisms for recruiting these T cells into DRG and the vaginal mucosa (VM) remain to be fully elucidated.

Biomimetic Frustrated Lewis Pair Catalysts for Hydrogenation of CO to Methanol at Low Temperatures.

The industrial production of methanol through CO hydrogenation using the Cu/ZnO/AlO catalyst requires harsh conditions, and the development of new catalysts with low operating temperatures is highly desirable. In this study, organic biomimetic FLP catalysts with good tolerance to CO poison are theoretically designed. The base-free catalytic reaction contains the 1,1-addition of CO into a formic acid intermediate and the hydrogenation of the formic acid intermediate into methanol.

A2/A2B to B kidney transplantation outcomes: A single center 7-year experience.

Introduction: Data on long-term outcomes following A2/A2B to B kidney transplants since the 2014 kidney allocation system (KAS) changes are few. The primary aim of this study is to report our 7-year experience with A2/A2B to B kidney transplants and to compare post-transplant outcomes of A2/A2B to a concurrent group of B to B kidney transplants. Additionally, the study evaluates the impact of pre-transplant anti-A1 titers on survival outcomes in A2/A2B transplants.

Convergent ab initio analysis of the multi-channel HOBr + H reaction.

High-level potential energy surfaces for three reactions of hypobromous acid with atomic hydrogen were computed at the CCSDTQ/CBS//CCSDT(Q)/complete basis set level of theory. Focal point analysis was utilized to extrapolate energies and gradients for energetics and optimizations, respectively. The H attack at Br and subsequent Br-O cleavage were found to proceed barrierlessly.

Unusual nucleophilic reactivity of a dithiolene-based N-heterocyclic silane.

While the dithiolene-based N-heterocyclic silane (4) reacts with two equivalents of BX (X = Br, I) to give zwitterionic Lewis adducts 5 and 8, respectively, the parallel reaction of 4 with BCl results in 10, a dithiolene-substituted N-heterocyclic silane, the Si-S bond cleavage. Unlike 5, the labile 8 may be readily converted to 9 BI-mediated cleavage of the Si-N bond. The formation of 5 and 8 confirms that 4 uniquely possesses dual nucleophilic sites: (a) the terminal sulphur atom of the dithiolene moiety; and (b) the backbone carbon of the N-heterocyclic silane unit.

Correction: Pericyclic reaction benchmarks: hierarchical computations targeting CCSDT(Q)/CBS and analysis of DFT performance.

Correction for 'Pericyclic reaction benchmarks: hierarchical computations targeting CCSDT(Q)/CBS and analysis of DFT performance' by Pascal Vermeeren , , 2022, , 18028-18042, https://doi.org/10.1039/D2CP02234F.