Insights into modifiers effects in differential mobility spectrometry: A data science approach for metabolomics and peptidomics.

Utilizing a data-driven approach, this study investigates modifier effects on compensation voltage in differential mobility spectrometry-mass spectrometry (DMS-MS) for metabolites and peptides. Our analysis uncovers specific factors causing signal suppression in small molecules and pinpoints both signal suppression mechanisms and the analytes involved. In peptides, machine learning models discern a relationship between molecular weight, topological polar surface area, peptide charge, and proton transfer-induced signal suppression. The models exhibit robust performance, offering valuable insights for the application of DMS to metabolites and tryptic peptides analysis by DMS-MS.

Predicting Preferences for Adduct Formation in Electrospray Ionization: The Case Study of Succinic Acid.

A simple theoretical approach is developed that can be used to predict the preference of ion adduct formation (with alkali Li+, Na+, K+ and alkaline earth Ca2+, Mg2+ metals) in electrospray ionization mass spectrometry (ESI-MS) of succinic acid, associated with several protonation/deprotonation equilibria. The applied strategy consists of using a vacuum environment as well as both implicit and explicit solvation of reactive sites and density functional theory as the method of choice. These distinct levels of theory mimic the smooth transition between the condensed environment and free ion in the gas phase. Good correlation between the Gibbs free energies for protonation/adduct formation processes with peak observation in the obtained mass spectra provide insight into the physical basis behind adduct preference and selectivity. This signifies the relationship between microscopic interactions, ionization efficiency, and types of ions that reach the detector.

Untargeted 'SWATH' mass spectrometry-based metabolomics for studying chronic and intermittent exposure to xenobiotics in cohort studies.

Humans are exposed to numerous chemicals daily, for example through nutrition, therapies, and lifestyle choices, which may exert beneficial or toxicological responses. In cohort studies, exposures are frequently assessed using questionnaires, although mass spectrometry-based metabolomics has recently emerged as complementary technique capable of yielding molecular evidence of exposures. Corresponding data processing workflows, however, have been mostly developed for detecting (omnipresent) endogenous metabolites, whereas detection of exogenous chemicals would benefit from fit-for-purpose strategies. In this work, we describe novel strategies for improved exposure detection and their application to data from an untargeted metabolomics study on urine samples from the TransplantLines Food and Nutrition Biobank and Cohort Study (NCT identifier 'NCT02811835'), which includes kidney transplant recipients, potential living kidney donors, and living kidney donors (post-donation). Specifically, we describe a reference spectra generation workflow using exposure-positive samples to detect more and also previously-undetected chronic exposures, and we present a novel approach to establish detection limits based on targeted signal extraction for more reliable and lower-level detection of intermittent exposures. These approaches can contribute to unlocking additional exposure-related information from small-molecule profiling datasets thus increasing data usefulness in metabolomics research and in environmental, food, clinical, and forensic toxicology.

Improvement of d-d interactions in density functional tight binding for transition metal ions with a ligand field model: assessment of a DFTB3+U model on nickel coordination compounds.

To improve the description of interactions among the localized d, f electrons in transition metals, we have introduced a ligand-field motivated contribution into the Density Functional Tight Binding (DFTB) model. Referred to as DFTB3+U, the approach treats the d, f electron repulsions with rotationally invariant orbital-orbital interactions and a Hartree-Fock model; this represents a major conceptual improvement over the original DFTB3 approach, which treats the d, f-shell interactions in a highly averaged fashion without orbital level of description. The DFTB3+U approach is tested using a series of nickel compounds that feature Ni(ii) and Ni(iii) oxidation states. By using parameters developed with the original DFTB3 Hamiltonian and empirical +U parameters (F0/2/4 Slater integrals), we observe that the DFTB3+U model indeed provides substantial improvements over the original DFTB3 model for a number of properties of the nickel compounds, including the population and spin polarization of the d-shell, nature of the frontier orbitals, ligand field splitting and the energy different between low and high spin states at OPBE optimized structures. This proof-of-concept study suggests that with self-consistent parameterization of the electronic and +U parameters, the DFTB3+U model can develop into a promising model that can be used to efficiently study reactive events involving transition metals ion condensed phase systems. The methodology can be integrated with other approximate QM methods as well, such as the extended tight binding (xTB) approach.

Lewis versus Brønsted Acid Activation of a Mn(IV) Catalyst for Alkene Oxidation.

Lewis acid (LA) activation by coordination to metal oxido species has emerged as a new strategy in catalytic oxidations. Despite the many reports of enhancement of performance in oxidation catalysis, direct evidence for LA-catalyst interactions under catalytically relevant conditions is lacking. Here, we show, using the oxidation of alkenes with H2O2 and the catalyst [Mn2(µ-O)3(tmtacn)2](PF6)2 (1), that Lewis acids commonly used to enhance catalytic activity, e.g., Sc(OTf)3, in fact undergo hydrolysis with adventitious water to release a strong Brønsted acid. The formation of Brønsted acids in situ is demonstrated using a combination of resonance Raman, UV/vis absorption spectroscopy, cyclic voltammetry, isotope labeling, and DFT calculations. The involvement of Brønsted acids in LA enhanced systems shown here holds implications for the conclusions reached in regard to the relevance of direct LA-metal oxido interactions under catalytic conditions.

The Irony of Manganocene: An Interplay between the Jahn-Teller Effect and Close-Lying Electronic and Spin States.

Although the unusual structural, magnetic, electronic, and spin characteristics of manganocene has intrigued scientists for decades, a unified explanation and rationalization of its properties has not yet been provided. Results obtained by Multideterminantal Density Functional Theory (MD-DFT), Energy Decomposition Analysis (EDA), and Intrinsic Distortion Path (IDP) methodologies indicate how this uniqueness can be traced back to the manganocene's peculiar electronic structure, mainly, the degenerate ground state and close-lying electronic and spin states.

Selective Photo-Induced Oxidation with O2 of a Non-Heme Iron(III) Complex to a Bis(imine-pyridyl)iron(II) Complex.

Non-heme iron(II) complexes of pentadentate N4Py ( N,N-bis(2-pyridylmethyl)- N-bis(2-pyridyl)methylamine) type ligands undergo visible light-driven oxidation to their iron(III) state in the presence of O2 without ligand degradation. Under mildly basic conditions, however, highly selective base catalyzed ligand degradation with O2, to form a well-defined pyridyl-imine iron(II) complex and an iron(III) picolinate complex, is accelerated photochemically. Specifically, a pyridyl-CH2 moiety is lost from the ligand, yielding a potentially N4 coordinating ligand containing an imine motif. The involvement of reactive oxygen species other than O2 is excluded; instead, deprotonation at the benzylic positions to generate an amine radical is proposed as the rate determining step. The selective nature of the transformation holds implications for efforts to increase catalyst robustness through ligand design.

A Non-Heme Iron Photocatalyst for Light-Driven Aerobic Oxidation of Methanol.

Non-heme (L)FeIII and (L)FeIII -O-FeIII (L) complexes (L=1,1-di(pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)ethan-1-amine) underwent reduction under irradiation to the FeII state with concomitant oxidation of methanol to methanal, without the need for a secondary photosensitizer. Spectroscopic and DFT studies support a mechanism in which irradiation results in charge-transfer excitation of a FeIII -µ-O-FeIII complex to generate [(L)FeIV =O]2+ (observed transiently during irradiation in acetonitrile), and an equivalent of (L)FeII . Under aerobic conditions, irradiation accelerates reoxidation from the FeII to the FeIII state with O2 , thus closing the cycle of methanol oxidation to methanal.

Benchmarking density functional tight binding models for barrier heights and reaction energetics of organic molecules.

Density Functional Tight Binding (DFTB) models are two to three orders of magnitude faster than ab initio and Density Functional Theory (DFT) methods and therefore are particularly attractive in applications to large molecules and condensed phase systems. To establish the applicability of DFTB models to general chemical reactions, we conduct benchmark calculations for barrier heights and reaction energetics of organic molecules using existing databases and several new ones compiled in this study. Structures for the transition states and stable species have been fully optimized at the DFTB level, making it possible to characterize the reliability of DFTB models in a more thorough fashion compared to conducting single point energy calculations as done in previous benchmark studies. The encouraging results for the diverse sets of reactions studied here suggest that DFTB models, especially the most recent third-order version (DFTB3/3OB augmented with dispersion correction), in most cases provide satisfactory description of organic chemical reactions with accuracy almost comparable to popular DFT methods with large basis sets, although larger errors are also seen for certain cases. Therefore, DFTB models can be effective for mechanistic analysis (e.g., transition state search) of large (bio)molecules, especially when coupled with single point energy calculations at higher levels of theory. © 2017 Wiley Periodicals, Inc.

Unique mononuclear Mn(II) complexes of an end-off compartmental Schiff base ligand: experimental and theoretical studies on their bio-relevant catalytic promiscuity.

Three new mononuclear manganese(ii) complexes, namely [Mn(HL)2]·2ClO4 (1), [Mn(HL)(N(CN)2)(H2O)2]·ClO4 (2) and [Mn(HL)(SCN)2] (3) [LH = 4-tert-butyl-2,6-bis-[(2-pyridin-2-yl-ethylimino)-methyl]-phenol], have been synthesized and structurally characterized. An "end-off" compartmental ligand (LH) possesses two symmetrical compartments with N2O binding sites but accommodates only one manganese atom instead of two due to the protonation of the imine nitrogen of one compartment. Although all three complexes are mononuclear, complex 1 is unique as it has a 1 : 2 metal to ligand stoichiometry. The catalytic promiscuity of complexes 1-3 in terms of two different bio-relevant catalytic activities namely catecholase and phenoxazinone synthase has been thoroughly investigated. EPR and cyclic voltametric studies reveal that radical formation rather than metal centered redox participation is responsible for their catecholase-like and phenoxazinone synthase-like catalytic activity. A computational approach suggests that imine bond bound radical generation rather than phenoxo radical formation is most likely responsible for the oxidizing properties of the complexes.

Magnetic anisotropy in "scorpionate" first-row transition-metal complexes: a theoretical investigation.

In this work we have analyzed in detail the magnetic anisotropy in a series of hydrotris(pyrazolyl)borate (Tp(-)) metal complexes, namely [VTpCl](+), [CrTpCl](+), [MnTpCl](+), [FeTpCl], [CoTpCl], and [NiTpCl], and their substituted methyl and tert-butyl analogues with the goal of observing the effect of the ligand field on the magnetic properties. In the [VTpCl](+), [CrTpCl](+), [CoTpCl], and [NiTpCl] complexes, the magnetic anisotropy arises as a consequence of out-of-state spin-orbit coupling, and covalent changes induced by the substitution of hydrogen atoms on the pyrazolyl rings does not lead to drastic changes in the magnetic anisotropy. On the other hand, much larger magnetic anisotropies were predicted in complexes displaying a degenerate ground state, namely [MnTpCl](+) and [FeTpCl], due to in-state spin-orbit coupling. The anisotropy in these systems was shown to be very sensitive to perturbations, for example, chemical substitution and distortions due to the Jahn-Teller effect. We found that by substituting the hydrogen atoms in [MnTpCl](+) and [FeTpCl] by methyl and tert-butyl groups, certain covalent contributions to the magnetic anisotropy energy (MAE) could be controlled, thereby achieving higher values. Moreover, we showed that the selection of ion has important consequences for the symmetry of the ground spin-orbit term, opening the possibility of achieving zero magnetic tunneling even in non-Kramers ions. We have also shown that substitution may also contribute to a quenching of the Jahn-Teller effect, which could significantly reduce the magnetic anisotropy of the complexes studied.

Role of spin state and ligand charge in coordination patterns in complexes of 2,6-diacetylpyridinebis(semioxamazide) with 3d-block metal ions: a density functional theory study.

We report here a systematic computational study on the effect of the spin state and ligand charge on coordination preferences for a number of 3d-block metal complexes with the 2,6-diacetylpyridinebis(semioxamazide) ligand and its mono- and dianionic analogues. Our calculations show excellent agreement for the geometries compared with the available X-ray structures and clarify some intriguing experimental observations. The absence of a nickel complex in seven-coordination is confirmed here, which is easily explained by inspection of the molecular orbitals that involve the central metal ion. Moreover, we find here that changes in the spin state lead to completely different coordination modes, in contrast to the usual situation that different spin states mainly result in changes in the metal-ligand bond lengths. Both effects result from different occupations of a combination of π- and σ-antibonding and nonbonding orbitals.