Superior performance of the machine-learning GAP force field for fullerene structures

Structural Chemistry - Carbon force fields are widely used for obtaining structural properties of carbon nanomaterials. We evaluate the performance of a wide range of carbon force fields for...     

Computational design of bio-inspired carnosine-based HOBr antioxidants

During a respiratory burst the enzyme myeloperoxidase generates significant amounts of hypohalous acids (HOX, X?=?Cl and Br) in order to inflict oxidative damage upon invading pathogens. However, excessive production of these potent oxidants is associated with numerous inflammatory diseases. It has been suggested that the endogenous antioxidant carnosine is an effective HOCl scavenger. Recent computational and experimental studies suggested that an intramolecular Cl⁺ transfer from the imidazole ring to the terminal amine might play an important role in the antioxidant activity of carnosine. Based on high-level ab initio calculations, we propose a similar reaction mechanism for the intramolecular Br⁺ transfer in carnosine. These results suggest that carnosine may be an effective HOBr scavenger. On the basis of the proposed reaction mechanism, we proceed to design systems that share similar structural features to carnosine but with enhanced HOX scavenging capabilities for X?=?Cl and Br. We find that (i) elongating the β-alanyl-glycyl side chain by one carbon reduces the reaction barriers by up to 44%, and (ii) substituting the imidazole ring with strong electron-donating groups reduces the reaction barriers by similar amounts. We also show that the above structural and electronic effects are largely additive. In an antioxidant candidate that involves both of these effects the reaction barriers are reduced by 71%.     

Real-time 2D NMR identification of analytes undergoing continuous chromatographic separation

We have recently proposed and demonstrated an approach that enables the acquisition of multidimensional nuclear magnetic resonance (NMR) spectra within a single scan. A promising application opened up by this new accelerated form of data acquisition concerns the possibility of monitoring in real time the chemical nature of analytes subject to a continuous flow. The present paper illustrates such potential, with the real-time acquisition of a series of 2D 1H NMR spectra arising from a mixture of compounds subject to a continuous liquid chromatography (LC) separation. This real-time 2D NMR identification of chemicals eluted minutes apart under usual LC-NMR conditions differs from the way in which LC-2D NMR has hitherto been carried out, which relies on stopped-flow modes of operations whereby fractions are first collected and then subject to individual, aliquot-by-aliquot analyses. The real-time LC-2D NMR experiment hereby introduced can be implemented in a straightforward manner using modern commercial LC-NMR hardware, thus opening up immediate possibilities in high-throughput characterizations of complex molecules.     

Effect of substituents on the strength of N-X (X = H, F, and Cl) bond dissociation energies: a high-level quantum chemical study

The effect of substituents on the strength of N-X (X = H, F, and Cl) bonds has been investigated using the high-level W2w thermochemical protocol. The substituents have been selected to be representative of the key functional groups that are likely to be of biological, synthetic, or industrial importance for these systems. We interpreted the effects through the calculation of relative N-X bond dissociation energies (BDE) or radical stabilization energies (RSE(NX)). The BDE and RSE(NX) values depend on stabilizing/destabilizing effects in both the reactant molecule and the product radical of the dissociation reactions. To assist us in the analysis of the substituent effects, a number of additional thermochemical quantities have been introduced, including molecule stabilization energies (MSE(NX)). We find that the RSE(NH) values are (a) increased by electron-donating alkyl substituents or the vinyl substituent, (b) increased in imines, and (c) decreased by electron-withdrawing substituents such as CF(3) and carbonyl moieties or through protonation. A different picture emerges when considering the RSE(NF) and RSE(NCl) values because of the electronegativities of the halogen atoms. The RSE(NX)s differ from the RSE(NH) values by an amount related to the stabilization of the N-halogenated molecules and given by MSE(NX). We find that substituents that stabilize/destabilize the radicals also tend to stabilize/destabilize the N-halogenated molecules. As a result, N-F- and N-Cl-containing molecules that include alkyl substituents or correspond to imines are generally associated with RSE(NF) and RSE(NCl) values that are less positive or more negative than the corresponding RSE(NH). In contrast, N-F- and N-Cl-containing molecules that include electron-withdrawing substituents or are protonated are generally associated with RSE(NF) and RSE(NCl) values that are more positive or less negative than the corresponding RSE(NH).     

Selective site controlled nucleophilic attacks in 5-membered ring phosphate esters: unusual C-O vs. common P-O bond cleavage

Clean endocyclic C-O bond cleavage has been achieved in the reactions of 5-membered phosphate triesters with various nucleophiles.     

A computational foray into the mechanism and catalysis of the adduct formation reaction of guanine with crotonaldehyde

Crotonaldehyde, a common environmental pollutant and product of endogenous lipid peroxidation, reacts with guanine to form DNA adducts with pronounced genotoxicity and mutagenicity. Here, we explore the molecular mechanism of this adduct formation using double-hybrid density functional theory methods. The reaction can be envisaged to occur in a two-step fashion via an aza-Michael addition leading to an intermediate ring-open adduct followed by a cyclization reaction giving the mutagenic ring-closed adduct. We find that (i) a 1,2-type addition is favored over a 1,4-type addition for the aza-Michael addition, and (ii) an initial tautomerization of the guanine moiety in the resulting ring-open adduct significantly reduces the barrier toward cyclization compared to the direct cyclization of the ring-open adduct in its keto-form. Overall, the aza-Michael addition is found to be rate-determining. We further find that participation of a catalytic water molecule significantly reduces the energy barriers of both the addition and cyclization reaction. © 2018 Wiley Periodicals, Inc.     

Spectroscopy of Ethylenedione and Ethynediolide: A Reinvestigation

In an effort to characterize the electronic states of ethylenedione, OCCO, photoelectron‐photofragment coincidence (PPC) spectroscopy was applied to measure anions at m/z 56 and 57 using a pulsed discharge of glyoxal vapor and N₂O. PPC measurements at a photon energy of 3.20 eV yield photoelectron spectra in coincidence with either neutral photofragments or stable neutral products. The measurements showed that primarily stable neutral products were formed, with photoelectron spectra consistent with the oxyallyl diradical, C₃H₄O, and acetone enolate radical, C₃H₅O. The spectra were also found to have features nearly identical to those reported for OCCO and HOCCO by Sanov and co‐workers. The stability of the neutral products, as well as an examination of spectra reported for the oxyallyl anion and acetone enolate show that the previous assignments of OCCO and HOCCO are in error, and are instead attributed here to the oxyallyl diradical, C₃H₄O, and the acetone enolate radical, C₃H₅O.     

Self-immolative polymers

Smart polymers are special kinds of polymeric molecules that respond to external stimuli. We have developed a novel smart polymer designed to sequentially disassemble into its building blocks upon initiation by a triggering event at the polymer head. The polymer structure is based on a polyurethane backbone that disassembles through a domino-like, 1,6-elimination and decarboxylation reactions. We synthesized a self-immolative polymer that amplifies a single cleavage reaction into multiple release of fluorogenic molecules and confirmed the head-to-tail disassembly concept. These polymers can be used to prepare highly sensitive molecular sensors with large signal-to-noise ratios. The sensors should be useful for the detection of a wide range of biological and chemical activities through use of the appropriate trigger at the polymer head.     

Label-free LC-MS/MS quantitative proteomics for large-scale biomarker discovery in complex samples

Proteomic platforms that enable researchers to profile a high number of proteins across large sets of complex samples hold a great potential for biomarker discovery. LC-MS/MS-based methods can be used to analyse many samples without the need for protein labelling. As the analysis is a sequential process, the performance of the system has to be consistent throughout the entire experiment. In this study we used a set of spiked serum samples as well as a set of 55 clinical serum samples from schizophrenia patients and healthy volunteers to show that the label-free proteomic approach yields reproducible results across a large number of samples and can be used to accurately measure the relative protein abundance. Using this approach, we identified 1709 serum proteins covering a dynamic range of over three orders of magnitude. We believe that label-free quantitative proteomics is especially suited for biomarker discovery in large sample sets.