OH Radical‐Induced Oxidation in Nucleosides and Nucleotides Unraveled by Tandem Mass Spectrometry and Infrared Multiple Photon Dissociation Spectroscopy

Posted on 6 October 2023 by

Oxidative lesions in DNA model systems, induced by OH⋅, have been structurally characterized by infrared multiple photon dissociation spectroscopy and density functional theory calculations. The addition of one oxygen atom occurs on the nucleobase moiety.

Abstract

OH⋅-induced oxidation products of DNA nucleosides and nucleotides have been structurally characterized by collision-induced dissociation tandem mass spectrometry (CID-MS²) and Infrared Multiple Photon Dissociation (IRMPD) spectroscopy. CID-MS² results have shown that the addition of one oxygen atom occurs on the nucleobase moiety. The gas-phase geometries of +16 mass increment products of 2’-deoxyadenosine (dA(O)H⁺), 2’-deoxyadenosine 5’-monophosphate (dAMP(O)H⁺), 2’-deoxycytidine (dC(O)H⁺), and 2’-deoxycytidine 5’-monophosphate (dCMP(O)H⁺) are extensively investigated by IRMPD spectroscopy and quantum-chemical calculations. We show that a carbonyl group is formed at the C8 position after oxidation of 2’-deoxyadenosine and its monophosphate derivative. For 2’-deoxycytidine and its monophosphate derivative, the oxygen atom is added to the C5 position to form a C−OH group. IRMPD spectroscopy has been employed for the first time to provide direct structural information on oxidative lesions in DNA model systems.

Controlling the Crystallisation and Hydration State of Crystalline Porous Organic Salts

Posted on 6 October 2023 by

High throughput screening was used to rapidly identify a new crystalline porous salt (CPOS). Using flow chemistry, the CPOS was scaled, and the material was shown to have permeant porosity with a carbon dioxide uptake of 4.3 mmol/g at 195 K, making it one of the most porous and scalable CPOS reported to date.

Abstract

Crystalline porous organic salts (CPOS) are a subclass of molecular crystals. The low solubility of CPOS and their building blocks limits the choice of crystallisation solvents to water or polar alcohols, hindering the isolation, scale-up, and scope of the porous material. In this work, high throughput screening was used to expand the solvent scope, resulting in the identification of a new porous salt, CPOS-7, formed from tetrakis(4-sulfophenyl)methane (TSPM) and tetrakis(4-aminophenyl)methane (TAPM). CPOS-7 does not form with standard solvents for CPOS, rather a hydrated phase (Hydrate2920) previously reported is isolated. Initial attempts to translate the crystallisation to batch led to challenges with loss of crystallinity and Hydrate2920 forming favorably in the presence of excess water. Using acetic acid as a dehydrating agent hindered formation of Hydrate2920 and furthermore allowed for direct conversion to CPOS-7. To allow for direct formation of CPOS-7 in high crystallinity flow chemistry was used for the first time to circumvent the issues found in batch. CPOS-7 and Hydrate2920 were shown to have promise for water and CO₂ capture, with CPOS-7 having a CO₂ uptake of 4.3 mmol/g at 195 K, making it one of the most porous CPOS reported to date.

Closed Synthetic Cycle for Nickel‐Based Dihydrogen Formation

Posted on 6 October 2023 by

Nickel complexes with a N-heterocyclic carbene ligand (TIMEN^iPr) have been synthesized and characterized. Starting from the Ni⁰ precursor, a Ni^II hydride is synthesized that reacts with protons to form a rare Ni−H₂ intermediate, which was studied by NMR spectroscopy and DFT calculations. Further reduction closes the synthetic cycle.

Abstract

Dihydrogen evolution was observed in a two-step protonation reaction starting from a Ni⁰ precursor with a tripodal N-heterocyclic carbene (NHC) ligand. Upon the first protonation, a Ni^II monohydride complex was formed, which was isolated and fully characterized. Subsequent protonation yields H₂ via a transient intermediate (INT) and an isolable Ni^II acetonitrile complex. The latter can be reduced to regenerate its Ni⁰ precursor. The mechanism of H₂ formation was investigated by using a deuterated acid and scrutinized by ¹H NMR spectroscopy and gas chromatography. Remarkably, the second protonation forms a rare nickel dihydrogen complex, which was detected and identified in solution and characterized by ¹H NMR spectroscopy. DFT-based computational analyses were employed to propose a reaction profile and a molecular structure of the Ni−H₂ complex. Thus, a dihydrogen-evolving, closed-synthetic cycle is reported with a rare Ni−H₂ species as a key intermediate.

Computational Energy Spectra of the H2O@C70 Endofullerene

Posted on 6 October 2023 by

Quantum-mechanical investigations in endofullerenes: the effect of uniaxial distortion on quantized states of the nanoconfined water molecule

Abstract

A water molecule confined inside the C₇₀ fullerene was quantum-mechanically described using a computational approach within the MCTDH framework. Such procedure involves the development of a full-dimensional coupled hamiltonian, with an exact kinetic energy operator, including all rotational, translational and vibrational degrees of freedom of the endofullerene system. In turn, through an effective pairwise potential model, the ground and rotationally excited states of the encapsulated H₂O inside the C₇₀ cage were calculated, and traced back to the isotropic case of the H₂O@C₆₀ endofullerene in order to understand the nature and physical origin of the symmetry breaking observed experimentally in the latter system. Moreover, the computational scheme used here allows to study the quantization of the translational movement of the encapsulated water molecule inside the C₇₀ fullerene, and to investigate the confinement effects in the vibrational energy levels of the H₂O@C₇₀ system.

Effects of Intra‐Base Pair Proton Transfer on Dissociation and Singlet Oxygenation of 9‐Methyl‐8‐Oxoguanine−1‐Methyl‐Cytosine Base‐Pair Radical Cations

Posted on 6 October 2023 by nMay Myat Moe, nMidas Tsai, nJianbo Liun

Intra-base pair proton transfer enhances the oxidizability of the 8-oxoguanine radical within a Watson–Crick 8-oxoguanine–cytosine base-pair radical cation, and the proton transfer also leads to non-statistical base-pair dissociation upon collisional activation.

Abstract

8-Oxoguanosine is the most common oxidatively generated base damage and pairs with complementary cytidine within duplex DNA. The 8-oxoguanosine−cytidine lesion, if not recognized and removed, not only leads to G-to-T transversion mutations but renders the base pair being more vulnerable to the ionizing radiation and singlet oxygen (¹O₂) damage. Herein, reaction dynamics of a prototype Watson−Crick base pair [9MOG ⋅ 1MC]⋅⁺, consisting of 9-methyl-8-oxoguanine radical cation (9MOG⋅⁺) and 1-methylcystosine (1MC), was examined using mass spectrometry coupled with electrospray ionization. We first detected base-pair dissociation in collisions with the Xe gas, which provided insight into intra-base pair proton transfer of 9MOG⋅⁺ ⋅ 1MC [9MOG − H_N1]⋅ ⋅ [1MC+H_N3′]⁺ and subsequent non-statistical base-pair separation. We then measured the reaction of [9MOG ⋅ 1MC]⋅⁺ with ¹O₂, revealing the two most probable pathways, C5-O₂ addition and H_N7-abstraction at 9MOG. Reactions were entangled with the two forms of 9MOG radicals and base-pair structures as well as multi-configurations between open-shell radicals and ¹O₂ (that has a mixed singlet/triplet character). These were disentangled by utilizing approximately spin-projected density functional theory, coupled-cluster theory and multi-referential electronic structure modeling. The work delineated base-pair structural context effects and determined relative reactivity toward ¹O₂ as [9MOG − H]⋅>9MOG⋅⁺>[9MOG − H_N1]⋅ ⋅ [1MC+H_N3′]⁺≥9MOG⋅⁺ ⋅ 1MC.

Pair Distribution Function from Liquid Jet Nanoparticle Suspension using Femtosecond X‐ray Pulses

Posted on 6 October 2023 by

Femtosecond pair distribution function data measured on a suspension of nanoparticles using a liquid jet are discussed and compared with synchrotron data.

Abstract

X-ray scattering data measured on femtosecond timescales at the SACLA X-ray Free Electron Laser (XFEL) facility on a suspension of HfO₂ nanoparticles in a liquid jet were used for pair distribution function (PDF) analysis. Despite a non-optimal experimental setup resulting in a modest Q_max of ~8 Å⁻¹, a promising PDF was obtained. The main features were reproduced when comparing the XFEL PDF to a PDF obtained from data measured at the PETRA III synchrotron light source. Refining structural parameters such as unit cell dimension and particle size from the XFEL PDF provided reliable values. Although the reachable Q_max limited the obtainable information, the present results indicate that good quality PDFs can be obtained on femtosecond timescales if the experimental conditions are further optimized. The study therefore encourages a new direction in ultrafast structural science where structural features of amorphous and disordered systems can be studied.

Chemical Composition of Essential Oil from Mosses from the Brazilian Atlantic Forest

Posted on 6 October 2023 by

Abstract

This study aimed to report the unprecedented volatile composition of the mosses Phyllogonium viride BRID, Orthotichella rigida (MÜLL.HAL.) B. H. ALLEN & MAGILL and Schlotheimia rugifolia (HOOK.) SCHWÄGR occurring in the Brazilian Atlantic Forest, in order to elucidate the chemical composition of these species and enrich the chemotaxonomic knowledge of mosses. 28 compounds were identified, the major constituent being hexadecanoic acid, also known as palmitic acid, specifically P. viride com (38.55 %), O. rigida com (17.17 %) and S. rugifolia com (24.94 %), followed by phytol, P. viride com (3.92 %), O. rigida com (28.57 %) and S. rugifolia com (36.13 %). In addition, there was a prevalence of aliphatic hydrocarbons (25 %) and fatty acids (17.8 %) in the evaluated samples. These data contribute to the generation of new scientific information about the chemical constitution of mosses, still little studied, enriching the chemotaxonomic collection of the taxon.

Terpenoids from Euphorbia helioscopia and Their Cytotoxic Activities against H1975 Cells

Posted on 6 October 2023 by

Abstract

Three previously undescribed diterpenoids, helioscopnoids A–C, and eight known compounds were isolated from the whole plants of Euphorbia helioscopia. Their structures were established by extensive analysis of spectra and data comparison with previous literatures. Among them, compound 4 was identified as 24,24-dimethoxy-25,26,27-trinoreuphan-3β-ol with revised configurations of C-13, C-14, and C-17 (13R*, 14R*, 17R*). Cytotoxicity assays revealed that all compounds exhibited varying levels of cytotoxicity against H1975 cells, with compound 9 displaying the most potent activity, as indicated by cell viability rates of 18.13 % and 20.76 % at concentrations of 20 μM and 5 μM, respectively. This study expands the understanding of E. helioscopia terpenoids’ structural diversity and biological activities, contributing to the exploration of potential therapeutic applications.

Bioorthogonal Chemistry in Translational Research: Advances and Opportunities

Posted on 6 October 2023 by nRitapa Chaudhuri, nSemantee Bhattacharya, nJyotirmayee Dashn

The bioorthogonal toolbox comprises reaction handles for click reactions (CuAAC), strain-promoted reactions (IEDDA cycloaddition), and enzymatic reactions (Staudinger ligation). These reactions have revolutionized the field of chemical biology by providing researchers with powerful tools to investigate and manipulate biomolecules within living systems with precision and control.

Abstract

Bioorthogonal chemistry is a rapidly expanding field of research that involves the use of small molecules that can react selectively with biomolecules in living cells and organisms, without causing any harm or interference with native biochemical processes. It has made significant contributions to the field of biology and medicine by enabling selective labeling, imaging, drug targeting, and manipulation of bio-macromolecules in living systems. This approach offers numerous advantages over traditional chemistry-based methods, including high specificity, compatibility with biological systems, and minimal interference with biological processes. In this review, we provide an overview of the recent advancements in bioorthogonal chemistry and their current and potential applications in translational research. We present an update on this innovative chemical approach that has been utilized in cells and living systems during the last five years for biomedical applications. We also highlight the nucleic acid-templated synthesis of small molecules by using bioorthogonal chemistry. Overall, bioorthogonal chemistry provides a powerful toolset for studying and manipulating complex biological systems, and holds great potential for advancing translational research.

Metameric Brooker’s versus Reichardt’s zwitterions: Conformational metamorphosis on optoelectronic properties, using coupled‐perturbed and finite field theories

Posted on 6 October 2023 by nDivya Pant, nSanyasi Sithan

Intrinsic conformational preferences (twisted Reichardt's vs. planar Brooker's zwitterions) through metameric induction (chemical perturbation) found to have strong impact on various tensorial and non-tensorial properties. Orbital energies, and because of this, absorption, and charge transfer properties of the metamers were found to be strongly affected. Reichardt's mode was found to be more efficient NLO-phore (large hyperpolarizability) than Brooker's mode. Brooker's mode was found to be effective in addressing the transparency trade-off problem than Reichardt's mode.

Abstract

This contribution reports influences of unusual conformational metamorphosis shown by Reichardt's and Brooker's metameric zwitterions by an earlier work, on various intrinsic electronic and optoelectronic properties. Detailed quantum mechanical investigations were carried out using HF, B3LYP, CAM-B3LYP, and ωB97xD methodologies. Observations suggest that whereas certain properties were directly and strongly influenced by the conformation preferences (twisted vs. planar), others were not strongly inclined to such conformational transformations. Interestingly, even with inherent conformational differences, observed properties were found to have only one major contributing component in each molecule and can be beneficial in one dimensional (1D) or pseudo-1D chromophore design strategies. Both coupled perturbed (CP) and finite field (FF) theories were used to compute dipole moments, polarizabilities, and hyperpolarizabilities, and so on, and excellent agreements (or exact matching results) were observed between the two theories. Reichardt's metamer was found to be more efficient in many aspects than Brooker's metamer. The direct and strong influences of metameric manipulations on structure–property correlations shown in this work can be adopted as a useful strategy for efficient chromophore design. Such a strategy is useful in the field of nonlinear optics, and may also find applications in various other areas of material sciences.