Photoelectron spectroscopic and density functional theoretical studies of the 2′-deoxycytidine homodimer radical anion Photoelectron spectroscopic and density functional theoretical studies of the 2 -deoxycytidine homodimer radical anion

The intact (parent) 2 -deoxycytidine homodimer anion, (dC) 2 •− , was generated in the gas phase (in vacuo) using an infrared desorption/photoemission source and its photoelectron spectrum was recorded using a pulsed, magnetic bottle photoelectron spectrometer. The photoelectron spectrum (PES) revealed a broad peak with the maximum at an electron binding energy between 1.6 and 1.9 eV and with a threshold at ∼1.2 eV. The relative energies and vertical detachment energies of possible anion radicals were calculated at the B3LYP/6-31++G * * level of theory. The most stable anion radicals are the complexes involving combinations of the sugar · · · base and base · · · base interactions. The calculated adiabatic electron affinities and vertical detachment energies of the most stable (dC) 2 •− anions agree with the experimental values. In contrast with previous experimentalcomputational studies on the anionic complexes involving nucleobases with various proton-donors, the electron-induced proton transferred structures of (dC) 2 •− are not responsible for the shape of PES. © 2013 AIP Publishing LLC. [http://d

Excess Electron Attachment to the Nucleoside Pair 2′-Deoxyadenosine (dA)–2′-Deoxythymidine (dT)

The 2′-deoxyadenosine···2′-deoxythymidine (dAdT^•–) radical anion nucleoside pair has been investigated both experimentally and theoretically in the gas phase. The vertical detachment energy (VDE) and adiabatic electron affinity (AEA) were determined by anion photoelectron spectroscopy (PES). The measured photoelectron spectrum features a broad band having an onset at ∼1.1 eV and a maximum at the electron binding energy (EBE) ranging from 1.7 to 1.9 eV. Calculations performed at the M06-2X/6-31++G** level reveal that the observed PES signal is probably due to a dAdT^•– complex in which the thymine of the dT nucleoside forms hydrogen bonds that engage its O7 and O8 atoms as well as the 3′- and 5′-hydroxyl groups of 2′-deoxyadenosine (dA), while dT’s 3′-hydroxyl group interacts with the N1 of dA. In this heterodimer, the excess electron is entirely located on thymine. The biologically relevant Watson–Crick arrangement of the dAdT^•– dimer was found to be substantially less stable (by ∼19 kcal mol^–1 in Gibbs free energy scale) than the above-mentioned configuration; hence, it is not populated in the gas phase

Intermolecular proton transfer induced by excess electron attachment to adenine(formic acid) n (n = 2, 3) hydrogen-bonded complexes

Abstract The propensity of the neutral complexes between both adenine and 9-methyladenine (A/MA) with formic acid (FA) in 1:2 and 1:3 stoichiometries to bind an excess electron was studied using photoelectron spectroscopy and quantum chemistry computational methods. Although an isolated canonical adenine does not support bound valence anions, solvation by one formic acid molecule stabilizes the excess electron on adenine. The adiabatic electron affinities of the A/MA(FA) 2,3 complexes span a range of 0.8-1.23 eV indicating that the anions of 1:2 and 1:3 stoichiometries are substantially more stable than the anionic A-FA dimer (EA = 0.67 eV), which we studied previously and an attachment of electron triggers double-BFPT, confirmed at the MPW1K level of theory, in all the considered systems. Hence, the simultaneous involvement of several molecules capable of forming cyclic hydrogen bonds with adenine remarkably increases its ability to bind an excess electron. The calculated vertical detachment energies for the most stable anions correspond well with those obtained using photoelectron spectroscopy. The possible biological significance of our findings is briefly discussed

Photoelectron Spectroscopy and Computational Modeling of Thymidine Homodimer Anions

The intact thymidine homodimer anion (dT₂^–) was generated in the gas phase using an infrared desorption/photoemission source and recorded by a pulsed photoelectron spectrometer. The photoelectron spectrum (PES) revealed a broad signal with the maximum at electron binding energy ∼2.0 eV and the threshold value at 1.1 eV. The relative energies and vertical detachment energies of the possible anion structures were calculated at the B3LYP/6-31++G­(d,p) level. Here we report that the most stable anion radical homodimer geometries observed in the PES are the anionic nucleoside coordinated by the O8 atom of thymine to the deoxyribose of the second neutral nucleoside. Unlike previous experimental–computational studies on anionic complexes involving nucleobases with proton donors, the electron-induced proton-transferred structures are not responsible for the shape of the PES of dT₂^–

Association of antineutrophil cytoplasmic antibody (ANCA) specificity with the demographic and clinical characteristics of patients with ANCA-associated vasculitides

Introduction Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is characterized by the presence of proteinase-3(PR3) or myeloperoxidase(MPO) ANCA. In over 90% of cases, PR3-ANCA are associated with GPA. However, they are also rarely found in MPA and EGPA. On the other hand, MPO-ANCA being characteristic for MPA (>90% of cases), are also found in about 40% of EGPA and 5% of GPA patients. On the ground of this overlap, clinical importance of ANCA specificity identification has been questioned. Patients and methods We conducted a multicenter study AAV patients (417–GPA, 106–MPA, 102-EGPA; diagnosed between 1990 and 2016), included in the POLVAS registry. Data were systematically collected according to a standardized protocol. Results In the ANCA positive group (anti-MPO, anti-PR3) male to female ratio was 1:1, whereas in ANCA negative subgroup - 1:2, regardless of the AAV diagnosis. Anti-MPO antibodies were present in a significantly older patients. Patients with MPO+ GPA and MPO+ EGPA were older than those with corresponding ANCA-negative GPA and EGPA as well as PR3+ AAV. Moreover, ANCA-negative AAV were characterized by a low risk of ESKD and death. Conclusions The presence and specificity of ANCA in AAV patients is related to sex and age, determines their organ involvement and influences mortality as previously shown. Patients with MPO-ANCA-positive AAV constitute a clinically homogeneous group, whereas PR3-ANCA-positive patients are much more clinically heterogeneous. ANCA negative AAV patients are characterized by better prognosis. Thus, ANCA identification is an indispensable element and should not be omitted in establishing AAV diagnosis