Gas‐Phase Watson–Crick and Hoogsteen Isomers of the Nucleobase Mimic 9‐Methyladenine⋅2‐Pyridone

Abstract

2-Pyridone (pyridin-2-one) is a mimic of the uracil and thymine nucleobases, with only one N--H and C==O group. It provides a single H-bonding site, compared to three for the canonical pyrimidine nucleobases. Employing the supersonically cooled 9-methyladenine2-pyridone (9MAd x 2PY) complex, which is the simplest base pair to mimic adenine-uracil or adenine-thymine, we show that its gas-phase UV spectrum consists of contributions from two isomers. Based on the H-bonding sites of 9-methyladenine, these are the Watson-Crick and Hoogsteen forms. Combining two-color two-photon ionisation (2C-R2PI), UV-UV depletion and laser-induced fluorescence spectroscopies allows separation of the two band systems, revealing characteristic intermolecular in-plane vibrations of the two isomers. The calculated S(0) and S(1) intermolecular frequencies are in good agreement with the experimental ones. Ab initio calculations predict the Watson-Crick isomer to be slightly more stable (D(0)=-16.0 kcal mol(-1)) than the Hoogsteen isomer (D(0)=-15.0 kcal mol(-1)). The calculated free energies Delta(f)G(0) of the Watson-Crick and Hoogsteen isomers agree qualitatively with the experimental isomer concentration ratio of 3:1.

Watson–Crick and Sugar-Edge Base Pairing of Cytosine in the Gas Phase: UV and Infrared Spectra of Cytosine·2-Pyridone

“…This is typical for the CIS calculated intermolecular vibrations of dimers with doubly H-bonded 2PY. [17][18][19][20]35,36 The observed opening ω ′ and stretch σ ′ frequencies show only little variation between the different dimers. The intermolecular vibration frequencies alone do not allow to identify the observed isomers unambiguously.…”

“…15 We have previously employed 2PY to probe the properties of antiparallel double H-bonds formed with 2-aminopyridine, 16 with fluorobenzenes, 17 with uracil, fluorouracil, thymine and other methyluracils, 18,19 and with 9-methyladenine. 20 The dimer of keto-amino Cyt with 2PY can be viewed as a model of the Cyt:uracil mismatch base-pair, which has been observed in crystal structures of RNAs and RNA duplexes. 21,22 The first observation of the Cyt:uracil base pair was in the RNA dodecamer duplex (r-GGACUUCGGUCC) 2 , where the four non-complementary nucleotides in the middle of the sequence do not form a loop but a highly regular double helix.…”

Large-amplitude vibrations of an N–H⋯π hydrogen bonded cis-amide–benzene complex

“…The 2-pyridone (2PY) molecule is a six-ring cis-amide with neighboring N-H and carbonyl groups. 1,2 It serves as a mimic of uracil and/or thymine, [1][2][3][4][5][6][7][8][9][10][11][12][13][14] which exhibit two sets of neighboring N-H and CQO groups. Cis-amides are common in biologically important molecules and significantly influence the structures of nucleic acids, proteins and peptides.…”

Calculation and analysis of vibrational spectra of adenine–thymine, guanine–cytosine, and adenine–uracil complementary pairs in the condensed state

“…The effect of a hydrogen bond on the vibrational spectrum can be determined by comparing the spectra of the isolated molecule and the molecule in the liquid or solid phase, or the spectra of the isolated molecule and the spectra of isolated dimers or an isolated complex of the molecule, for example with water. In all these cases the position of the bands in the IR spectra and their intensity change, which is the major carrier of information about the effect of a hydrogen bond on the change in structure and properties of the molecule.For nucleic acid base pairs, an analogous study has been carried out in the following directions: the change in the IR and Raman spectra of the complementary pairs has been studied in different phase states and different temperature intervals; the spectra of isolated nucleic acid bases have been compared with the spectra of the complementary pairs; the spectra of the pairs adenine-thymine, guanine-cytosine have been compared with the spectra of the corresponding nucleotides and nucleosides [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Usually study of the experimental spectra is accompanied by nonempirical calculations of the normal vibrations and their interpretations.…”