Tautomerism of purines. I. N(7)H .dha. N(9)H equilibrium in adenine

Dreyfus, Marc; Dodin, Guy; Bensaude, Olivier; Dubois, Jessica

doi:10.1021/ja00842a011

Cited by 133 publications

(119 citation statements)

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“…Several theoretical and experimental studies have shown that the 9H-amino form is the most stable tautomer of adenine in the gas-phase and in aqueous solution. [55][56][57] However, while the energy difference between 9H-adenine and the minor 7H-tautomer is 7 -8 kcal mol -1 in the gas-phase, the energy gap becomes significantly smaller, when electrostatic interactions with polar solvent molecules are included due to the larger dipole moment of 7H-adenine. 17,58 Consequently, both tautomers co-exist in water.…”

Section: 9(2)° 21 ) While the C(4)-n(9)-c(8) C(2)-n(3)-c(4) Andmentioning

confidence: 99%

Supramolecular Structures and Tautomerism of Carboxylate Salts of Adenine and Pharmaceutically Relevant N⁶-Substituted Adenine

McHugh

Erxleben

2011

Crystal Growth & Design

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Co-crystal and salt formation of the kinetin analogue N 6 -benzyladenine with the pharmaceutically acceptable co-crystal and salt formers maleic acid, oxalic acid, glutaric acid, succinic acid, benzoic acid and fumaric acid has been studied by solid-state and solvent-drop grinding in combination with X-ray powder diffraction. In all cases salt or co-crystal formation was observed. Single crystals of (bzadeH + )(mal -) (1) and (bzadeH + )2(ox 2-) (2) were obtained by solution crystallization and the X-ray structures are reported along with that of (adeH + )2(mal -)2 . ade . 2H2O (3) (bzadeH + = N 6 -benzyladeninium, adeH + = adeninium, ade = adenine, mal -= hydrogen maleate, ox 2-= oxalate). The hydrogen-bonding motifs in 1 -3 are discussed. The salts contain a robust bzadeH + -carboxylate or ade-carboxylate R2 2 (9) heterosynthon involving the protonated Hoogsteen sites (N6-H, N7-H) of bzadeH + and ade. Molecular recognition between the protonated Hoogsteen site and the carboxylate group stabilizes the unusual 7H,9H tautomer of bzadeH + in 2 and the non-canonical 7H-adenine tautomer in 3.* To whom correspondence should be addressed. ABSTRACT Co-crystal and salt formation of the kinetin analogue N 6 -benzyladenine with the pharmaceutically acceptable co-crystal and salt formers maleic acid, oxalic acid, glutaric acid, succinic acid, benzoic acid and fumaric acid has been studied by solid-state and solvent-drop grinding in combination with X-ray powder diffraction. In all cases salt or co-crystal formation was observed. Single crystals of (bzadeH + )(mal -) (1) and (bzadeH + )2(ox 2-) (2) were obtained by solution crystallization and the X-ray structures are reported along with that of (adeH + )2(mal -)2 . ade . 2H2O (3) (bzadeH + = N 6 -benzyladeninium, adeH + = adeninium, ade = adenine, mal -= hydrogen maleate, ox 2-= oxalate). The hydrogen-bonding motifs in 1 -3 are discussed. The salts contain a robust bzadeH + -carboxylate or ade-carboxylate R2 2 (9) heterosynthon involving the protonated Hoogsteen sites (N6-H, N7-H) of bzadeH + and ade. Molecular recognition between the protonated Hoogsteen site and the carboxylate group stabilizes the unusual 7H,9H tautomer of bzadeH + in 2 and the non-canonical 7H-adenine tautomer in 3.3

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Section: 9(2)° 21 ) While the C(4)-n(9)-c(8) C(2)-n(3)-c(4) Andmentioning

confidence: 99%

Supramolecular Structures and Tautomerism of Carboxylate Salts of Adenine and Pharmaceutically Relevant N⁶-Substituted Adenine

McHugh

Erxleben

2011

Crystal Growth & Design

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“…[2]), or by reacting a 1 : 1 mixture without NaOH (eq. [3]): The proton attached to N(9) in solid HAd is involved in a tautomeric equilibrium between N(9) and N(7) in water solutions (19). Hence, CH,Hg+ coordination to N(7) in [CH3HgAd].H20 could not be ruled out.…”

Section: Interactions Of Chjlg+ With Adeninementioning

confidence: 99%

Reactions of the methylmercury(II) ion with adenine and crystal structure of (adeninato-N9)methylmercury (II) monohydrate

Prizant¹,

Olivier²,

Rivest³

et al. 1981

Can. J. Chem.

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Adenine (HAd) reacts with CH3HgX (X = NO3, ClO4) in basic aqueous solution to form a compound [CH3HgAd]•H2O, which crystallizes in the monoclinic space group C2/c, with a = 19.796, b = 7.119, c = 16.471 Å, β = 128.83°, and Z = 8. The CH3Hg+ group is linearly bonded to N(9) of deprotonated adenine and the molecules are held in pairs by two [Formula: see text] hydrogen bonds. With excess adenine, higher complexes of the formula [(CH3Hg)nAd]Xn−1(where n = 2, 3) are formed, in which positions N(9) (deprotonated), N(7), and N(3) are successively filled. Compounds [(CH3Hg)3(Ad-H)]X have been obtained at high pH by substitution of H(9) and an amino hydrogen, and with coordination of a third CH3Hg+ group probably to N(7). Complexation leads to significant changes in the infrared spectra and the 1750–1250 cm−1 regions are correlated with the substitution patterns. The structures are discussed in connection with the basicity of the donors in adenine and the basicity changes of the remaining donors when other atoms are already involved in coordination.

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“…In the 1960s, Manfred Eigen pioneered the T-jump relaxation method using rapid electrical heating in electrolyte solutions to trigger fast chemical reactions, such as the recombination of the enolate ion with H + to form either a keto or enol tautomer (11). Others have since used a similar approach, using a T-jump monitored by UV absorption, to study tautomerism of small molecules on the microsecond time scale (12)(13)(14). These groundbreaking experiments provided the early insights into proton transfer and tautomerization kinetics.…”

mentioning

confidence: 99%

Direct observation of ground-state lactam–lactim tautomerization using temperature-jump transient 2D IR spectroscopy

Peng

Baiz

Tokmakoff

2013

Proc. Natl. Acad. Sci. U.S.A.

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We provide a systematic characterization of the nanosecond groundstate lactam-lactim tautomerization of pyridone derivatives in aqueous solution under ambient conditions using temperature-jump transient 2D IR spectroscopy. Although electronic excited-state tautomerization has been widely studied, experimental work on the ground electronic state, most relevant to chemistry and biology, is lacking. Using 2D IR spectroscopy, lactam and lactim tautomers of 6-chloro-2-pyridone and 2-chloro-4-pyridone are unambiguously identified by their unique cross-peak patterns. Monitoring the correlated exponential relaxation of these signals in response to a laser temperature jump provides a direct measurement of the nanosecond tautomerization kinetics. By studying the temperature, concentration, solvent, and pH dependence, we extract a thermodynamic and kinetic characterization and conclude that the tautomerization proceeds through a two-state concerted mechanism. We find that the intramolecular proton transfer is mediated by bridging water molecules and the reaction barrier is dictated by the release of a proton from pyridone, as would be expected for an efficient Grothusstype proton transfer mechanism.keto-enol tautomerism | multidimensional | time-resolved spectroscopy | ultrafast T automerism of aromatic heterocycles has been extensively studied owing to its importance in biochemical processes such as enzyme catalysis (1), ligand binding (2), and spontaneous mutagenesis (3). To characterize the tautomeric equilibria, researchers have used techniques such as UV absorption (4), circular dichroism (5), X-ray crystallography (3), NMR (6), Raman (7), and IR absorption spectroscopy (8). However, these methods face several challenges to characterizing thermodynamic and kinetic data for tautomeric equilibria and exchange processes. For example, electronic spectra are broad and featureless, which complicates spectral interpretation, particularly for systems with multiple tautomers. Although NMR provides excellent structural resolution, it can only directly monitor chemical exchange in real time on millisecond and longer time scales, rather than the picosecond to nanosecond time scales expected for proton transfer under physiological conditions. From the theoretical point of view, quantum mechanical calculations have been performed extensively to characterize the relative stability of tautomeric systems, their activation barriers, and the reaction mechanisms (9, 10); nevertheless, experimental validation of these predictions is scarce. To provide a characterization under ambient aqueous conditions, we need a technique with both the structural sensitivity to unambiguously identify various tautomers and the time resolution to probe the rapid proton transfer dynamics. To this end, we demonstrate the capability of 2D IR spectroscopy coupled with a nanosecond temperature-jump (Tjump) laser to reveal the nonequilibrium lactam-lactim tautomerization kinetics of pyridone derivatives.Time-resolved studies of tautomerism have a long and storie...

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Tautomerism of purines. I. N(7)H .dha. N(9)H equilibrium in adenine

Cited by 133 publications

References 5 publications

Supramolecular Structures and Tautomerism of Carboxylate Salts of Adenine and Pharmaceutically Relevant N⁶-Substituted Adenine

Supramolecular Structures and Tautomerism of Carboxylate Salts of Adenine and Pharmaceutically Relevant N⁶-Substituted Adenine

Reactions of the methylmercury(II) ion with adenine and crystal structure of (adeninato-N9)methylmercury (II) monohydrate

Direct observation of ground-state lactam–lactim tautomerization using temperature-jump transient 2D IR spectroscopy

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Tautomerism of purines. I. N(7)H .dha. N(9)H equilibrium in adenine

Cited by 133 publications

References 5 publications

Supramolecular Structures and Tautomerism of Carboxylate Salts of Adenine and Pharmaceutically Relevant N6-Substituted Adenine

Supramolecular Structures and Tautomerism of Carboxylate Salts of Adenine and Pharmaceutically Relevant N6-Substituted Adenine

Reactions of the methylmercury(II) ion with adenine and crystal structure of (adeninato-N9)methylmercury (II) monohydrate

Direct observation of ground-state lactam–lactim tautomerization using temperature-jump transient 2D IR spectroscopy

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Supramolecular Structures and Tautomerism of Carboxylate Salts of Adenine and Pharmaceutically Relevant N⁶-Substituted Adenine

Supramolecular Structures and Tautomerism of Carboxylate Salts of Adenine and Pharmaceutically Relevant N⁶-Substituted Adenine