Enol Tautomers of Watson−Crick Base Pair Models Are Metastable Because of Nuclear Quantum Effects

Pérez, Antonio Solanas; Tuckerman, Mark E.; Hjalmarson, Harold P.; Lilienfeld, O. Anatole von

doi:10.1021/ja102004b

Cited by 91 publications

(100 citation statements)

References 79 publications

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“…Several tautomerization mechanisms have been proposed. For example, intermolecular double-proton tunneling has been suggested for the spontaneous formation of enol tautomers in Watson-Crick base pairs (38) and has been observed for imidazole and pyrazole in nonaqueous solvents at −100°C (39). We precluded the possibility of dimer formation in water because both the FTIR spectra (23) and T-jump relaxation rates (Fig.…”

Section: Resultsmentioning

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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Section: Resultsmentioning

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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“…10,12,[41][42][43] The intramolecular PT mechanism has received a particular attention since nuclear quantum effects could inhibit the formation of certain tautomeric forms, which would avoid DNA 13 damage. 44 Yet, experimental evidences have indicated that tautomerism can provide a molecular explanation for the mutagenic properties. 34 Moreover, the intermolecular tautomeric equilibrium in electronic excited states 45 can favor specific tautomeric forms.…”

Section: Figurementioning

confidence: 99%

Energy Barrier Reduction for the Double Proton-Transfer Reaction in Guanine–Cytosine DNA Base Pair on a Gold Surface

et al. 2015

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ABSTRACT. We investigate, by means of first-principles calculations, the impact of a gold surface on the proton-transfer of the guanine-cytosine (GC) DNA base pair. Our calculations employ density functional improvements to correct van der Waals interactions and properly treat a weakly bound GC pair at an Au(111) surface. We adopted the simultaneous double proton-transfer (SDPT) mechanism proposed by Löwdin, which may lead to a spontaneous mutation in the structure of DNA from specific tautomerization involving the base pairs. Our calculated differences in the energetics and kinetics of the SDPT in the GC pair, when in contact with an inert gold surface, indicate a reduction of about 31% in the activation energy barrier of the GC/Au(111) tautomeric equilibrium. This finding gives strong evidence that tautomerism of DNA base pairs, binding to a noble surface, may be indeed relevant for the assessment of a possible point mutation, which could be induced by the presence of gold nanoparticles during DNA replication.

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“…The combination of 4 bases and 20 amino acids are the correct solutions to a genetic information optimization problem with enzymes central to the quantum coherence (picture a particle in quantum mechanics where all of the alternative possibilities open to the system co-exist as a superposition in a pure state). Quantum directed mutations can theoretically occur via proton tunneling where protons can plow through the normal thermodynamic energy barrier and cause nucleotide bases to vacillate between two tautomeric states thus causing non-canonical base pairing and consequently mutations (Perez et al, 2010). DNA, acting as a quantum computer, can simultaneously examine and select a beneficial state (mutation) while held in superposition and then decohere, collapsing back into the classical world (McFadden et al 1999).…”

Section: Quantum Mechanics and The Matter Of Lifementioning

confidence: 99%

Quantum Microbiology

2011

Current Issues in Molecular Biology

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During his famous 1943 lecture series at Trinity College Dublin, the reknown physicist Erwin Schrödinger discussed the failure and challenges of interpreting life by classical physics alone and that a new approach, rooted in Quantum principles, must be involved. Quantum events are simply a level of organization below the molecular level. This includes the atomic and subatomic makeup of matter in microbial metabolism and structures, as well as the organic, genetic information codes of DNA and RNA. Quantum events at this time do not elucidate, for example, how specific genetic instructions were first encoded in an organic genetic code in microbial cells capable of growth and division, and its subsequent evolution over 3.6 to 4 billion years. However, due to recent technological advances, biologists and physicists are starting to demonstrate linkages between various quantum principles like quantum tunneling, entanglement and coherence in biological processes illustrating that nature has exerted some level quantum control to optimize various processes in living organisms. In this article we explore the role of quantum events in microbial processes and endeavor to show that after nearly 67 years, Schrödinger was prophetic and visionary in his view of quantum theory and its connection with some of the fundamental mechanisms of life.

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Enol Tautomers of Watson−Crick Base Pair Models Are Metastable Because of Nuclear Quantum Effects

Cited by 91 publications

References 79 publications

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

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

Energy Barrier Reduction for the Double Proton-Transfer Reaction in Guanine–Cytosine DNA Base Pair on a Gold Surface

Quantum Microbiology

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