Looking for the Elusive Imine Tautomer of Creatinine: Different States of Aggregation Studied by Quantum Chemistry and Molecular Spectroscopy

Abstract

New spectroscopic experiments and state-of-the-art quantumchemical computations of creatinine in different aggregation states unequivocally unveiled a significant tuning of tautomeric equilibrium by the environment: from the exclusive presence of the amine tautomer in the solid state and aqueous solution to a mixture of amine and imine tautomers in the gas phase. Quantum-chemical calculations predict the amine species as the most stable tautomer by about 30 kJ mol À 1 in condensed phases. On the contrary, moving to the isolated forms, both Z and E imine isomers become more stable by about 7 kJ mol À 1 .Since the imine isomers and one amine tautomer are separated by significant energy barriers, all of them should be present in the gas phase. This prediction has indeed been confirmed by high-resolution rotational spectroscopy, which provides the first experimental characterization of the elusive imine tautomer. The interpretation of the complicated hyperfine structure of the rotational spectrum, originated by three 14 N nuclei, makes it possible to use the spectral signatures as a sort of fingerprint for each individual tautomer in the complex sample.

Development, Validation, and Pilot Application of a Generalized Fluctuating Charge Model for Computational Spectroscopy in Solution

“…This result suggests a higher stability of the amine tautomer in aqueous solution, in agreement with previous results. 35 These conclusions are corroborated by the comparison of (i) the time evolution of the F HB function and (ii) the total histograms of Figures 9 and 11 . In particular, this behavior can be related to the interactions involving the Oc and Hd1 atoms, which form stronger hydrogen bonds with solvent molecules.…”

“…Computation of the spectrum of the isolated molecule at a higher level of theory (B2PLYP in conjunction with the jun-cc-pVTZ basis set 39 at the CCSD(T)-F12/cc-pVDZ-F12 geometries reported in ref ( 35 )) has a negligible effect on the blue-side maximum but significantly improves the agreement between theory and experiment for the red-sideband. At this level, the difference between theory and experiment is comparable for both bands (4 and 6 nm, respectively) and also their relative heights are close to the experimental counterparts.…”

“…The first structural information related to the hydrogen bond interaction is retrieved by computing the pair radial distribution functions between creatinine atoms involved in hydrogen bonds with water molecules for both tautomers (see Figure 7 ). Although the average interaction between the creatinine tautomers with solvent is similar to that reported in the study by Léon at al., 35 the analysis of molecular dynamics trajectories provides not only structural, but also dynamical information.…”

Tautomeric Equilibrium in 1-Benzamidoisoquinoline Derivatives

“…However, the explicit inclusion of the solvent molecules forming hydrogen bonds with the solute, thus additionally stabilizing the electrostatic interaction or catalyzing the proton transfer process, proved vital in the case of tiny energetic differences, as observed in the present case. Such a microsolvation study is critical, particularly for solvents such as water, and is well recognized theoretically [ 19 , 20 , 23 , 24 , 25 , 26 , 27 ]. Nevertheless, systematic microsolvation studies for other solvents are scarce.…”

Toward Spectroscopic Accuracy for the Structures of Large Molecules at DFT Cost: Refinement and Extension of the Nano-LEGO Approach

“…3 However, the fast relaxation of some structures to more stable counterparts in the presence of low energy barriers and the photodissociation of some products can bias any direct thermochemical interpretation of the results provided by this technique. 4,5 Quantum chemical (QC) computations can be profitably used to solve this kind of problems, but the increasing dimensions of the molecules amenable to high-resolution spectroscopic studies and the need of characterizing several different structures (e.g., conformers or tautomers) 6,7 exacerbate the never ending fight between accuracy and feasibility. Furthermore, conventional local optimization techniques are very powerful for semirigid systems, but cannot be applied to the exploration of flat potential energy surfaces (PESs).…”