Tautomeric Forms of 2-Thiobarbituric Acid As Studied in the Solid, in Polar Solutions, and on Gold Nanoparticles

Abstract

2-Thiobarbituric acid (TBA) coated gold nanoparticles (average diameter = 5.90 nm) were produced and studied by several experimental and theoretical methods. As part of this study, the molecular structure of TBA tautomers in the solid, in polar solutions, and adsorbed onto gold nanoparticles was studied. The resolution of this complicated system (10 possible isomers) was accomplished with the aid of experimental (IR, UV−vis, and NMR) and theoretical (DFT and MP2) methods. The general conclusion is that there are two preeminent isomers, N1 and N10, with different stabilities in different media. N1, the keto−thione tautomer, is the most stable in gas phase (ΔGo298 ≈ 8−9 kcal/mol lower than the second-most stable isomer, depending on the method of calculation used). However, experimental spectroscopic data supported by the theoretical calculations strongly suggest an equilibrium between the tautomers N1 and N10 in methanol solution, where enolization of one keto group is produced by proton transfer from the methylene group, which is more acidic than the NH groups. With the use of the polarizable continuum method for simulating solvents, N10 is predicted to be even more stable than N1 by ΔGo298 ≈ 1 kcal/mol in methanol. On the other hand, the IR spectrum of the solid can be best explained by assuming that only N10 is present, a fact also supported by the observation that the IR spectrum of TBA absorbed onto gold nanoparticles can be explained by a larger ratio of [N10]/[N1] than that present in methanolic solution. Isomerization of N1⇋ N10 can be explained by intervention of the solvent, proceeding faster in methanol solutions than in DMSO, where it is nevertheless observed after a time, according to the 13C NMR spectra. Our experiments support absorption of TBA onto gold nanoparticles through S−Au and N−Au interactions, with the preeminence of a N10-like enol structure. The experiments also demonstrate that the synthesized TBA-coated gold nanoparticles can autoassociate by hydrogen bonding to form larger structures. This same H-bonding capacity also assures that these coated nanoparticles act as thistles toward proteins in solution, binding them strongly, presumably not by chemical reaction but by a network of hydrogen bonds.