Computational Study of Electronic Effects from β-Substituents on the Tautomerism of Naphthazarin Derivatives

Abstract

In this work, semi-empirical AM1 and DFT B3LYP/6-31G** calculations were applied in the study of the interconversion among tautomers of several naphthazarin and 5-amino-8-hydroxy-1,4-naphthoquinone β-substituted derivatives bearing electron-donor or electron-withdrawing groups. Using a semi-empirical method, detailed potential energy landscapes for proton transfers were built, from which four tautomers and four transition states of interconversions were identified for each compound. These structures were recalculated without restraints and, using the Boltzmann distribution, the populations for each of the four tautomers and their respective molar fractions were calculated. The calculations showed that the tautomeric equilibrium is shifted to the tautomer where the ring with the substituent has a quinonic nature and is more pronounced when the β-substituent is an electron donor group. For derivatives of 5-amino-8-hydroxy-1,4-naphthoquinone, an equilibrium between an aromatic and a 1,5-naphthoquinonic non-aromatic enamine was observed, being the former the most stable.Keywords: tautomerism, B3LYP, AM1, molecular modeling, electronic effect IntroductionNaphthoquinones belong to a large class of natural and synthetic compounds. These compounds are frequently found in plants and on a smaller scale in inferior animals, exhibiting a broad scope of applications, such as drugs and dyes.1-9 5,8-Dihydroxy-1,4-naphthoquinone (1), naphthazarin, and its derivatives are particularly important due to their biological and pharmacological activities [10][11][12][13][14][15] and versatility as intermediates in the synthesis of more diversified chemical structures. 9,[16][17][18][19][20][21][22][23][24] One of their features is the presence of tautomerism. 12,25The tautomeric equilibrium changes their reactivity and spectroscopic properties. 16,18,20 Therefore, a systematic investigation of dihydroxy-1,4-naphthoquinones tautomerism can contribute to the understanding of their chemical reactivity, pharmacological activity, and spectroscopic characteristics. Despite being a quite simple concept, tautomerism is a phenomenon that still arises interest and has been the aim of several recent studies due to its great importance to organic and medicinal chemistry, biochemistry, pharmacology and molecular biology. 26 In many cases, the biological activity of a molecule or its reaction mechanism with biological receptors is strongly dependent on the tautomerism. However, experimental studies involving tautomerism are very difficult due to the fast reaction rate of these processes. Naphthazarin (1) and its derivatives are able of hydrogen transfer from the hydroxyl to the syn periplanar carbonyl groups. For each derivative, four tautomers can be drawn (Scheme 1). 27Glazunov and Berdyshev 28 studied the effect from mono to tetrachloro substitution on naphthazarin using DFT B3LYP/6-31G**. Their results showed that the strength of the intramolecular H-bond increases when the chlorine β-substitution is near to hydroxyl groups, but decreases in th...

Theoretical Insights Into the Excited State Double Proton Transfer Mechanism of Deep Red Pigment Alkannin

“…And they inferred the excited state single proton transfer process exists in the first excited (S 1 ) state along with hydrogen bond O1–H2···O3 . Then as mentioned by Serdiuk and co-workers, there are not enough subsequent reports about its excited state process, and people mainly focus on its dye applications and its derivatives. , In fact, it is well-known that the Franck–Condon ESIPT curves are too rough to clarify excited state behavior. And previous papers on alkannin do not attach importance to differences of excited state mechanisms arising from solvent effects.…”