Intramolecular hydrogen bond in biologically active o-carbonyl hydroquinones.

Maximiliano Martínez-Cifuentes,Boris Weiss-López,Ramiro Araya-Maturana,Leonardo Santos

doi:10.3390/molecules19079354

Maximiliano Martínez-Cifuentes, Boris Weiss-López + Show 2 more

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https://doi.org/10.3390/molecules19079354

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Abstract

Intramolecular hydrogen bonds (IHBs) play a central role in the molecular structure, chemical reactivity and interactions of biologically active molecules. Here, we study the IHBs of seven related o-carbonyl hydroquinones and one structurally-related aromatic lactone, some of which have shown anticancer and antioxidant activity. Experimental NMR data were correlated with theoretical calculations at the DFT and ab initio levels. Natural bond orbital (NBO) and molecular electrostatic potential (MEP) calculations were used to study the electronic characteristics of these IHB. As expected, our results show that NBO calculations are better than MEP to describe the strength of the IHBs. NBO energies (∆Eij(2)) show that the main contributions to energy stabilization correspond to LP→σ* interactions for IHBs, O1…O2-H2 and the delocalization LP→π* for O2-C2 = Cα(β). For the O1…O2-H2 interaction, the values of ∆Eij(2) can be attributed to the difference in the overlap ability between orbitals i and j (Fij), instead of the energy difference between them. The large energy for the LP O2→π* C2 = Cα(β) interaction in the compounds 9-Hydroxy-5-oxo-4,8, 8-trimethyl-l,9(8H)-anthracenecarbolactone (VIII) and 9,10-dihydroxy-4,4-dimethylanthracen-1(4H)-one (VII) (55.49 and 60.70 kcal/mol, respectively) when compared with the remaining molecules (all less than 50 kcal/mol), suggests that the IHBs in VIII and VII are strongly resonance assisted.

Highlights

Hydroquinones (HQ) and their oxidized form, quinones (Q), constitute a biologically relevant redox pair
P-hydroquinone is more stable than p-quinone, usually substituted p-hydroquinones (p-HQ) are thermodynamically less stable than substituted p-quinones (p-Q), but p-Q can be effectively transformed into p-HQ by several mechanisms in biological systems [7], and they can co-exist inside living organisms
Recent electrochemical study about quinones possessing intramolecular hydrogen bonds (IHBs) shows that this interaction stabilizes the anion radical structure, leading to a shift in reduction potentials toward less negative values when compared with quinones without IHBs [11]

Summary

Introduction

Hydroquinones (HQ) and their oxidized form, quinones (Q), constitute a biologically relevant redox pair. The biological activity of hydroquinones has been related to their capability to lose an electron followed by deprotonation (or alternatively lose a hydrogen atom), to afford the corresponding semiquinone radical. These intermediates have been associated to biological properties, such as pro-oxidant activity, by interacting with several intracellular molecules, such as DNA and proteins. Modulation of the electron-transfer capability is very important for the biological activity of quinones and hydroquinones. A recent electrochemical study about quinones possessing intramolecular hydrogen bonds (IHBs) shows that this interaction stabilizes the anion radical structure, leading to a shift in reduction potentials toward less negative values when compared with quinones without IHBs [11]. IHBs have shown appreciable effects on the antioxidant properties of hydroquinones and related phenols [12,13]

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