Understanding Photostability of Biomolecules Using Multi-Reference Quantum Chemical Methods

Abstract

Photostability is the property of a molecule to not chemically react when excited with light. This is a prerequisite for the origin and preservation of life since the ambient environment has ample radiation from the sun, which can be potentially damaging. Here, we have studied the photodecay mechanisms of two biologically relevant molecules: 5,6-dihydroxyindole (DHI) and barbituric acid (BA). Our approach involves obtaining pathways on the excited state potential energy surfaces for deactivation, which usually involve bond stretched geometries and points of degeneracy like conical intersections (CIs). Such calculations require multi-reference electronic structure methods and accordingly we have used the complete active space self-consistent field (CASSCF) approach and its extensions. Unlike other commonly used electronic structure methods, these require significant user input based on chemical intuition for an accurate description of excited state processes. DHI is a monomeric unit of eumelanin, a natural sunscreen present in human skin. Assuming that DHI photophysics will be reflective of eumelanin photophysics, a bottom-up approach has been employed to study its photophysics. Experiments on DHI show excitation energy dependent fluorescence kinetics and our study reveals the reason for this. We found two planar and one non-planar CIs through which photodecay of the excited state can take place. Accessing these CIs require the molecule to overcome energy barriers, which is possible when the initial excitation is to higher vibrational states of the excited electronic states. Thus, higher energy leads to shorter excited state lifetimes. This result is significantly different from earlier results obtained with single- reference methods. Our study also shows that isolated monomeric DHI cannot explain the ultrafast deactivation of eumelanin. BA is proposed to be a prebiotic nucleobase which played a role in the emergence of RNA-based life. For BA to be a candidate for proto-RNA, it must have been photostable to survive the intense UV radiation present at the time when the ozone layer was absent. BA can exist as two tautomers: keto and enol. Theoretical calculations on isolated BA predict that the keto tautomer is more stable than enol. However, recent reports have shown that crystalline BA exists in the enol form. We have explored the relative stability of this molecule in the aqueous environment. Our quantum calculations on BA-water clusters, where the clusters were chosen systematically using a molecular dynamics based scheme, show that the enol tautomer gets stabilized more than the keto tautomer due to solvation. Recently, transient absorption experiments on BA have explored its photodecay dynamics. Our calculated photodecay pathways of BA help in interpreting these experiments. Further, we also compare the photodecay dynamics of BA with that of Uracil, a canonical RNA nucleobase, and find that despite strong structural similarities, the two molecules follow different photodecay pathways.