Structural, energetic and spectroscopic characterisation of 5-fluorouracil anticarcinogenic drug isomers, tautomers and ions

ABSTRACT

In many cases, 5-fluorouracil (5-FU) is the first-line drug used in combined chemotherapy and radiotherapy treatments due to its radio-sensitization properties. It could participate in a tautomerization process similar to that of uracil, where 5-FU may couple to adenine in DNA. At present, we performed structural and spectroscopic studies using quantum chemical methods of neutral and cationic isolated 5-FU anticarcinogenic drug tautomers, either interacting with a water molecule or embedded into an implicit water solvent. Also, we determined the stationary points (both stable structures and transition states) on their ground potential energy surfaces playing a role during the tautomerization processes. For neutral and ionic species in the gas phase and in solvent, the ordering of the tautomers is found to be the same, where the di-keto form of 5-FU is the most stable structure, followed by the keto–enol and di-enol structural forms. The energy barriers for tautomerization are strongly reduced in solvent (< 0.5 eV) compared to isolated species (∼2 eV). The patterns of their lowest electronic states are also computed. Our data may help for the identification of these species in vivo and in the laboratory.

GRAPHICAL ABSTRACT

KEYWORDS:

• DFT computations
• spectroscopy
• halouracils
• anticarcinogenic drug
• tautomerism and ionised molecules

Acknowledgements

The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding the research through the Research Group Project No. RGP-333. We thank Dr. Roberto Linguerri (France) for his comments on the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding the research through the Research Group Project No. RGP-333.