Theoretical analysis of lactone and carboxylate forms of camptothecin in aqueous solution: Electronic states, absorption spectra, and hydration

The vibronic absorption spectra of the camptothecin drug in an aqueous solution have been calculated for the first time. The calculations were carried out by the TD-DFT method. It was shown that both for lactone and carboxylate forms an excellent agreement with the experimental spectrum gives the BMK/6-31++G(d,p)/IEFPCM theory level. It was demonstrated that absorption spectra of both forms in the 300–400 nm wavelength range are due to single HOMO → LUMO (S0 → S1) electronic transition, and the short-wavelength smaller peak and shoulder are of vibronic origin. This result is at odds with the previous conclusions of other authors that this peak has a dimeric nature or is caused by interaction with an aqueous medium, and the shoulder is due to a separate electronic transition. According to my calculations, strong hydrogen bonds of the lactone and carboxylate forms with water molecules do not affect their absorption spectra. This is because some of these H-bonds were enhanced by photoexcitation of alkaloid molecules, while others were weakened. The opening of the lactone ring does not affect the position of the vibronic absorption bands but only leads to their significant broadening. Therefore, two separate maxima of the lactone form of the alkaloid merge into one broad peak. The absence of the influence of the lactone E ring on the absorption of the alkaloid is since the frontier orbitals are localized on other rings of the chromophore. Calculations have shown that the dipole moment of both forms of the alkaloid decreases significantly upon excitation. In combination with the practically zero contribution of specific interactions with an aqueous environment, this result indicates the n → π* type of the considered electronic transition. It agrees with both the experimental and theoretical results of some authors. Various characteristics of excited states of both drug forms (IR spectra, atomic charges, electron density, and electrostatic potential distributions) were obtained.