A DFT Study of Functionalization of Anti-retroviral Drugs by Fluorescence Markers

BRASCA R; FABIAN; GOICOECHEA

Congreso; CESTC2013; 2013

A computational study [B3LYP/6-31G(d) including dispersion corrections and M06-2X/6- 311+G(2df,2p)] of some chemical reactions between pharmaceutical drugs (zidovudine, stavudine) and fluorescent reagents, e.g. 1-naphthylisocyanate (NIC) and N-methylisatoic anhydride (NMIA) was performed. The mechanistic details and energetic profiles of the derivatization reactions were analyzed in order to choose the appropriate reagents in view of its use in experimental reactions. The anti-retroviral drugs investigated have different kind of nucleophilic sites (i.e. amino and alcohol functional groups) in their structures, which can lead to the formation of different derivatization products (i.e. carbamate/urea for the reactions with NIC and amide/ester for the case of NMIA). Therefore, three possible reaction paths were considered for the reactions with NIC and two paths for the reactions with NMIA. Reaction of