Crystal structures, Hirshfeld surface analysis and PIXEL energy calculations of three trifluoromethylquinoline derivatives: further analyses of fluorine close contacts in trifluoromethylated derivatives

摘要

As many studies have revealed, the introduction of a CF3 group into an organic compound can result in significant enhancement of biological activity. Factors which lead to this enhancement are thus of great interest. To investigate further this area, we have looked at the ability of fluorine to form close contacts with various atoms in organic compounds, e.g. F center dot center dot center dot F, F center dot center dot center dot O/O center dot center dot center dot F, F center dot center dot center dot C/C center dot center dot center dot F, H center dot center dot center dot F/F center dot center dot center dot H and F center dot center dot center dot N/N center dot center dot center dot F, as indicated from crystal structure determinations and Hirshfeld analysis studies on trifluoromethylated compounds. Herein we first report the crystal structures, Hirshfeld surface analyses (HSA), and PIXEL energy calculations of three trifluoromethylated quinoline derivatives, namely 2-(trifluoromethyl) quinolin-4-ol, 1, 4-ethoxy-2-(trifluoromethyl)quinoline, 2, and N-1-(2,8-bis(trifluoromethyl)quinolin-4-yl)ethane-1,2-diamine, 3. Of particular interest is the determination of the various fluorine. atom close contacts. The total percentages of fluorine. -atom close contacts in compounds 1-3 were determined to be high at 47, 41.2 and 60.7%, respectively. As relatively few HSA studies on trifluoromethylated compounds have reported the percentages of individual atom atom close contacts, we have also determined the percentages of atom center dot center dot center dot atom close contacts for 20 more trifluoromethylated compounds: the range of total fluorine center dot center dot center dot atom close contacts for these compounds was 20-60%. While these data are based on connections between similar molecules in a crystalline state, they also clearly suggest that a compound containing CF3 group(s) has the potential to make extensive intermolecular connections/close contacts with organic material. Thus a possible factor for the enhanced biological activity of a compound bearing CF3 group(s) could be the propensity of the CF3 group to form many close contacts, thereby aiding binding or interaction with a biological target.