In this work, we meticulously report the first analysis of the three-dimensional structure of bicalutamide (BCL), a non-steroidal androgen receptor inhibitor, in supercritical carbon dioxide (scCO2). Our comprehensive approach integrates experimental data from nuclear Overhauser effect spectroscopy (NOESY) with calculated internuclear distances based on likely conformer structures, ensuring our findings' high accuracy. To minimize the influence of drifting state parameters (pressure and temperature) during the experiments, we applied a specially developed single-NOESY method, which enables the extraction of the required quantitative data from a NOESY spectrum. The results, which demonstrate the ratio of «open» to «closed» BCL conformers in scCO2 to be 24 % to 76 %, respectively, with an associated error of no more than 5 %, are a testament to the rigor and precision of our research. This work represents a step towards a comprehensive investigation of BCL’s structure in scCO2, thereby contributing to developing new pharmaceutical forms based on this compound.
