Abiraterone Acetate Complexes with Biometals: Synthesis, Characterization in Solid and Solution, and the Nature of Chemical Bonding

Abstract

Abiraterone acetate (AbirAc) is the most used steroidal therapeutic agent for treatment of prostate cancer. The mainly hydrophobic molecular surface of AbirAc results in its poor solubility and plays an important role for retention of abiraterone in the cavity of the receptor formed by peptide chains and heme fragments. In order to evaluate the hydrolytic stability of AbirAc, to modify its solubility by formation of new solid forms and to model bonding of this medication with the heme, a series of d-metal complexes with AbirAc was obtained. AbirAc remains stable in water, acetonitrile, tetrahydrofuran, and ethanol, and readily interacts with dications as a terminal ligand to create discrete complexes, including [FePC(AbirAc)2] and [ZnTPP(AbirAc)] (H2PC = phthalocyanine and H2TPP = 5,10,15,20-tetraphenylporphyrine) models for ligand–receptor bonding. In reactions with silver(I) nitrate, AbirAc acts as a bridge ligand. Energies of chemical bonding between AbirAc and these cations vary from 97 to 235 kJ mol−1 and exceed those between metal atoms and water molecules. This can be indicative of the ability of abiraterone to replace solvent molecules in the coordination sphere of biometals in living cells, although the model [ZnTPP] complex remains stable in CDCl3, CD2Cl2, and 1,1,2,2-tetrachloroethane-d2 solvents and decomposes in polar dimethylsulfoxide-d6 and methanol-d4 solvents, as follows from the 1H DOSY spectra. Dynamics of its behavior in 1,1,2,2-tetrachloroethane-d2 were studied by ROESY and NMR spectra.

Sumatriptan Succinate Hemi(Ethanol Solvate)

“…This information is required for phase identification and purity control. In our study of novel solid forms of known active pharmaceutical ingredients [7][8][9], the ability of sumatriptan succinate to form various solvates was examined. Recrystallization from ethanol afforded a hemisolvate, HSum + •HSucc − •0.5EtOH (1).…”

9-Ethyl-6,6-Dimethyl-8-[4-(Morpholin-4-Yl)piperidin-1-Yl]-11-Oxo-6,11-Dihydro-5H-Benzo[b]carbazole-3-Carbonitrile Hydrochloride

“…Within our research study of crystal and molecular structures of solid forms of active pharmaceutical ingredients [5][6][7][8][9] powder pattern of alectinib hydrochloride was measured using CuKα radiation. Room temperature was used to overcome effects of thermal contraction and to escape possible phase transitions.…”