The cleavage of indinavir sulfate: synthesis and characterization of a cis-1-amino-2-indanol salt.

Abstract

The HIV-1 protease inhibitor indinavir sulfate was cleaved via a one-pot reflux synthesis using 1-propanol, yielding the salt bis(2-hydroxy-2,3-dihydro-1H-inden-1-aminium) sulfate, 2C₉H₁₂NO⁺·SO₄^2-. Single-crystal X-ray diffraction (SC-XRD) revealed that the salt crystallizes in the monoclinic space group P2₁. The structure consists of two conformationally distinct cations and one sulfate anion, stabilized through an extensive hydrogen-bonding network. Thermal analysis showed minor solvent loss around 200 °C, followed by a two-step decomposition process commencing at 306.6 °C. Hirshfeld surface analysis revealed dominant O...H/H...O (44.4-41.0%) and H...H (45.2-40.1%) intermolecular contacts, with minor contributions from C...H/H...C and C...O/O...C interactions. These contact percentages were calculated for each of the two independent cations. The van der Waals surface area (687.30 Ų) accounts for 71.43% of the unit cell. These results provide structural and thermal evidence for the transformation of indinavir sulfate under alcoholytic conditions, highlighting the formation and stabilization of the resulting salt.