Molecular structure of vecuronium bromide, a neuromuscular blocking agent. Crystal structure, molecular mechanics and NMR investigations

The crystal and molecular structure of vecuronium bromide {1-[2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(piperidin-1-yl)androstan-16-yl]-1-methylpiperidinium bromide}, a potent non-depolarizing neuromuscular blocking agent, has been determined by single-crystal X-ray diffraction analysis. The compound crystallizes in the orthorhombic system, space group P212121. The observed axial conformation of the A ring acetoxy and piperidinyl substituents at positions 2 and 3 of the steroid skeleton is also present in solution, as is indicated by NMR experiments. After protonation of the piperidinyl group at position 2 this conformation changes into an equatorial conformation similar to the one observed in the N-methylated analogue pancuronium bromide. Molecular mechanics calculations have been performed to explain these observations.