Sildenafil–Resorcinol Cocrystal: XRPD Structure and DFT Calculations

Rafael Barbas,Rafel Prohens,Oriol Vallcorba,Antonio Frontera,Vineet Kumar

doi:10.3390/cryst10121126

Abstract

Herein, the X-ray powder diffraction (XRPD) crystal structure of a new Sildenafil cocrystal is reported, where resorcinol has been used as the coformer. The crystal structure has been solved by means of direct space methods used in combination with density functional theory (DFT) calculations. In the structure, the Sildenafil and resorcinol molecules form cooperative hydrogen bond (HB) and π-stacking interactions that have been analyzed using DFT calculations, the molecular electrostatic potential (MEP) surface, and noncovalent interaction plot (NCI plot). The formation of O–H⋯N H-bonds between resorcinol and Sildenafil increases the dipole moment and enhances the antiparallel π-stacking interaction.

Highlights

Sildenafil is a drug used in male patients with erectile dysfunction that acts by selectively inhibiting the cyclic guanosine monophosphate phosphodiesterase type 5 (Figure 1) [1,2]
The cocrystallization of Sildenafil with acetylsalicylic acid [7] and in the form of salicylate salt [8] has been used to mix a drug able to prevent strokes and myocardial infarctions with Sildenafil, which is not advised for patients with heart diseases
We focused this study on the analysis of the intermolecular H-bond between the resorcinol and Sildenafil molecules and its influence on the antiparallel stacking interaction between the pyrazolo[3,4-d]pyrimidine rings

Summary

Introduction

Sildenafil is a drug used in male patients with erectile dysfunction that acts by selectively inhibiting the cyclic guanosine monophosphate phosphodiesterase type 5 (Figure 1) [1,2]. The X-ray structures of Sildenafil and its citrate monohydrate salt have been previously reported [3,4]. The solid-state structure of many salts and cocrystals is available [5,6]. The cocrystallization of Sildenafil with acetylsalicylic acid [7] and in the form of salicylate salt [8] has been used to mix a drug able to prevent strokes and myocardial infarctions with Sildenafil, which is not advised for patients with heart diseases. We have previously discovered and analyzed, through a combined virtual/experimental cocrystal screen, new hybrid salt–cocrystal forms of Sildenafil [9].

Methods

Results

Conclusion