An analysis of the experimental and theoretical charge density distributions of the piroxicam–saccharin co-crystal and its constituents

Abstract

Experimental and theoretical charge density analyses of piroxicam (1), saccharin (2) and their 1:1 co-crystal complex (3) have been carried out. Electron density distribution (EDD) was determined through the use of high-resolution single crystal X-ray diffraction and the data were modelled using the conventional multipole model of electron density according to the Hansen-Coppens formalism. A method for optimising the core density refinement of sulfur atoms is discussed, with emphasis on the reduction of residual electron density that is typically associated with this atom. The asymmetric unit of complex (3) contains single molecules of saccharin and the zwitterionic form of piroxicam. These are held together by weak interactions (hydrogen bonds, π-π and van der Waals interactions), ranging in strength from 4 to 160 kJmol -1 , working together to stabilise the complex;. analysis of the molecular electrostatic potential (MEP) of the complexes showed electron redistribution within the cocrystal, facilitating the formation of these generally weak interactions. Interestingly, in the zwitterionic form of piroxicam, the charge distribution reveals that the positive and negative charges are not associated with the formal charges normally associated with this description, but are distributed over adjacent molecular fragments. The use of anisotropic displacement parameters (ADPs) for hydrogen atoms in the multipole model was also investigated but no improvement in the quality of the topological analysis was found.3

Experimental Electron Density Distribution in Two Cocrystals of Betaines with p-Hydroxybenzoic Acid

“…a b In the case of betaine zwitterions, the atomic charge distributions are one of the most interesting issues; consequently, the partition of the charge between the quaternary ammonium and the carboxylate groups was also analyzed. To some extent, surprisingly, the charges reflect rather non-zwitterionic nature of TRG and MPB, since the positive charge is not concentrated at the nitrogen (q(N) = −0.81 e for 1 and q(N) = −0.74 e for 2), but is rather delocalized over the ring (similar effect has been observed in experimental charge density studies previously [24]). In the case of betaine zwitterions, the atomic charge distributions are one of the most interesting issues; consequently, the partition of the charge between the quaternary ammonium and the carboxylate groups was also analyzed.…”

Structure and electrostatic properties of the pyrimethamine–3,5-dihydroxybenzoic acid cocrystal in water solvent studied using transferred electron-density parameters

“…Moreover, according to Cramer & Kraka (1984), the corresponding negative value (V cp = À123.35) meets the criteria to be called a partially covalent interaction. Such a strong interaction has been reported in the literature; see, for eaxmple, Du et al (2016). The O3-H3CÁ Á ÁO6 viii hydrogen bond is somewhat weak compared to the interaction mentioned above.…”

OPTICS: Operant Probability Theory in Crystal Solutions, Application of ssNMR, and Probability Theory in Polymorph Identification

“…Piroxicam is a nonsteroidal anti-inflammatory drug used in the treatment of arthritis. The polymorphism of piroxicam (Figure a) has been widely studied yielding crystal structures for eight anhydrous forms. ,− Herein, we analyze four solid forms of piroxicam, namely, piroxicam I (CSD ID: BITSEH13), piroxicam II (CSD-ID: BIYSEH05), piroxicam III (CSD-ID: BIYSEH07), and piroxicam IV (CSD-ID: BIYSEH08) . Piroxicam II and IV are closely related crystal forms, as seen in the experimental XRPD patterns in Figure b.…”