Solvates of Zwitterionic Rifampicin: Recurring Packing Motifs via Nonspecific Interactions

Abstract

Antibiotic rifampicin was recrystallized from solutions containing aliphatic alcohols, ketones, or dimethyl sulfoxide. Thirteen new solvates were obtained that were studied by X-ray crystallography. In these solvates rifampicin exists in a zwitterionic form. The reported solvates are classified into eight different structural types. Whereas rifampicin molecules in the solvates form diverse assemblies via hydrogen bonds, the recurring structural motif in these crystals is generated by nonspecific intermolecular interactions. This motif has the form of a periodic one-dimensional (1D) rod, and similar 1D motifs were found in the structures of other zwitterionic or ionic rifamycins. In rifampicin solvates, these rods form a basis for the construction of two types of two-dimensional (2D) periodic modules: monolayers found in six structural types of rifampicin solvates and bilayers observed in two types of solvates. Diverse mutual arrangements of these 2D modules lead to the formation of channels with accommodated solvent molecules that consist of 10–40% of the crystal volume. Differential thermal analysis/thermogravimetric analyses and powder X-ray diffraction show that desolvation of the rifampicin 2-propanol solvate results in polymorph II of rifampicin. We show here that solvate decomposition may be a route to transformation of a thermodynamically stable polymorphic form into a metastable one.

Specific Interactions between Rifamycin Antibiotics and Water Influencing Ability To Overcome Natural Cell Barriers and the Range of Antibacterial Potency

“…The analysis of these spectra introduces a new and important factor, namely, a water (35) groups are present, albeit, exclusively in the solid state. 29 The X-ray structure of the zwitterionic RMP solvate with MeOH (Figure 4b) reported here, which is unique relative to the earlier reported ones, 30,31 points to an alternative way of possible stabilization of the ansa-bridge conformations by water. In this structure, the hydroxyl group of MeOH is included in the collective system of H-bonds that starts at NH(lactam) and ends at the acetyl carbonyl, however, at the expense of N( 2 S1 and S2).…”

“…Bacchi et al showed earlier that water molecules stabilize the s -cis conformation of the diene fragment for nonionic rifamycin S (lacking C(3) substituent), where some cooperative interactions between O(1)­H, (O21)­H, O(23)­H, and OC(35) groups are present, albeit, exclusively in the solid state . The X-ray structure of the zwitterionic RMP solvate with MeOH (Figure b) reported here, which is unique relative to the earlier reported ones, , points to an alternative way of possible stabilization of the ansa -bridge conformations by water. In this structure, the hydroxyl group of MeOH is included in the collective system of H-bonds that starts at NH­(lactam) and ends at the acetyl carbonyl, however, at the expense of N(2)–H···N(38) intramolecular stabilization.…”

“…In contrast to RFB and RFX, in RFP and RMP solutions, Atype conformers were exclusively detected, irrespective of the solvent type. Furthermore, structures of RFP and RMP in solution and in many crystals 30,31 are strongly stabilized by the presence of an intramolecular H-bond N(2)−H•••N (38), which hinders free interconversion between A-and C-type conformers. Hence, for RMP and RFP, the possibility of ansabridge adaptation to the changing nature of the outer and inner cell membranes for Gram-negative bacteria is limited, which is further reflected in their narrower range of antibacterial potency, mainly against Gram-(+) strains.…”

Assessment of persistent antimicrobial and anti-biofilm activity of p-HEMA hydrogel loaded with rifampicin and cefixime

“…Moreover, because RIF is zwitterionic, it would act as anion at pH 9 leading to higher ionization and subsequent enhancement in water uptake. The observed elevation in EWC% at pH 9 in all tested films is due to the ionization of the hydroxyl group in p-HEMA that leads to enhance water uptake and entrapment 49 , 50 . The protonation of the primary alcohol groups in p-HEMA would result in ionic repulsion leading to expansion and increasing the probabilities of interaction with water.…”

Various Molecular Arrangements Leading to Different Desolvation Rates: Research on the Stability of 2,7‐Dibromo‐9H‐carbazole Solvates

“…[ 22 ] also studied the role of hydrogen bonds playing in the molecular self‐assembly process of sulfamethazine (SFZ) solvates and found that it was the mainly hydrogen bond that causes the self‐assembly of all four kinds of SFZ solvates. Although molecular stacking mode is also considered to be a factor that influences the stability of the solvates, [ 23–25 ] compared with the intermolecular interaction, research on the effect of stacking on the stability of solvates is still insufficient, and the study of the stacking mode could help us to further understand the stability of solvates.…”