Myelography Iodinated Contrast Media. 2. Conformational Versatility of Iopamidol in the Solid State

Abstract

The phenomenon of polymorphism is of great relevance in pharmaceutics, since different polymorphs have different physicochemical properties, e.g., solubility, hence, bioavailability. Coupling diffractometric and spectroscopic experiments with thermodynamic analysis and computational work opens to a methodological approach which provides information on both structure and dynamics in the solid as well as in solution. The present work reports on the conformational changes in crystalline iopamidol, which is characterized by atropisomerism, a phenomenon that influences both the solution properties and the distinct crystal phases. The conformation of iopamidol is discussed for three different crystal phases. In the anhydrous and monohydrate crystal forms, iopamidol molecules display a syn conformation of the long branches stemming out from the triiodobenzene ring, while in the pentahydrate phase the anti conformation is found. IR and Raman spectroscopic studies carried out on the three crystal forms, jointly with quantum chemical computations, revealed that the markedly different spectral features can be specifically attributed to the different molecular conformations. Our results on the conformational versatility of iopamidol in different crystalline phases, linking structural and spectroscopic evidence for the solution state and the solid forms, provide a definite protocol for grasping the signals that can be taken as conformational markers. This is the first step for understanding the crystallization mechanism occurring in supersaturated solution of iopamidol molecules.

Adsorptive Recovery of Iopamidol from Aqueous Solution and Parallel Reuse of Activated Carbon: Batch and Flow Study

“…At the same time, new bands were detected in IOP-loaded CPAC at 1050 and 3300 cm –1 , and these were assigned to the C–O and O–H/N–H stretching modes of the IOP molecule, respectively (Table S1 and Figure b). These absorption bands for the IOP compound were also observed by Bellich et al, confirming that IOP was effectively adsorbed onto CPAC. On the basis of this study, we can propose that the CO of different functional groups on the CPAC surface are the sites that interact with the IOP molecule.…”

Packing and Conformational Polymorphism in 1,2-Bis(aminocarbonyl(1-tert-butyl-1H-pyrazol-(3)5-yl))ethanes: Illuminating Examples of Highly Flexible Molecules

“…Notably, amide-containing compounds are of great biological and synthetic importance and have attracted attention in crystal engineering mainly due to the directionality of their strong N–H···OC interactions, which favor bonds adjusting and controlling the molecular assemblies. This anchoring site significantly influences an increasing number of polymorphs, , and the appeal in understanding interactions ranges from small organic molecules to macromolecules. , Furthermore, substituent effects and steric hindrance have also been shown to affect the packing of these compounds with amides, , and numerous studies have sought to enhance the aqueous solubility and investigate polymorphism control, dissolution, solubility, chirality-dependent supramolecular synthons, occurrence of concomitant polymorphs and desmotropy, and influence of the solvent in obtaining specific polymorphs. , …”

Theoretical B3LYP Study on Electronic Structure of Contrast Agent Iopamidol

“…IR and Raman spectroscopic studies, conducted in conjunction with quantum chemical calculations on three crystal forms, revealed that distinctly different spectral properties can be attributed, in particular, to different molecular structures. 10 The Density Functional Theory (DFT) calculations eventually lead to a good understanding of molecular properties and a detail of the molecular characteristics and interactions. 8 Thermodynamic properties such as enthalpy, entropy, and Gibbs free energy are important to understand the stability of molecules at different temperatures and pressures, which can be easily explained using DFT with the Gaussian 03 program.…”