Polymorphism manifestations and aqueous environment influence on the physico-chemical properties of modified succinic acid

Abstract

Background and Objectives: Succinic acid is widely used in medicine, in particular, in the treatment of cardiological, neurological and endocrinological diseases. An urgent task of pharmacology is to increase the degree of bioavailability and solubility of drugs. One of ways to increase the therapeutic effect of drugs is the development of their polymorphic modifications, which contribute to a more pronounced therapeutic effect. One of ways to obtain new forms of succinic acid with better solubility and bioavailability is polymorphic modification nanotechnology based on the recrystallization of organic substances. We analyze the conformers and the influence of the aqueous environment on the physical-chemical properties of succinic acid. Materials and Methods: Spectral manifestations of modified succinic acid polymorphism and aqueous environment influence on spectral and energy characteristics are investigated on the integrated approach (experiment, theory) basis. The IR spectra of succinic acid are measured in the region of 600–4000 cm−1. The structures of an isolated molecule and a fragment of a chain associate of succinic acid conformers and their complexes with water are calculated using the density functional theory (DFT). The IR spectra and structures of complexes are calculated and compared with experimental data. The effect of hydrogen bonding on physical-chemical properties of succinic acid under recrystallization conditions is evaluated. Results: As a result of research, various succinic acid structures have been considered, as a result of which, by analyzing the energy difference, variants of conformers have been found both for one molecule and for the succinic acid dimer of the chain associate fragment. When water molecules are added, the characteristic peaks of the high-frequency region of the spectrum are shifted, that indicates the formation of hydrogen bonds. Conclusions: As a result of studies of the recrystallizated succinic acid physical-chemical properties a change in the crystal morphology has been detected based on the results of scanning electron microscopy. Water molecules, which remain in the structure of the modified molecular complex, have a great influence on the spectral characteristics of succinic acid. This has been discovered by comparing experimentally measured and calculated IR spectra of modified succinic acid. When water molecules are added to the conformers of an isolated molecule and a fragment of a chain associate of succinic acid, a shift of the characteristic peaks of the high-frequency spectral region corresponding to the valence vibrations of the O-H bond of the hydroxyl group of succinic acid is observed, that indicates the formation of hydrogen bonds. Analysis of interaction of succinic acid with water molecules indicates that during the preparation of polymorphic modifications, after the freeze-drying stage, water molecules are present in the modified succinic acid. In turn, the presence of the interaction of succinic acid with water molecules promotes stronger hydrogen bonding, that leads to a change in the physical-chemical properties of succinic acid.

Keywords

• succinic acid
• ir spectrum
• polymorphism
• molecular modeling
• density functional theory
• hydrogen bonds
• recrystallization