High-throughput macromolecular polymorph screening via an NMR and X-ray powder diffraction synergistic approach: the case of human insulin co-crystallized with resorcinol derivatives was written by Spiliopoulou, Maria;Valmas, Alexandros;Triandafillidis, Dimitris-Panagiotis;Fili, Stavroula;Christopoulou, Magdalini;Filopoulou, Aikaterini J.;Piskopou, Anastasia;Papadea, Polyxeni;Fitch, Andrew N.;Beckers, Detlef;Degen, Thomas;Gozzo, Fabia;Morin, Mickael;Reinle-Schmitt, Mathilde L.;Karavassili, Fotini;Rosmaraki, Eleftheria;Chasapis, Christos T.;Margiolaki, Irene. And the article was included in Journal of Applied Crystallography in 2021.Formula: C6H5ClO2 The following contents are mentioned in the article:
Regular injections of insulin provide life-saving benefits to millions of diabetics. Apart from native insulin and insulin analog formulations, microcrystalline insulin suspensions are also com. available. The onset of action of the currently available basal insulins relies on the slow dissociation of insulin hexamers in the s.c. space due to the strong binding of small organic ligands. With the aim of identifying insulin-ligand complexes with enhanced pharmacokinetic and pharmacodynamic profiles, the binding affinity of two resorcinol-based mols. (4-chlororesorcinol and 4-bromoresorcinol) and the structural characteristics of insulin upon co-crystallization with them were investigated in the present study. ‘In solution’ measurements were performed via saturation transfer difference (STD) NMR. Co-crystallization upon pH variation resulted in the production of polycrystalline precipitates, whose structural characteristics (i.e. unit-cell symmetry and dimension) were assessed. In both cases, different polymorphs (four and three, resp.) of monoclinic symmetry (P21 and C2 space groups) were identified via X-ray powder diffraction. The results demonstrate the efficiency of a new approach that combines spectroscopy and diffraction techniques and provides an innovative alternative for high-throughput examination of insulin and other therapeutic proteins. This study involved multiple reactions and reactants, such as 4-Chlororesorcinol (cas: 95-88-5Formula: C6H5ClO2).
4-Chlororesorcinol (cas: 95-88-5) belongs to organic chlorides. Organochlorines are organic compounds having multiple chlorine atoms. They were the first synthetic pesticides that were used in agriculture. They are resistant to most microbial and chemical degradations. Alkyl chlorides readily react with amines to give substituted amines. Alkyl chlorides are substituted by softer halides such as the iodide in the Finkelstein reaction.Formula: C6H5ClO2
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics