Novel crystalline phase and first-order phase transitions of human insulin complexed with two distinct phenol derivatives

Abstract

The primary focus of the present work is the study of the effects that two ligands and the crystallization pH have on the crystalline forms of human insulin. For this purpose, human insulin (HI) was co-crystallized with two distinct phenolic derivatives: the organic ligands meta-cresol (m-cresol) and 4-nitrophenol. The formation of polycrystalline precipitates was then followed by means of structural characterization of the individual specimens in terms of unit-cell symmetry and parameters. In both cases, two different polymorphs were identified via X-ray powder diffraction measurements, the first of hexagonal symmetry (R3 space group) at higher pH values and the second of monoclinic symmetry (space group P21) with unit-cell parameters a = 87.4282 (5), b = 70.5020 (3), c = 48.3180 (4) Å, β = 106.8958 (4)°, the latter of which to our knowledge has never been observed before.

In Quest for Improved Drugs against Diabetes: The Added Value of X-ray Powder Diffraction Methods

“…(Figure 10). These crystalline polymorphs had been identified earlier by XRPD [29,56]. Diffraction profiles acquired for the P2 1(γ) polycrystalline samples extended to a resolution of~6.5 Å, whereas the lower resolution range for the P2 1(α) polycrystalline samples (~112-12 Å) was sufficient for successful indexing and Pawley analysis.…”

Applications of X-ray Powder Diffraction in Protein Crystallography and Drug Screening

“…An important feature of crystalline matter for pharmaceutical industries towards drug development is polymorphism, meaning the ability of a molecule or compound to exist in one or more molecular as well as crystalline phases [98]. Variation in the crystallization conditions like solvent polarity, initial macromolecular concentration, and precipitant agents may result in different crystal and/or molecular polymorphs [30][31][32]99].…”

“…T stands for an extended, R f for a "frayed" intermediate and R for a helical conformation, while the subscript is indicative of the number of monomers that exhibit the aforementioned arrangement [120]. Phenolic or non-phenolic organic molecules that can act as ligands have been used in HI co-crystallization experiments, resulting in a diverse assortment of polymorphs [30][31][32]98,[120][121][122].…”

“…Owing to the simplicity of the XRPD data collection process and the sensitivity of the method, since each polymorph reveals a unique pattern, the technique has become a robust tool for thorough examination of a wide range of microcrystalline precipitates [23,25]. Screening of crystalline polymorphism [30][31][32] is a very important step in the structural characterization of molecules of pharmaceutical interest as different crystalline polymorphs are often associated with modified physicochemical properties and/or biological activity. A pharmaceutical composition may consist of more than one component, each of which is an active pharmaceutical ingredient [33].…”

Structural, thermal and optical investigation of tin sulfide nanoparticles for next-generation photovoltaic applications

“…01-083-1758. The pattern was fitted using X'Pert High Score software [21] and other lattice parameters were determined. The lattice parameter of the nanoparticles was determined by a well-known Bragg relation: nλ = 2d sin θ (1) and the relation:…”