X-ray Raman scattering: a newin situprobe of molecular structure during nucleation and crystallization from liquid solutions

Abstract

X-ray Raman scattering (XRS) has been used for in situ probing of solute molecule speciation in solution during cooling crystallization.

Imidazole in Aqueous Solution: Hydrogen Bond Interactions and Structural Reorganization with Concentration

“…The introduction in the improved model of a negatively charged extra point along the bisector of the CNC angle, accounting for the LP on the N3 nitrogen atom, allows to describe the imidazole–water hydrogen bond interaction in solution in good agreement with the CPMD counterpart. Remarkably the improved model faithfully reproduces the SDF for the N3–OW pair interaction observed in the ab initio simulations, exhibiting the expected preferential orientation of the N3–OW hydrogen bond along the bisector of the CNC angle due to N3 sp 2 hybridization. , To our knowledge, no other available classical potential model for imidazole, based on the fixed atomic charges paradigm, can produce a correct spatial orientation of the N3–OW directional hydrogen bond in the plane of the imidazole ring. As shown in ref for the OPLS and CHARMM potential model, in ref for the GAFF/AMBER potential model, and in the present study for the GAFF2/AMBER force field, all these standard models significantly overestimate the probability of the perpendicular H-π bond in water–imidazole interactions.…”

“…Remarkably the improved model faithfully reproduces the SDF for the N3−OW pair interaction observed in the ab initio simulations, exhibiting the expected preferential orientation of the N3−OW hydrogen bond along the bisector of the CNC angle due to N3 sp 2 hybridization. 7,13 To our knowledge, no other available classical potential model for imidazole, based on the fixed atomic charges paradigm, can produce a correct spatial orientation of the N3−OW directional hydrogen bond in the plane of the imidazole ring. As shown in ref 7 for the OPLS and CHARMM potential model, in ref 15 for the GAFF/AMBER potential model, and in the present study for the GAFF2/ AMBER force field, all these standard models significantly overestimate the probability of the perpendicular H-π bond in water−imidazole interactions.…”

“…"Molecule speciation" during imidazole crystallisation from supersaturated aqueous solution was studied recently using X-ray Raman scattering (XRS). 13 Near-edge X-ray absorption fine structure (NEXAFS) has been also employed recently 14 as a probe for imidazoleimidazole self-association in a series of samples where the heterocyclic compound concentration was varied from ∼0.5 M to ∼8 M. Negligible changes are observed in the C and N K-edge XRS spectra during cooling, indicating that the average solvation structure around imidazole molecules does not change significantly while traversing the thermodynamically metastable supersaturated liquid phase until the onset of crystallisation. These results are consistent with those obtained by NEXAFS experiments 14 where it has been observed that the NEX-AFS signal does not appreciably change with concentration, while the spectra of species in solution substantially differ from those of imidazole monomers in gas phase.…”

X-ray Raman Scattering: A Hard X-ray Probe of Complex Organic Systems

“…The last two decades have seen the rapid development of XRS-based research for the study of low-energy edge transitions for a variety of organic materials, − liquid systems − including water-based systems, − gases, − and crystals. ,− XRS has been also employed to access transitions beyond the dipole limit (i.e., multipole transitions) in light elements, − lanthanides, − and actinides. − Following the pioneering work by Mao et al, a considerable amount of work has been published on the in situ characterization of materials under high pressure via XRS, in which the samples under study are enclosed by diamond anvil cells and a gasket material. The goal of high pressure XRS studies is to probe variations in the bonding characteristics, orbital hybridization, oxidation state, and spin state to understand the local atomic structure and/or the changes of electronic structure of the materials under study .…”

Time-Resolved X-ray Phase-Contrast Imaging (XPCI) of Nucleation and Crystal Growth in the Anti-Solvent Crystallization of Lovastatin

“…6,8,9 However, experimental unravelling of the molecular basis of these nucleation processes (and indeed also of more recently alternative molecular pathways 2,3,8,10,11 ) faces a fundamental challenge, namely that nucleation events are rare and stochastic in time and space. To an extent, localization of homogeneous events by, e.g, use of liquid-liquid interfaces 9 and droplets [12][13][14] has been used to overcome the spatial challenge, enabling time-resolved monitoring of structure and composition by X-ray absorption, 9,15,16 Raman 14,17 and UV/Vis spectroscopy, 17,18 SAXS 18,19 and XRD/WAXS. 13,18 However, localization is associated with confinement in small volumes, and is often introducing some degree of heterogeneity, which influences observable nucleation behavior.…”