"CLASSIC NMR": an in-situ NMR strategy for mapping the time-evolution of crystallization processes by combined liquid-state and solid-state measurements.
Bottom Line: A new in-situ NMR strategy (termed CLASSIC NMR) for mapping the evolution of crystallization processes is reported, involving simultaneous measurement of both liquid-state and solid-state NMR spectra as a function of time.In particular, as crystallization proceeds (monitored by solid-state NMR), the solution state becomes more dilute, leading to changes in solution-state speciation and the modes of molecular aggregation in solution, which are monitored by liquid-state NMR.The CLASSIC NMR experiment is applied here to yield new insights into the crystallization of m-aminobenzoic acid.
Affiliation: School of Chemistry, Cardiff University, Cardiff CF10 3AT, Wales (UK).Show MeSH
Mentions: We now develop a more detailed interpretation of the changes in the liquid-state 13C NMR spectrum during crystallization. Figure 5 shows the 13C chemical shift δi(t) for each site (i) in m-ABA as a function of time relative to the corresponding initial value δistart. Initially, the system is a supersaturated solution10 (concentration ca. 1.4 times the solubility of Form III at 33 °C). After crystallization begins, the supersaturation decreases with time. By the end of the crystallization process, the system is an equilibrium saturated solution [chemical shifts denoted δieq(DMSO)]. To rationalize the changes in the solution state as crystallization proceeds, we consider values of Δδiclassic=δistart−δieq(DMSO), representing the difference in each chemical shift between the initial maximally supersaturated solution and the final equilibrium saturated solution. Values of Δδiclassic determined from the data in Figure 5 are given in Table 1.
Affiliation: School of Chemistry, Cardiff University, Cardiff CF10 3AT, Wales (UK).