New in situ solid-state NMR techniques for probing the evolution of crystallization processes: pre-nucleation, nucleation and growth.

The application of in situ techniques for investigating crystallization processes promises to yield significant new insights into fundamental aspects of crystallization science. With this motivation, we recently developed a new in situ solid-state NMR technique that exploits the ability of NMR to selectively detect the solid phase in heterogeneous solid-liquid systems (of the type that exist during crystallization from solution), with the liquid phase "invisible" to the measurement. As a consequence, the technique allows the first solid particles produced during crystallization to be observed and identified, and allows the evolution of different solid phases (e.g., polymorphs) present during the crystallization process to be monitored as a function of time. This in situ solid-state NMR strategy has been demonstrated to be a powerful approach for establishing the sequence of solid phases produced during crystallization and for the discovery of new polymorphs. The most recent advance of the in situ NMR methodology has been the development of a strategy (named "CLASSIC NMR") that allows both solid-state NMR and liquid-state NMR spectra to be measured (essentially simultaneously) during the crystallization process, yielding information on the complementary changes that occur in both the solid and liquid phases as a function of time. In this article, we present new results that highlight the application of our in situ NMR techniques to successfully unravel different aspects of crystallization processes, focusing on: (i) the application of a CLASSIC NMR approach to monitor competitive inclusion processes in solid urea inclusion compounds, (ii) exploiting liquid-state NMR to gain insights into co-crystal formation between benzoic acid and pentafluorobenzoic acid, and (iii) applications of in situ solid-state NMR for the discovery of new solid forms of trimethylphosphine oxide and L-phenylalanine. Finally, the article discusses a number of important fundamental issues relating to practical aspects, the interpretation of results and the future scope of these techniques, including: (i) an assessment of the smallest size of solid particle that can be detected in in situ solid-state NMR studies of crystallization, (ii) an appraisal of whether the rapid sample spinning required by the NMR measurement technique may actually influence or perturb the crystallization behaviour, and (iii) a discussion of factors that influence the sensitivity and time-resolution of in situ solid-state NMR experiments.

Significant modification of the I(-)3 Lewis base character in the ß-cyclodextrin polyiodide inclusion complex with Co2+ ion: an FT-Raman investigation.

The ß-cyclodextrin (ß-CD) polyiodide inclusion complex (ß-CD)(2)·Co(0.5)·I(7)·21H(2)O has been synthesized, characterized and further investigated via FT-Raman spectroscopy in the temperature range of 30-120°C. The experimental results point to the coexistence of I(-)(7) units (I(2)·I(-)(3)·I(2)) that seem not to interact with the Co(2+) ions and I(-)(7) units that display such interactions. The former units exhibit a disorder-order transition of both their I(2) molecules above 60°C due to a symmetric charge-transfer interaction with the central I(-)(3) [I(2)←I(-)(3)→I(2)], whereas in the latter units only one of the two I(2) molecules becomes well-ordered above 30°C. The other I(2) molecule remains disordered presenting no charge-transfer phenomena. The Co(2+) ion induces a considerable asymmetry on the geometry of the I(-)(3) anion and a significant modification of its Lewis base character. Complementary dielectric measurements suggest no important involvement of H···I contacts in the observed modification of the I(-)(3) electron-transfer properties.

Metal-heptaiodide interactions in cyclomaltoheptaose (beta-cyclodextrin) polyiodide complexes as detected via Raman spectroscopy.

The Raman spectra of the cyclomaltoheptaose (beta-cyclodextrin, beta-CD) polyiodide complexes (beta-CD)(2).NaI(7).12H(2)O, (beta-CD)(2).RbI(7).18H(2)O, (beta-CD)(2).SrI(7).17H(2)O, (beta-CD)(2).BiI(7).17H(2)O and (beta-CD)(2).VI(7).14H(2)O (named beta-M, M stands for the corresponding metal) are investigated in the temperature range of 30-140 degrees C. At room temperature all systems show an initial strong band at 178 cm(-1) that reveals similar intramolecular distances of the disordered I(2) units (approximately 2.72 A). During the heating process beta-Na and beta-Rb display a gradual shift of this band to the final single frequency of 166 cm(-1). In the case of beta-Sr and beta-Bi, the band at 178 cm(-1) is shifted to the final single frequencies of 170 and 172 cm(-1), respectively. These band shifts imply a disorder-order transition of the I(2) units whose I-I distance becomes elongated via a symmetric charge-transfer interaction I(2)<--I3(-)-->I(2). The different final frequencies correspond to different bond lengthening of the disordered I(2) units during their transformation into well-ordered ones. In the Raman spectra of beta-V, the initial band at 178 cm(-1) is not shifted to a single band but to a double one of frequencies 173 and 165 cm(-1), indicating a disorder-order transition of the I(2) molecules via a non-symmetric charge-transfer interaction I(2)<--I3(-)-->I(2). The above spectral data show that the ability of I3(-) to donate electron density to the attached I(2) units is determined by the relative position of the different metal ions and their ionic potential q/r. The combination of the present results with those obtained from our previous investigations reveals that cations with an ionic potential that is lower than approximately 1.50 (Cs(+), Rb(+), Na(+), K(+) and Ba(2+)) do not affect the Lewis base character of I3(-). However, when the ionic potential of the cation is greater than approximately 1.50 (Li(+), Sr(2+), Cd(2+), Bi(3+) and V(3+)), the M(n+)...I3(-) interactions become significant. In the case of a face-on position of the metal (Sr(2+), Bi(3+)) relative to I3(-), the charge-transfer interaction is symmetric. On the contrary, when the metal (Li(+), Cd(2+), V(3+)) presents a side-on position relative to I3(-), the charge-transfer interaction is non-symmetric.

Two interconverting pentaiodide forms in the cyclomaltohexaose (alpha-cyclodextrin) polyiodide inclusion complex with sodium ion: dielectric and Raman spectroscopy studies.

The polycrystalline inclusion complex of cyclomaltohexaose, (alpha-CD)(2) x NaI(5) x 8H(2)O, has been investigated via dielectric spectroscopy over a frequency range of 0-100 kHz and the temperature range of 125-450 K. Additionally, a Raman spectroscopy study was accomplished in the temperature ranges of (i) 153-298 K and (ii) 303-413 K. The ln sigma versus 1/T variation revealed the order-disorder transition of some normal hydrogen bonds to those of a flip-flop type at 200.9 K. From 278.3 up to 357.1K, the progressive transformation (H(2)O)(tightly bound)-->(H(2)O)(easily movable) takes place resulting in an Arrhenius linear increment of the ac-conductivity with activation energy E(a)=0.32 eV. In the range of 357.1-386.1K a second linear part with E(a)=0.55 eV is observed, indicating the contribution of sodium ions via the water-net. The rapid decrease of the ac-conductivity at T>386.1K is due to the removal of the water molecules from the crystal lattice, whereas the abrupt increase at T>414.9 K is caused by the sublimation of iodine. The Raman bands at 160 and 169 cm(-1) indicate the coexistence of (I(2) x I(-) x I(2)) and (I3(-) x I(2)<-->I(2) x I3(-)) units, respectively. The (I3(-) x I(2)<-->I(2) x I3(-)) units are presented as form (I), and their central I(-) ion is disordered in occupancy ratio different from 50/50 (e.g., ...60/40...70/30...). The(I(2) x I(-) x I(2)) units are displayed by the 2 equiv forms (IIa) and (IIb). In (IIa) the central I(-) ion is twofold disordered in an occupancy ratio of 50:50, whereas in (IIb) the central I(-) ion is well-ordered and equidistant from the two I(2) molecules. At low temperatures the transformation (I)-->(IIa) takes place, whereas at high temperatures the inverse one (IIa)-->(I) happens. X-ray powder diffraction and Rietveld analysis revealed a triclinic crystal form with space group P1 and lattice parameters that are in good agreement with the theoretical values.