Monitoring molecular motions

To fully understand the performance of amorphous materials, it is necessary to be able to measure the molecular mobility of the samples on interest. This is because at temperatures as far as 50 K below the glass transition temperature, pharmaceutical glasses exhibit significant molecular mobility that can contribute to both chemical and physical instability.The main techniques that have been developed for monitoring molecular motions in amorphous materials are nuclear magnetic resonance (NMR) and calorimetric techniques (e.g., DSC and isothermal microcalorimetry). Average molecular relaxation times and relaxation time distribution functions obtained from these... 

A technique related to spin labeling uses spin probes to monitor molecular motion. In this technique, a radical is synthesized that mimics as closely as possible the structure of the molecule under investigation. Again nitroxyl radicals are the most suitable candidates. An example of their use is in the study of polymer melts a spin probe is introduced into the polymer and then its rate of tumbling is measured as the polymer changes its viscosity and/or undergoes phase changes. 

Solid state 2H NMR parameters are almost exclusively governed by the quadrupole interaction with the electric field gradient (EFG) tensor at the deuteron site.1 8 The EFG is entirely intramolecular in nature. Thus molecular order and mobility are monitored through the orientation of individual C-2H bond directions. Therefore, 2H NMR is a powerful technique for studying local molecular motions. It enables us to discriminate different types of motions and their correlation times over a wide frequency range. Dynamics of numerous polymers has been examined by solid state 2H NMR.1 3,7,9 Dynamic information on polypeptides by NMR is however limited,10 26 although the main-chain secondary structures of polypeptides in the solid have been extensively evaluated by 13C and 15N CP/MAS NMR.27,28... 

T as well as the spectra can reflect the nature of the molecular motions monitored at... 

The electrochemical behavior of 14+ is particularly clean and interesting, since only the 4- and the 5-coordinate geometries can be obtained on translating the metal-complexed ring from the phen site to the terpy site)841 The electrochemically induced molecular motions (square scheme1851), similar to those represented in Figure 10 but now involving stopped compounds, can be monitored by cyclic voltammetry (CV) and controlled potential electrolysis experiments)851... 

Since its first description in 1971 [35], gel-phase NMR was applied to peptide chemistry by Manatt and coworkers [36, 37], These authors used 13C NMR to determine the extent of chloromethylation of crosslinked polymers and 19F NMR to monitor protection-deprotection reactions. These two nuclei are the most commonly used in these types of studies, mainly because of their significant chemical shift dispersion, which can alleviate in part the resolution loss due to the non ideal linewidth obtained in the gel state. Apart from restricted molecular motion, that shortens T2 because of an efficient transverse relaxation, other sources of line-broadening derive from magnetic susceptibility variations within the sample (due to the physical heterogeneity of the system) and residual dipolar couplings. 

In addition to the identification of crystal moditications, SSNMR has been used to monitor reactivity and phase changes in different polymorphic forms. For instance, Harris and Thomas (1991) followed the photochemical conversion of formyl-fran -cinnamic acid with SSNMR (see also Section 6.4). Variable temperature techniques have been used to study the interconversion of four polymorphic modifications of sulphanilamide (/ -amino-benzenesulphonamide), including interpretation of at least some of the molecular motions during the course of the transformation (Frydman et al. 1990). A similar combination was augmented with colourimetric techniques to study the coexistence of two phases in the course of a phase transition (Schmidt et al. 1999). Of course, differences between unsolvated and solvated or hydrated crystal moditications may also be readily characterized by the SSNMR technique, as was done with the anhydrous and monohydrate of oxyphenbutazone (Stoltz et al. 1991). Due to the availability of the crystal structures for both modifications the SSNMR results could be interpreted directly in terms of the different atomic environments, especially for the differences in hydrogen bonding in the presence... 

Exactly the same results were obtained with spin diffusion experiments performed at ZSM-39. Frequencies can be affected by spin diffusion between sites having different NMR parameters, when, for example, magnetization is transported through a solid by means of mutual spin "flip-flops" that can occur even in the absence of atomic or molecular motion. By monitoring the correlation among frequencies in the different dimensions of a multidimensional NMR experiment, it is possible to learn about the mechanisms and rates of reorientation and diffusion processes in solids (32). 

Time-resolved fluorescence depolarization studies have, over the past decade, provided an interesting method for monitoring molecular reorientational motions in solution. The technique has been applied to investigations of both nthetic polymers and macromolecules of biological interest, and a selection of the results of these are discussed here. However, until recently, the relatively pc r quality of much of the data available from these measurements has precluded detafled quantitative interpretations of the results. With the advent of improved experimental techniques for fluorescence decay time determinations due in part to the availability of pulsed lasers for sample excitation and more accurate data analysis procedures, it is envisaged that interest in the technique may be revived. We will present here a short recapitulation of the background to these experiments, following from Sect. A. V. 

One way of studying molecular motions involves monitoring the reduction of dipole-dipole couplings probed by DQ spinning sidebands. The site selectivity is particularly high for heteronuclear DQ coherences. In Fig. 8, simulated sideband patterns are plotted for the C-H group, which is a sensitive probe of phenylene rotational motions, often met in practice. At low temperatures, one would expect... 

Shape control and the development of shape-responsive molecules relies also on the availability of analytical tools that provide spatial resolution down to subnanometer scale, strong contrast with respect to the chemical composition and physical properties, sensitivity to molecular forces in the pN range, and in-situ monitoring of molecular motion and conformation with a time resolution down to and even below milliseconds. 

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