Transition desolvation

Heats of adsorption Heats of reaction Heats of polymerization Heats of sublimation Heats of transition Desolvation reactions Desolvation reactions Solid-gas reactions Curie point determinations Purity determinations Thermal stability Oxidation stability Class transition determinations Comparison... 

X-ray powder diflraction (XRPD) provides considerably less structural information than single crystal X-ray diflraction however, it is generally considered to be the gold standard through which salt and co-crystal forms may be identified and polymorphism and solvate formation confirmed in polycrystalline soHds. Modem powder diffractometers, when equipped with temperature and/or humidity control accessories, greatly expand the range of applications of powder diffraction to include studies of solid state phase transitions, desolvation (dehydration), rehydration, melting and recrystallization. ... 

Melting point heat of fusion heat of transition desolvation temperature... 

Destabilization of the ES complex can involve structural strain, desolvation, or electrostatic effects. Destabilization by strain or distortion is usually just a consequence of the fact (noted previously) that the enzyme is designed to bind the transition state more strongly than the substrate. When the substrate binds, the imperfect nature of the fit results in distortion or strain in the substrate, the enzyme, or both. This means that the amino acid residues that make up the active site are oriented to coordinate the transition-state structure precisely, but will interact with the substrate or product less effectively. 

The possibility of an entropy-enthalpy relationship for the reaction was examined and found to give a correlation coefficient of only 0.727 which was however improved to 0.971 if only the external contributions to these parameters were used, i.e. these contributions arising from solvent interactions only. If compounds with substituents ortho to the amino group were excluded, this further improved to 0.996 and is likely therefore to be real [cf. the comments on p. 9). It was argued that the different amounts of desolvation of the aromatic on going to the transition state would depend upon the substituent, and that the resultant greater freedom for solvent molecules would mean decreased interaction energy or increased enthalpy so that the linear relationship follows. 

Using this relationship for different enzymatic reactions (e.g., Ref. 13) indicates that enzymes do not use the desolvation mechanism and that their reactions have no similarity to the corresponding gas-phase reaction, but rather to the reference reaction in water. In fact, enzymes have evolved as better solvents than water, by providing an improved solvation to the transition state (see Section 9.4). 

The second group of studies tries to explain the solvent effects on enantioselectivity by means of the contribution of substrate solvation to the energetics of the reaction [38], For instance, a theoretical model based on the thermodynamics of substrate solvation was developed [39]. However, this model, based on the determination of the desolvated portion of the substrate transition state by molecular modeling and on the calculation of the activity coefficient by UNIFAC, gave contradictory results. In fact, it was successful in predicting solvent effects on the enantio- and prochiral selectivity of y-chymotrypsin with racemic 3-hydroxy-2-phenylpropionate and 2-substituted 1,3-propanediols [39], whereas it failed in the case of subtilisin and racemic sec-phenetyl alcohol and traws-sobrerol [40]. That substrate solvation by the solvent can contribute to enzyme enantioselectivity was also claimed in the case of subtilisin-catalyzed resolution of secondary alcohols [41]. 

Phase transitions, whether first-order or second-order, are potent sources of instability of solid drugs and can usually be detected and studied by thermal methods of analysis (e.g., DSC, TGA, TMA, ODSC, DMA, DEA). In crystalline solids, typical first-order transitions are polymorphic or desolvation transitions. In amorphous solids, second-order transitions, such as glass transitions, are common. 

The formation of niclosamide hydrates, and the effect of relative humidity on the solvatomorphs obtained from acetone and ethyl acetate has been studied [79], The acetone and ethyl acetate solvatomorphs could be desolvated, and exposure to elevated humidity resulted in the formation of two hydrate structures. Each hydrate could be dehydrated into a different anhydrate phase, but only the hydrate formed from the acetone desolvate could be rehydrated to form a hydrate phase. Dynamic vapor sorption has been used to develop a method for determining the onset relative humidity of a glass transition and associated crystallization process [80]. 

The sample temperature is increased in a linear fashion, while the property in question is evaluated on a continuous basis. These methods are used to characterize compound purity, polymorphism, solvation, degradation, and excipient compatibility [41], Thermal analysis methods are normally used to monitor endothermic processes (melting, boiling, sublimation, vaporization, desolvation, solid-solid phase transitions, and chemical degradation) as well as exothermic processes (crystallization and oxidative decomposition). Thermal methods can be extremely useful in preformulation studies, since the carefully planned studies can be used to indicate the existence of possible drug-excipient interactions in a prototype formulation [7]. 

Measurements of thermal analysis are conducted for the purpose of evaluating the physical and chemical changes that may take place in a heated sample. This requires that the operator interpret the observed events in a thermogram in terms of plausible reaction processes. The reactions normally monitored can be endothermic (melting, boiling, sublimation, vaporization, desolvation, solid-solid phase transitions, chemical degradation, etc.) or exothermic (crystallization, oxidative decomposition, etc.) in nature. 

One reason for lower sensitivity is the lack of flexibility to optimize the positions of the sprayers on the MUX interface another may be the lower electrospray desolvation efficiency on the MUX. The longer total cycle time on a MUX interface with a quadrupole MS in comparison to a single sprayer interface adds another concern. Assuming typical chromatographic peak widths appeared on average at 15 sec, 17 data points could be easily detected across the peak for each transition with a total cycle time of 0.88 sec on a conventional single sprayer set-up. With the MUX, only 12 data points could be detected across the same peak even with a total cycle time of 1.24 sec because of the introduction of additional interspray time on top of dwell time. Hence, when MUX is used with a quadrupole mass analyzer, it is important to consider dwell time and chromatographic peak width... 

TG is a powerful adjunct to DSC studies, and are routinely obtained during evaluations of the thermal behavior of a drug substance or excipient component of a formulation. Since TG analysis is restricted to studies involving either a gain or a loss in sample mass (such as desolvation decomposition reactions), it can be used to clearly distinguish thermal events not involving loss of mass (such as phase transitions). 

Advances in TIMS-techniques and the introduction of multiple collector-ICP-MS (MC-ICP-MS) techniques have enabled the research on natural variations of a wide range of transition and heavy metal systems for the first time, which so far could not have been measured with the necessary precision. The advent of MC-ICP-MS has improved the precision on isotope measurements to about 40 ppm on elements such as Zn, Cu, Fe, Cr, Mo, and Tl. The technique combines the strength of the ICP technique (high ionization efficiency for nearly all elements) with the high precision of thermal ion source mass spectrometry equipped with an array of Faraday collectors. The uptake of elements from solution and ionization in a plasma allows correction for instrument-dependent mass fractionations by addition of external spikes or the comparison of standards with samples under identical operating conditions. All MC-ICP-MS instruments need Ar as the plasma support gas, in a similar manner to that commonly used in conventional ICP-MS. Mass interferences are thus an inherent feature of this technique, which may be circumvented by using desolvating nebulisers. 

A potential factor for enhancing the effectiveness of catalyzed reactions. The relative importance of this factor will depend on the polarity of the substrate (s), transition state, and reaction product(s). The energy associated with desolvation of substrates must be compensated for by the binding interactions between the substrates and the enzyme. 

The goal of this research is to develop a new class of bioresponsive materials that undergo rapid, large-magnitude, volume-phase transitions in response to specific biological stimuli. Our approach to these materials is based on two fundamental aspects of hydrogels (1) hydrogel solvation/desolvation thermodynamics can be perturbed... and... 

Our failed — at least insofar as precise transition state characterization is concerned — attempt was nonetheless instructive i) contrary to what found in ref 30, the surface version of reaction (1) does show a barrier, although small, thus Supporting the view that both desolvation of the Cl ion and weak hydrogen bonding to the nitrate group contribute to the barrier ii) reaction (1) appears to be faster than (1), if it is verified that the proton has transferred away from the adsorption site. Concerning the latter point, as noted in Sec.II., there is experimental support for the view that such a transport does not occur. On the other hand, there is other experimental support for the view that it does, so that it seems fair to say that the situation remains ambiguous from an experimental viewpoint. 

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