Polymorphs reactivity difference

Li, W.K., Gong, X.Q., Lu, G., and Selloni, A. (2008) Different reactivities of Ti02 polymorphs comparative DFT calculations of water and formic acid adsorption at anatase and brookite Ti02 surfaces. Journal of Physical Chemistry C, 112 (17), 6594-6596. 

The significance of polymorphism in the pharmaceutical industry lies in the fact that polymorphs can exhibit differential solubility, dissolution rate, chemical reactivity, melting point, chemical stability or bioavailability, among others. Such differences can have considerable impact on a drag s effectiveness. Usually, only one polymorph is stable at a given temperature, the others being metastable and evolving to the stable phase... 

Crystalline packing is an important parameter for auto-oxidation in the sohd state, as molecular oxygen must be able to access susceptible moieties in the molecule. Lyn et al. [63] showed that only one (hexagonal form) of the five different polymorphic forms of prednisolone tert-butylacetate were susceptible to oxidation, yielding the 11-ketone product. The authors attributed this oxidative reactivity to channels in the crystal structure allowing access to the labile 11-alcohol position. Bryn et al. [64] also identified a similar phenomenon in the photo-mediated oxidation of 21-cortisol tert-butylacetate to the corresponding ketone. 

Detailed inspection of the crystal structure of 84 revealed that there is a certain space between reacting molecules in the crystal to allow initiation of photodimerization. The space, designated as a buffer zone , buffers the steric hindrance from which the reacting molecules suffer when they approach each other. The buffer zone is formed by the disordered piperidine rings in 84, but there is no extra space in the crystal structure of 83, and therefore photodimerization does not occur. Further evidence of this buffer zone was later reported by the same group, whereby polymorphic crystal forms had different reactivities toward photodimerization <1998BCJ321>. 

HMX is a white crystalline substance and exists in four polymorphic modifications, the P form being most stable and least sensitive. The a and forms exist at room temperature but all forms transform to 8 polymorph above 160 °C. Octogen is usually obtained in the p form which is less sensitive to impact and has a density of 1.91 gem-3 and m.p. of 291 °C. HMX and RDX are almost alike in chemical reactivity. It is non-hygroscopic, insoluble in water and soluble in organic solvents similar to RDX. They differ only in that ... 

Even more important point to note is that often times one cannot even extend the chemistry of the same molecule in the same medium under different conditions. The best examples are found in the crystalline state where molecules tend to crystallize as different polymorphs. It has been very well established that the different polymorphic forms of a compound show significant differences in photochemical behavior. A classic example that shows polymorphic form dependent reactivity is cinnamic acid. Substituted cinnamic acids crystallize in three polymorphic forms namely a, (3, and y and provide photodimers characteristic of the crystal packing (Sch. 1). One of the interesting crystal structure dependent cyclizations is that of tetrabenzoyl-ethylene [143]. Photolysis of only one of the two dimorphic modifications gives rise to a product while the other is inert to UY radiation (Sch. 25). 

Even though molecular crystal polymorphs contain exactly the same molecules or ions, they usually possess different chemical and physical properties such as density, diffraction pattern, solid-state spectra, melting point, stability and reactivity. 

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... 

Two classic studies on polymorphic systems are worthy of note here. One is the difference in the reactivity of the and y-polymorphic forms of meta substimted cinnamic acids 6-XL, in which the instantaneous rates and product distributions varied with time (Hadjoudis et al. 1972). A second example involves the compound 6-XLin (Voght et al. 1963) that has been shown to exist in a number of different crystalline modifications. A chloroform solvate (Schaeffer and Marsh 1969) is reactive towards oxygen, while Bruckner et a/. (1971) have reported the structure of an inactive form. The ability to probe the details of the reactions at the gas-solid interface with atomic force microscopy (Kaupp et al. 1996) and in the bulk by NMR imaging (Butler et al. 1992) has led to increased understanding and renewed interest in these systems that have considerable industrial promise especially due to the avoidance of solvents that otherwise would require disposal or recycling (Dittmer 1997). 

Polyclonal antibodies are widely used in clinical laboratories for the measurement of plasma protein concentrations. However, immunoassays are often sensitive to the nature of the antibody used. The development of polyclonal antibodies is affected by several factors, such as the purity and dose of the antigen used, the species of host animal, and the immunization procedure. Monoclonal antibodies are viewed as a viable alternative to alleviate these problems. However, the expression of particular epitopes varies with the hpoprotein particles and among individuals in addition, the apohpoproteins themselves are polymorphic in nature. Therefore the use of a single monoclonal antibody might not detect a particular variant. If a monoclonal antibody is used in the determination of an apohpoprotein, it should he directed to an epitope that is expressed on all polymorphic forms of that particular apoprotein. Furthermore, the epitope should be equally reactive to the antibodies regardless of which hpoprotein class contains it. Alternatively a mixture of monoclonal antibodies directed at different epitopes of the apohpoprotein may also be used. Such mixtures are referred to as panmonoclonal antibodies. 

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