Structural modification, hydrolytic

Phosphonate analogs to phosphate esters, in which the P—0 bond is formally replaced by a P—C bond, have attracted attention due to their stability toward the hydrolytic action of phosphatases, which renders them potential inhibitors or regulators of metabolic processes. Two alternative pathways, in fact, may achieve introduction of the phosphonate moiety by enzyme catalysis. The first employs the bioisosteric methylene phosphonate analog (39), which yields products related to sugar 1-phosphates such as (71)/(72) (Figure 10.28) [102,107]. This strategy is rather effective because of the inherent stability of (39) as a replacement for (25), but depends on the individual tolerance of the aldolase for structural modification close... 

A systematic modification of the structure was performed to make the substituent R bulkier and bulkier to protect against the possible hydrolytic detoxication mechanism. In the course of the structural modification, the QSAR analyses were utilized to get informations for structural factors to optimize the activity. The analysis for a set of 41 derivatives where R varies from simple alkyls to such congested groups as i-Pr(Me)2C and t-Bu(Cl)CH gave Eq. 34 31>,... 

Pore diameter, specific pore volume. A controlled, macroporous silica can be obtained by hydrolytic polycondensation of polyethoxysiloxane, while silica gel structure modification results from thermal or rather hydrothermal treatment. When hydrothermal treatment is carried out with silica of a pore size of 100 A at 250 C and 50 atm for a period of 15-20 h, formation of silica gel with a homogeneous pore size of 900 A is possible. Of coarse, the increase of pore diameter reduced the surface area thereby the Rf. values are also generally increased in the case of adsorption type chromatography. El Rassi et al. 44] studied the effect of water and that of hydrothermal treatment on the activity of silica gel. 

In order to prepare hydrolytically stable polythionyiphosphazenes the perchlo-rinated polymers were reacted with nucleophiles to substitute the hydrolytically sensitive main group-element halogen bonds [2]. This type of post-polymerization structural modification is well-established in polyphosphazene chemistry [2,8]. Thus, aryloxide nucleophiles or primary amines were used to substitute the polymers leading to poly(aryloxythionylphosphazenes) 24 and poly(amino-thionylphosphazenes) 25 respectively [35,37] ... 

Hydrolytic and non-hydrolytic sol-gel routes are implemented to prepare various pure and silica-dispersed vanadium- or niobium-based oxide catalysts corresponding to the compositions Nb-V, Sb-V and Nb-V-M (M = Sb, Mo, Si). Starting reagents in the hydrolytic procedure are isopropanol solutions of the metal alkoxides. The non-hydrolytic route is based on reactions between metal and Si alkoxides and hexane suspensions of niobium(V) chloride. The catalysts are tested in propane oxidative dehydrogenation. NbVOs, SbV04 and Nb2Mo30n are the major crystalline phases detected in the fresh catalysts, but structural modifications are in some cases observed after the use in the catalytic tests. At 500 C, propane conversions of 30 % and selectivities to propene between 20 and 40 % are attained. When the space velocity is decreased, acrolein is in some cases found as by-product. 

Soft -blockers. Because in this class inactive metabolite-based soft drugs can be obtained by introducing the hydrolytically sensitive functionality at a flexible pharmacophore region, there is considerable freedom for structural modifications. Consequently, transport and metabolism properties can be controlled more easily. 

The tripeptides in Fig. 6.17 underwent a few breakdown reactions (N-ter-minus elimination, Qm formation, peptide bond hydrolysis), some of which will be considered later in this section. Of relevance here was that, of the two amidated tripeptides, the amide at the C-terminus underwent deamidation predominantly (Fig. 6.17, Reaction a), which, perhaps, explains the somewhat lesser stability compared to the free carboxylic acid forms. While the hexapeptide (6.52, Fig. 6.17) followed a different pattern of decomposition [76b], deamidation was also a predominant hydrolytic reaction at all pH values. Thus, the procedure to extrapolate results from small model peptides to larger medicinal peptides appears to be an uncertain one, since small modifications in structure can cause large differences in reactivity. 

By far, 2-fluoro-2-deoxyfuranoses have been the most studied compounds. Indeed, at a structural level they are the closest analogues of 2-deoxynucleosides. Due to its electronic effect, the fluorine atom in the 2 position inhibits development of a positive charge on the anomeric carbon (which is responsible for the hydrolytic cleavage of nucleosides). In order to enhance the stability of 2-deoxynucleosides in acidic medium, and thus make oral administration of an antiviral compound easier, introduction of a fluorine atom in the 2 position is a commonly used strategy. The resulting protective effect toward proteolysis has been well demonstrated, as exemplified by the fluorinated analogues of ddl and ddA (cf. Chapter 3, Figure 3.13). However, the presence of this fluorine atoms often induces modifications in the antiviral properties of the molecule. ... 

Some results of the modification of lignin sulfonate Ultra B002 by reaction with terephthaloyl chloride are summarized in Table VI. The total hydroxyl content of the lignosulfonates as well as their derivatives are presented in Table VII. The hydrolytic resistance of selected products is evaluated in Table VIII. The results presented in Tables VI-VIII stress several advantages of the derivatives with terephthaloyl chloride. The modified lignin sulfonates were insoluble, or only very slightly soluble, in organic solvents. They were, however, soluble in dimethyl sulfoxide. Ordered structures were identified by X-ray studies (16,17). 

An obvious difficulty arises with this rather elaborate rationale when phosphoramidate and aryl phosphoramidate monoanions are compared for example, the dissimilarity of the dioxan effect yet the identity of product distribution observed in methanol-water competition experiments. Preliminary studies in the author s laboratory have revealed striking differences in the hydrolytic behavior between a series of phosphoramidafes derived from primary aliphatic amines and the above aryl systems. No linear structure-reactivity relationship between the logarithmic rate of hydrolysis of the monoanion species and the pKa of the amine is observed19. Moreover, the rate of hydrolysis of phosphoramidate monoanions derived from aliphatic amines is at least 104 times slower than those formed from aryl amines. In contrast, only a thirtyfold decrease in rate is observed for the corresponding ApKa in the O-phos-phate monoester series. The suspicion that mechanism (1), even with the above proposed modification, is not an accurate description of phosphoramidate monoanion hydrolysis derives some further support from the observation that the monoanion is subject to nucleophilic attack by substituted pyridines al-... 

In addition to structure control, metal ions can act as reactive centers of proteins or enzymes. The metals can not only bind reaction partners, their special reactivity can induce chemical reaction of the substrate. Very often different redox states of the metal ions play a crucial role in the specific chemistry of the metal. Non-redox-active enzymes, e.g. some hydrolytic enzymes, often react as a result of their Lewis-acid activity [2], Binding of substrates is, however, important not only for their chemical modification but also for their transport. Oxygen transport by hemoglobin is an important example of this [3]. 

Structure II polymers are relatively elastic when polymethylphenylsiloxanes are obtained by the hydrolytic cocondensation only of trifunctional monomers (e.g., methyl- and phenyltrichlorosilanes), there are polymers with low elasticity. Polydimethyl- and polymethylphenylsiloxanes can be modified with organic polymers (polyester, epoxy) or silicone substances, e.g. methyl(phenylaminomethyl)diethoxysilane. The modification of polydimethyl- and polymethylphenylsiloxanes improves some properties of these polymers and varnishes based on them in particular, it considerably increases adhesion and mechanical durability of varnish films. 

The simple coordination chemistry characteristic of the majority of protein-metal interactions is replaced in certain cases by irreversible covalent modifications of the protein mediated by the metal ion. These modifications are essential for the function and are templated by the structure of the protein, as no other proteins are required for the reaction to occur. These self-processing reactions result in the biogenesis of redox cofactors in some enzymes (amine oxidases, galactose oxidase, cytochrome c oxidase) and activation of hydrolytic sites in others (nitrile hydratase). The active sites of all of these enzymes are bifunctional, directing not only the catalytic turnover reaction of the mature enzyme but the modification steps required for maturation. 

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