Activity/reactivity, 52 mechanical

While an active enzymatic mechanism produces acetoacetate from acetoacetyl-CoA in the liver, acetoacetate once formed cannot be reactivated directly except in the cytosol, where it is used in a much less active pathway as a precursor in cholesterol synthesis. This accounts for the net production of ketone bodies by the liver. 

Scheme 6 Loss of stereoinformation during the Bi(OTf)3-catalyzed Friedel-Crafts-alkylation implies a carbocationic intermediate. Mechanism A TfOH generated in situ from Bi(OTf)3 is thought to be the catalytic active species. Mechanism B Bismuth(III) acts as a Lewis acid. TfOH only regenerates Bi(OTf)3 from its less reactive monohydroxide...

For copolymerizations proceeding by the activated monomer mechanism (e.g., cyclic ethers, lactams, /V-carboxy-a-amino acid anhydrides), the actual monomers are the activated monomers. The concentrations of the two activated monomers (e.g., the lactam anions in anionic lactam copolymerization) may be different from the comonomer feed. Calculations of monomer reactivity ratios using the feed composition will then be incorrect. 

Some ROPs proceed with the simultaneous operation of two different mechanisms, for example, NCA copolymerizations initiated by some secondary amines proceed with both the amine and activated monomer mechanisms. The monomer reactivity ratios for any comonomer pair are unlikely to be the same for the two different propagations. Any experimentally determined r values are each composites of two different r values. 

The nitro group of metronidazole is chemically reduced in anaerobic bacteria and sensitive protozoans. Reactive reduction products appear to be responsible for antimicrobial activity. The mechanism of tinidazole is assumed to be the same. 

Leung, D.H., Bergman, R.G. and Raymond, K.N. (2006) Scope and mechanism of the C—H bond activation reactivity within a supramolecular host by an iridium guest A stepwise ion pair guest dissociation mechanism. J. Am. Chem. Soc., 128 (30), 9781-9797. 

The high affinity of many platinum compounds for sulfur and the availability of many sulfur-containing biomolecules have raised the question whether Pt-sulfur biomolecule interactions could serve as a drug reservoir for platination at DNA, necessary for the antitumor activity of cis-Pt. Two reaction paths are possible, i.e., spontaneous release of plantinum from the sulfur, or nucleophilic displacement of platinum from sulfur by guanine (N7), for example. At the moment, there is no real evidence for the existence of such reactivation mechanisms. In fact, it has been reported that Pt-protein interactions in the plasma (albumin) are not reversible under normal conditions (161, 165). Further, a mixture of cis-Pt-methionine products does not show antitumor properties (166), indicating no induced platination of DNA. More research is required to investigate the existence of a reactivation mechanism. However, it is predicted that if such a reactivation phenomenon is operational, the most likely candidate is the labile Pt-methionine bond, as has been shown by its rapid reaction with Naddtc, STS, and thiourea (vide supra) (131). 

Reactive pathway may follow the stimulation of angiotensin II receptors, which activate the NADPH oxidase (5). Hypertension may generate OS via this mechanism. Afurther reactive mechanism is related to the oxidized low-density lipoproteins (LDL) or even to the activity of free cholesterol on macrophages (6). 

The reactions of iron-containing enzymes with O2 often involve high oxidation states of the metal. Generally, the initial reaction of dioxygen with both heme and mononuclear non-heme ferrous enzymes results in the formation of Fe -superoxide intermediates. Highly reactive Fe =0 intermediates often are employed often for C-H activation. The mechanism of substrate oxidation by binuclear non-heme enzymes involves high valent, oxo-bridged species, with Fe in the -i-3 or +4 oxidation state. 

For the anion-catalyzed heterolysis reaction with the complex (H20)5Cr(CMc20H), the catalytic effect increases with basicity of the anion. The activation volumes are all positive, in support of a dissocia-tively activated heterolysis mechanism. Overall, the decomposition mechanism involves parallel pathways whereby hydrolytic cleavage occurs at both (H20)sCr(CMe20H) + and the more-reactive substituted complex (H20)4XCr(CMe20H)+ (Scheme 2). 

Thiamine is absorbed in the intestine by both active transport mechanisms and passive diffusion. The active form of the cofactor, thiamine pyrophosphate (thiamine diphosphate, TPP), is synthesized by an enzymatic transfer of a pyrophosphate group from ATP to thiamine (Figure 15-1). The resulting TPP has a reactive carbon on the thiazole ring that is easily ionized to form a carbanion, which can undergo nucleophilic addition reactions. 

For chemicals with the same MOA, similar structural features can be searched for assuming that they give rise to similar reactivity mechanisms. Then, the basic QSAR strategy provides for identifying critical structural elements responsible for activity via a hypothetical shared mode of action and then constructing QSAR models able to classify different modes of action. 

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