Oxygenase, mimics

Inhibitors for 2-OG dependent iron oxygenases thus have a huge pharmaceutical potential as future drugs. In particular inhibitors for prolyl 4-hydroxylase could help to control collagen production (34,36). Such an inhibitor should mimic the k 0, 0 chelate coordination of 2-OGs but should not react with O2. A -Oxalylglycine (Fig. 3) is such an inhibitor for prolyl 4-hydroxylase (IC50 = 3 pM) (34,36). 

Deprotonation of 1 at C3 yields an ene-diolate intermediate to which phospho-glycolohydroxamate (PGH) 9 bears a close structural resemblance (Scheme 2.2.5.3). In collaboration with J. V. Schloss, 9 was found to be a potent inhibitor not only of FucA, but indeed also of all currently accessible Class 11 aldolases with Ki in the nanomolar range [12]. Obviously, the hydroxamate mimics very effectively an advanced catalytic intermediate or transition state that is shared by these enzymes, and seems to be bound by all Zn -dependent aldolases in a very similar fashion. Interestingly, when the active-site Zn is replaced by Co ions, catalytic activity is restored and actually becomes higher than with native zinc cofactor. However, the RhuA Co complex catalyzes an oxygenase reaction that consumes... 

This chapter will describe the detailed mechanisms of 02 activation by a main representative of each class of hemoproteins. Then, efforts to mimic oxygenases by using model systems based on metalloporphyrins will be reviewed. In fact, metalloporphyrin model systems have proved to be useful for three main objectives. The first is to determine the detailed structure of the iron complexes... 

K. B. Sharpless, T. C. Flood, Oxotransition metal oxidants as mimics for the action of mixed-function oxygenases. "NIH shift" with chromyl reagents, /. Am. Chem. Soc. 93 (1971) 2316. 

Reaction mimic for the cytochrome P-450 mono-oxygenase/reductase system [Fe HMeCN)l+/O2/PhNHNHPh/substrate]... 

Table 6-4 summarizes the product yields from the combination of substrate [PhaP, Ph2S(O), PhCH2OH, or 1,4-cyclohexadiene] with O2, PhNHNHPh, and FelKMeCN) in dimethylformamide. 15 The system acts as an effective mono-oxygenase/dehydrogenase, and as such mimics the reaction cycle of the cytochrome P-450 mono-oxygenase/reductase system. 

Reaction Mimic for the Methane Mono-oxygenase Proteins Fe DPAH)2/O2lPhNHNHPh/substrate... 

RuPcY and Co and Mn-tetraphenylporphyrin Y (tePPorY) have been examined as mimics for methane oxygenase (27). Table 5 gives relevant data. Traces of methanol seem to be obtained from methane but at reaction temperatures (above 573 K) where the stability in time of the catalysts was very limited as evidenced by the large CO2 yield. Personally, we have not yet been able to reproduce these data. 

Preliminary work on the synthesis and characterisation of other zeozymes, e.g. as mimics for methane oxygenase and hydrogenases, has been reported. Also claims as to the incapsulation of porphyrins have appeared. However, it is not clear whether the materials are good enough to function as stable catalysts. Moreover, a number of specific zeolite effects have been reported but need verification and rationalization. 

CU2O2 structure 13 3 (a tran5- X-l,2-peroxo complex). In both cases association of two mononuclear copper(I) centers takes place. These functional mimics of O2 activating systems provide the key information for further design of dinuclear copper complexes with oxygenase activity. 

The CuCl/py system has been reported to mimic tryptophan-2, 3-d i oxygenase, effecting oxidative cleavage of 44 [218]. 

Oxidation. Since some metalloenzymes such as cytochrome P-450 and methane mono-oxygenase can selectively oxidize alkanes with dioxygen, there are many approaches that mimic the reactivity of these metalloenzymes using various artificial metal complexes (1,23,24). The first approach is to combine dioxygen and reducing agents in the presence of metal complexes (eq. (12)). 

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