Reaction center shielding

Through contacts between the methyl groups of Val99 and those of Leu383 the closed loop also forms a hydrophobic surface across the reaction center, shielding it from solvent (Fig. 5, see color plate). In the /3-maltose-treated enzyme this surface extends over the area between the two bound maltose molecules (or middle a-D-glucosidic linkage of... 

A more complete list of early applications of QM/MM methods to enzymatic reactions can be found elsewhere [18, 35, 83, 84], Gao [85] has reviewed QM/MM studies of a variety of solution phenomena. QM/MM methods have also been used to study the spectra of small molecules in different solvents [86] and electrochemical properties of photosynthetic reaction centers within a protein environment [87-89], An approach has also been developed for calculation of NMR shielding tensors by use of a QM/ MM method [90]. 

A considerable fraction of charge in adduct 26 seems to be delocalized into the benzenoid ring, as indicated by the shielding of the 6-position to which the charge can be effectively relayed from the reaction center (resonance formula 28). 

Similar conclusions are reached for the distribution of electron density in the isomeric adduct 101, where the carbon atoms adjacent to the reaction center are shifted upheld with respect to the corresponding 1,4-dihydropyridazine. Somewhat higher shielding is found for the C-5 atom (8.0 ppm) than for C-3 (3.7 ppm), but in either position the electron density appears to be appreciably lower than for C-4 in adduct 100. Such differences are presumably to be related to the nature of the lithium-nitrogen bond, but clearly to a hrst approximation all the adducts from diazines and phenyllithium can be described as undissociated species, whether that bond is ionized or strongly polar covalent. 

Ion radicals of conjugated acyclic or aromatic hydrocarbons (butadiene or naphthalene) are typical examples of the species with a released unpaired electron. They are named ir-elec-tron ion radicals and have a spin distribution along the whole molecular contour. An important feature of such species is that all the structural components are coplanar or almost coplanar. In this case, spin density appears to be uniformly or symmetrically distributed over the molecular framework. Spin-density distribution has a decisive effect on the thermodynamic stability of ion radicals. In general, the stability of ion radicals increases with an enhancement in delocalization and steric shielding of the reaction centers bearing the maximal spin density. 

One observation raises the question of whether enough is known about the carbonium-ion lifetime in enzymic sites to be certain that it is always as short as estimated for reactions in water. The crystal structure of soybean beta-amylase complexed either with /8-maltose or maltal shows features strongly suggesting that the reaction center is shielded from solvent.101 A mechanism involving a carbonium-ion transition state with C-l unsubstituted and subject to attack by a structurally positioned water molecule, to form a product of /3-configurat.ion, is likely for the inverting reactions... 

FIGURE 2. Photosystem II reaction center emphasizing polypeptide interactions on the lumen side of the membrane, including the shielding of the COOH-domain of the cyt 6-559 a subunit by the OEC 33 kDa protein, and the coordination and shielding of the 4 Mn of the OEC. Each D1-D2 trans-membrane unit symbolizes 2 a-helices, one for each protein. Together with 2 copies of cyt 6-559 a-p, and 1-2 other small polypeptides, the PSII reaction center core is predicted to contain 15-16 /raws-membrane Qt-helices. 

The stability of phenoxy radicals is determined by the effect of conjugation of the unpaired electron with the system of the remaining bonds and by steric effects. The introduction of such voluminous substituents as tertiary butyl and phenyl, which shield the reaction centers of the radicals, sharply increases their stability. Radicals of imsubstituted or incompletely substituted phenols readily recombine or disproportionate, and do not accumulate in significant concentrations [4]. There is no direct and distinct relationship between the stability of the radical and the effectiveness of the corresponding phenol as an inhibitor, since the effectiveness depends not only on the reactivity of the OH-bond, but also on a number of other factors. However, there is a general correspondence between the stability of the radical and the effectiveness of the corresponding phenol. 

CP-1 was assembled in an approximately spherical shape with the purest graphite in the center. About 6 tons of luanium metal fuel was used, in addition to approximately 40.5 tons of uranium oxide fuel. The lowest point of the reactor rested on the floor and the periphery was supported on a wooden structure. The whole pile was surrounded by a tent of mbberized balloon fabric so that neutron absorbing air could be evacuated. About 75 layers of 10.48-cm (4.125-in.) graphite bricks would have been required to complete the 790-cm diameter sphere. However, criticality was achieved at layer 56 without the need to evacuate the air, and assembly was discontinued at layer 57. The core then had an ellipsoidal cross section, with a polar radius of 209 cm and an equatorial radius of309 cm [20]. CP-1 was operated at low power (0.5 W) for several days. Fortuitously, it was found that the nuclear chain reaction could be controlled with cadmium strips which were inserted into the reactor to absorb neutrons and hence reduce the value of k to considerably less than 1. The pile was then disassembled and rebuilt at what is now the site of Argonne National Laboratory, U.S.A, with a concrete biological shield. Designated CP-2, the pile eventually reached a power level of 100 kW [22]. 

The importance of the o-hydroxyl moiety of the 4-benzyl-shielding group of R,R-BOX/o-HOBn-Cu(OTf)2 complex was indicated when enantioselectivities were compared between the following two reactions. Thus, the enantioselectivity observed in the reaction of O-benzylhydroxylamine with l-crotonoyl-3-phenyl-2-imi-dazolidinone catalyzed by this catalyst was 85% ee, while that observed in a similar reaction catalyzed by J ,J -BOX/Bn.Cu(OTf)2 having no hydroxyl moiety was much lower (71% ee). In these reactions, the same mode of chirality was induced (Scheme 7.46). We believe the free hydroxyl groups can weakly coordinate to the copper(II) ion to hinder the free rotation of the benzyl-shielding substituent across the C(4)-CH2 bond. This conformational lock would either make the coordination of acceptor molecules to the metallic center of catalyst easy or increase the efficiency of chiral shielding of the coordinated acceptor molecules. 

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