Pulling mechanism

The process of growing a pure crystal is sensitive to a host of process parameters that impact the iacorporation of impurities ia the crystal, the quality of the crystal stmcture, and the mechanical properties of the crystal rod. For example, the crystal-pulling mechanism controls the pull rate of the crystallisa tion, which affects the iacorporation of impurities ia the crystal, and the crystal rotation, which affects the crystal stmcture. 

The HIV-1 protease, like other retroviral proteases, is a homodimeric aspartyl protease (see Fig. 1). The active site is formed at the dimer interface, with the two aspartic acids located at the base of the active site. The enzymatic mechanism is thought to be a classic acid-base catalysis involving a water molecule and what is called a push-pull mechanism. The water molecule is thought to transfer a proton to the dyad of the carboxyl groups of the aspartic acids, and then a proton from the dyad is transferred to the peptide bond that is being cleaved. In this mechanism, a tetrahedral intermediate transiently exists, which is nonconvalent and which is mimicked in most of the currently used FDA approved inhibitors. 

The mechanistic interpretation of the acid-catalyzed ring opening reaction of thiirane oxides is based on the push-pull mechanism with a transition state in which the bonded hydrogen atom plays a major role (see equation 59). 

The MM calculations show (77) that for a metal ion the size of five-coordinate high-spin Fe(II) in a porphyrin, there is a very small difference in energy between whether the Fe(II) rises up out of the plane or remains in the plane of the porphyrin. Thus, a small modification of the bell-pull mechanism (80) of hemoglobin may be that the high-spin Fe(II) with no oxygen coordinated to it does not rise out of the... 

Y Kiso, K Ukawa, T Akita. Efficient removal of /V-bcnzyloxycarbonyl group by a push-pull mechanism using thioanisole-trifluoroacetic acid, exemplified by a synthesis of Met-enkephalin. Chem Commun 101, 1980. 

This is an example of acid catalysis and the effect is to pull electrons away from the leaving group. Often both acid catalysis and nucleophilic attack are involved in enzyme-catalysed reactions in what are known as push-pull mechanisms. 

The cleavage of the 0-0 bond of the hydroperoxide is promoted by the push-pull mechanism shown in Fig. 4, in which the native HRP reacts with the unionized form of the hydroperoxide. Thus, the latter is converted into a much better nucleophile upon transfer of its proton to the distal basic group (His 42). 

Whether there are any cost-effective, flexible pull mechanisms that can supplement the patent system, is, however, an open question. Below, I examine three proposals for pull incentive mechanisms. None of them is perfect. The question is whether any of them is likely to be worth investing the billions of dollars they would likely cost, diverting money away from direct research funding and public-private partnerships. 

The nature of the bonding in Zeise s anion and other r -olefin complexes is illustrated in Fig. 18.2. Without the push-pull mechanism, the 7r electrons of the olefin would have little or no tendency to allow themselves... 

The regiochemistry observed in the EGA-catalyzed displacement of methoxyl group with nucleophiles is promising For example, the carbenium ion formed from compound 29 in methanolic solution is trapped to produce the thermodynamically stable compound 30. However, in CHjClj, a concerted push-pull mechanism ( push by nucleophile and pull by EGA) is operative leading to the exclusive formation of 31. 1-Menthone 32 can be acetalized by EGA catalysis without epimerization at C-2... 

Pull mechanisms reward innovation through enhanced profits. In general, their main advantage over push mechanisms is that firms are rewarded for success in innovating. This is an attractive property since it aligns the interests of the innovator (profits) with the interests of society (new and improved products). In addition, there is no payment made under pull mechanisms for failed innovation. 

The standard pull mechanism is the patent system, which offers the reward of exclusive use of the innovation. The patent system is designed so that innovators with products that are highly valued relative to the cost of manufacture will be able to earn large profits, since the patentee is granted exclusive use of the innovation disclosed in the patent for a period of 20 years. 

AMC thus offers a way to make development of vaccines profitable, but is a pull mechanism since the sponsor pays only if the product meets the technical requirements and sells lots of units. Thus, the incentives are made similar to those of drugs for global diseases, in which innovators receive healthy profits only if their drug is approved and is purchased at a high price by many consumers. In addition, the sponsor has to make disbursements only if vaccine development leads to a product that consumers value it bears no unwanted risks. 

In the in-line push-pull mechanisms of Rabin and Roberts, the highest energy transition state may be either the pentacovalent intermediate or the alkoxide (hydroxide) state with 02 or 05" deprotonated but not bonded to P. Incipient deprotonation of 02 in an activated state is equivalent. Protonation of X or Y or nearby positive charge could stabilize the pentacovalent intermediate. Removal of either could facilitate formation of the alkoxide in the breakdown of the intermediate. Restoration of the initial state of the enzyme is required in this mechanism and could be rate limiting. In the adjacent (pseudorotation) models of Witzel, Hammes, Usher, or Wang protonation of X or Y would be required to allow one of the two pseudomers to exist. In step 1 this requirement (and thus perhaps a rate limiting process) applies to the attack by 02. Deprotonation would force or facilitate reversal or pseudorotation to... 

Quite fascinating compounds are the super-basic nitriles102. The cyanamides are the most basic nitriles presently known103,104. The high basicity of such compounds is explained by a so-called push-pull mechanism, described schematically by the resonance structures. 

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