Dissociation cooperativity

Size Isomers. In solution, hGH is a mixture of monomer, dimer, and higher molecular weight oligomers. Furthermore, there are aggregated forms of hGH found in both the pituitary and in the circulation (16,17). The dimeric forms of hGH have been the most carefully studied and there appear to be at least three distinct types of dimer a disulfide dimer connected through interchain disulfide bonds (8) a covalent or irreversible dimer that is detected on sodium dodecylsulfate- (SDS-)polyacrylamide gels (see Electroseparations, Electrophoresis) and is not a disulfide dimer (19,20) and a noncovalent dimer which is easily dissociated into monomeric hGH by treatment with agents that dismpt hydrophobic interactions in proteins (21). In addition, hGH forms a dimeric complex with ( 2). Scatchard analysis has revealed that two ions associate per hGH dimer in a cooperative... 

A similar case is the catalysis of Gomberg-Bachmann arylations by A,A-diphenyl-hydroxylamine, which was discovered by Cooper and Perkins (1969). As Scheme 8-46 shows, the covalent adduct cation 8.62 first loses a proton. This facilitates the homolytic dissociation, as a stable radical, A/,A-diphenylnitroxide (8.63), is formed. This... 

The molecules retain their essential character In all cases studied. This implies that the spontaneous dissociation observed under certain circumstances for H2O must be a cooperative phenomenon involving more than one H2O molecule. 

Such internal thermodynamic equilibria where A is a protein are found for non-metal components, including free coenzymes and substrates where B is a small molecule, or where free M is an ion of either a non-metal, e.g. Cl" or HCOj, or a metal, e.g. K+ or Mg2+, or is H+, and they are involved in, even necessary for, catalysis, pumping and cooperative controls of many metabolic paths. All such combinations reach equilibrium, as long as exchange is fast, where a fast rate can be taken as, say, 10-3 s for dissociation in cells. Note that equilibria with defined binding constants for AB or AM formation in any system reduce the number of variables and hence AB and AM concentrations are defined by those of free A, B and M, leaving two independent variables for each equilibrium. In some cases, the... 

The objective of the preceding equilibrium calculation has been to determine the state of a molecule such as an amino acid in the conditions that prevailed on the early Earth. The pH, degree of dissociation and the extent of the reaction all have a direct effect on the population of the species present. Temperature and cooperative effects have not been considered but serve to complicate the problem. Any prebiotic reaction scheme must take account of that troublesome restriction to chemistry - the second law of thermodynamics. 

Fahey (16) suggests that intermediate 3 dissociates formaldehyde he finds supportive evidence in the rhodium-based system by observation of minor yields of 1,3-dioxolane, the ethylene glycol trapped acetal of formaldehyde. For reasons to be discussed later, we believe the formation of free formaldehyde is not on the principal reaction pathway. (c) We have also rejected two aspects of the reaction mechanism proposed by Keim, Berger, and Schlupp (15a) (i) the production of formates via alcoholysis of a formyl-cobalt bond, and (ii) the production of ethylene glycol via the cooperation of two cobalt centers. Neither of these proposals accords with the observed kinetic orders and the time invariant ratios of primary products. 

The rate enhancement for cyclohexane dehydrogenation observed for submonolayer copper deposits may result from changes in the geometric (6) and the electronic (8) properties of the copper overlayer relative to bulk copper. Alternatively, the two metals may catalyze different steps of the reaction cooperatively. For example, dissociative adsorption on bulk copper is unfavorable because of an activation barrier of approximately 5 kcal/mol (33). 

Figure 11. Allosteric regulation A conformational change of the active site of an enzyme induced by reversible binding of an effector molecule (A). The model of Monod, Wyman, and Changeux (B) Cooperativity in the MWC is induced by a shift of the equilibrium between the T and R state upon binding of the receptor. Note that the sequential dissociation constants Kr and KR do not change. The T and R states of the enzyme differ in their catalytic properties for substrates. Both plots are adapted from Ref. 140. See color insert.

The rate enhancement observed for submonolayer Cu deposits may relate to an enhanced activity of the strained Cu film for this reaction due to its altered geometric and electronic properties. Alternatively, amechansim whereby the two metals cooperatively catalyze different steps of the reaction may account for the activity promotion. For example, dissociative Hj adsorption on bulk Cu is unfavorable due to an activation barrier of approximately 5 kcal/mol . In the combined Cu/Ru system, Ru may function as an atomic hydrogen source/sink via spillover to/from neighboring Cu. A kinetically controlled spillover of Hj from Ru to Cu, discuss above, is consistent with an observed optimum reaction rate at an intermediate Cu coverage. 

The literature on dissociation (or ionization) constants of these and related compounds is immense. We present in this section only a few examples to illustrate various aspects of cooperativity in these systems. 

In 1959, Eberson (1959, 1992) found that a family of derivatives of succinic acid shows a remarkably large negative cooperativity, i.e., gjj < < 1, which is difficult to explain on the basis of electrostatic theories only. We shall discuss these compounds in Subsection 4.8.6. At present, there is no satisfactory molecular interpretation of these findings. One of the more popular ideas, originally suggested by Jones and Soper (1936) and further elaborated upon by McDaniel and Brown (1953), is that an intramolecular hydrogen bond would facilitate the first dissociation of the proton, i.e., Kj becomes smaller (or Kj becomes larger). Also, the second proton will dissociate with more difficulty. The net effect would be a... 

Non-statistical successive binding of O2 and CO to the four heme centers of hemoglobin ( cooperativity ) has been thoroughly documented. It is difficult to test for a similar effect for NO since the equilibrium constants are very large ( 10 M ) and therefore difficult to measure accurately. It is found that the four successive formation rate constants for binding NO to hemoglobin are identical. In contrast, the rate constant for dissociation of the first NO from Hb(NO)4 is at least 80 times less than that for removal of NO from the singly bound entity Hb(NO). This demonstrates cooperativity for the system, and shows that it resides in the dissociation process. The thermodynamic implications of any kinetic data should therefore always be assessed. 

As an analogous example, the behavior of sulfonium salts can be mentioned. At mercury electrodes, sulfonium salts bearing trialkyl (Colichman and Love 1953) or triaryl (Matsuo 1958) fragments can be reduced, with the formation of sulfur-centered radicals. These radicals are adsorbed on the mercury surface. After this, carboradicals are eliminated. The carboradicals capture one more electron and transform into carbanions. This is the final stage of reduction. The mercury surface cooperates with both the successive one-electron steps (Scheme 2.23 Luettringhaus and Machatzke 1964). This scheme is important for the problem of hidden adsorption, but it cannot be generalized in terms of stepwise versus concerted mechanism of dissociative electron transfer. As shown, the reduction of some sulfonium salts does follow the stepwise mechanism, but others are reduced according to the concerted mechanism (Andrieux et al. 1994). 

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