Phosphate, zinc interactions

M aqueous NaOH (done quickly before the subsequent hydrolysis could occur to any extent) showed the monodeprotonation with pKa value of 9.1, which was assigned to the 25a = 25b equilibrium. The pK value was higher than that of 7.3 for 24a under the same conditions, which is ascribable to the proximate phosphate anion interaction with zinc(II) (like 25c). The pendent phosphodiester in 25b underwent spontaneous hydrolysis in alkaline buffer to yield a phosphomonoester-pendent zinc(II) complex 26. Plots of the first-order rate constants vs pH (=7.5 -10.5) gave a sigmoidal curve with an inflection point at pH... 

The HSAB principle states that hard acids (Fe surface) prefer to coordinate with hard bases (oxygen, phosphates). Hard interactions are normally ionic. Iron oxides can be readily formed and the anti wear mechanism starts to interact with the polymeric zinc metaphosphate, Zn(P03)2. 

Figure 10.4 Detailed view of the binding of the second zinc finger of Zif 268 to DNA. Two side chains, Arg 46 and His 49, form sequence-specific interactions with DNA. There are also three nonspecific interactions between phosphate groups of the DNA and the side chains of Arg 42, Ser 45, and His 53.

The coordinating properties of a zinc 2,2 -bipyridyl unit with adenosine 5 -triphosphate and cytidine 5 -triphosphate were studied in aqueous solution. The binding of zinc to both phosphate and ATP nitrogen donor was observed with the potential for displacement of the ATP nitrogen donor by hydroxide.426 The interaction of zinc with the phosphate groups in a platinum(II) bound 2 -deoxyguanosine 5 -monophosphate has been studied in aqueous solution, with little difference noted in the coordinating properties of the phosphate residue or backbone relative to the free nucleobase.427... 

Various other research groups have been working since the early 1990s toward rule formation for zinc-finger proteins and their interactions with DNA. Researchers believe that there are key amino acid positions on the zinc-finger protein that interact with base or phosphate positions on DNA in similar ways for different zinc-finger-DNA systems. These positions may form... 

The anionic phosphinyl portion (POi) of the phosphate group, as it comprises the backbone of nucleic acids or zinc enzyme inhibitors (see Section IV,B), may interact with Lewis acids (i.e., metal ions and hydro-... 

An intriguing contrast can be made between carboxylates and phosphates as each interacts with metal ions. In carboxylate-metal ion interactions, zinc and other metal ions typically prefer to be in the plane of the carboxylate group (Carrell et al., 1988). However, the metal ion engaged by phosphate prefers a location that is nearly 1 A out of the plane of the phosphinyl group. Additionally, even though there are several examples of bidentate carboxylate-metal ion interactions, a symmetrically biden-tate phosphinyl-metal ion interaction is not preferred. These differ-... 

The X-ray crystal structure of the inorganic phosphate (an inhibitor) complex of alkaline phosphatase from E. coli (9) showed that the active center consists of a Zn2Mg(or Zn) assembly, where the two zinc(II) atoms are 3.94 A apart and bridged by the bidentate phosphate (which suggests a phosphomonoester substrate potentially interacting with two zinc(II), as depicted in Fig. 2), and the Mg (or the third Zn) is linked to one atom of the zinc pair by an aspartate residue at a distance... 

Although the detailed catalytic mechanisms of these phosphatases have not been elucidated, an accepted general mechanism is that the two metal ions are cooperatively working by interacting directly with the scissible phosphate and stabilizing the pentacovalent intermediate (33, 45). Moreover, one zinc(II) ion generates the attacking OH ion. 

While there have been a considerable number of structural models for these multinuclear zinc enzymes (49), there have only been a few functional models until now. Czamik et al. have reported phosphate hydrolysis with bis(Coni-cyclen) complexes 39 (50) and 40 (51). The flexible binuclear cobalt(III) complex 39 (1 mM) hydrolyzed bis(4-nitro-phenyl)phosphate (BNP-) (0.05 mM) at pH 7 and 25°C with a rate 3.2 times faster than the parent Coni-cyclen (2 mM). The more rigid complex 40 was designed to accommodate inorganic phosphate in the in-temuclear pocket and to prevent formation of an intramolecular ju.-oxo dinuclear complex. The dinuclear cobalt(III) complex 40 (1 mM) indeed hydrolyzed 4-nitrophenyl phosphate (NP2-) (0.025 mM) 10 times faster than Coni-cyclen (2 mM) at pH 7 and 25°C (see Scheme 10). The final product was postulated to be 41 on the basis of 31P NMR analysis. In 40, one cobalt(III) ion probably provides a nucleophilic water molecule, while the second cobalt(III) binds the phosphoryl group in the form of a four-membered ring (see 42). The reaction of the phosphomonoester NP2- can therefore profit from the special placement of the two metal ions. As expected from the weaker interaction of BNP- with cobalt(in), 40 did not show enhanced reactivity toward BNP-. However, in the absence of more quantitative data, a detailed reaction mechanism cannot be drawn. 

Besides local toxicity, discussed above, there are numerous other modes of potential adverse interactions involving excipients (19,20). Many of these pose little threat provided the amounts of excipients are constrained to certain levels. Excessive amounts, however, can cause problems, particularly for patients who are intolerant of even modest levels. Commonly used phosphate buffers may cause calcium loss with formation of insoluble calcium phosphates when such buffers are administered in over-ambitious amounts (21). Calcium phosphate precipitation has been noted particularly in nutritional parenteral admixtures for neonates because of the high nutrient requirements. Similarly, renal toxicity has been associated with depletion of zinc and other trace metals caused by large parenteral doses of ethylenediaminete-traacetic acid (EDTA) (22). Excessive absorption of glycine solutions, when used as irrigants during transurethral resections, can cause hyponatremia, hypertension, and confusion (23). The use of preservatives has been associated with cardiac effects in a few patients (24). Premature neonates were found to be at risk for receiving toxic amounts of benzoic acid or benzyl alcohol in bacteriostatic solutions used to flush intravenous catheters (25). 

Figure 13-7 Interaction of the bound zinc ion of L-fuculose-l-phosphate aldolase and catalytic side chains with the substrate in the active site of the enzyme as revealed by X-ray crystallography and modeling. See Dreyer and Schulz.193...

Raman spectral studies of the species [MX ]("-2)- (n = 2-4 M = Zn, Cd or Hg X = Cl, Br or I) in anhydrous tributyl phosphate have been reported.1001 For the MX2 molecules, sufficient metal dihalide-solvent interaction exists to suggest bent X—M—X species with Cjv rather than D< h symmetry. The effect appears most marked for zinc(II) and least marked for mercury(II)... 

Two general methods may be employed in the preparation of hydroxylamine involving either the thermal dissociation of certain hydroxylamine compounds or the interaction of hydroxylamine hydrochloride suspended in an alcohol with the corresponding sodium alcoholate. The first of these methods was used both by Crismer,1 who distilled zinc chloride dihydroxylamate under reduced pressure and by Uhlenhut,2 who decomposed tertiary hydroxylamine phosphate. These procedures are extremely wasteful, owing to the instability of hydroxylamine at the temperatures required to bring about dissociation. Any hydroxylamine that is not isolated is totally lost. 

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