Secondary H-Bonding

The importance of secondary interactions in modulating the chemistry of a metal-bound water or hydroxide moiety has been discussed for metaUoenzymes of varying function [42, 43). For example, in zinc-containing carbonic anhydrase II, the zinc-bound hydroxide acts as a H-bond donor to a threonine residue (Thrl99 Fig. 8.7) [37]. This interaction orients the lone pair of the hydroxide and reduces the entropic barrier for catalysis [44]. Notably, perturbation of this H-bonding interaction is reported to increase the Zn-OH2 pJCa value by around 2 units [45]. The threonine residue also stabilizes the transition state via H-bonding and destabilizes the product (bicarbonate-bound) form of the enzyme. It is also interesting that an X-ray diffraction study of crystals of carbonic anhydrase II isolated at pH 7.8 revealed two water molecules that donate H-bonds to the zinc-bound hydroxide (Fig. 8.7) [46]. 

Studies of Cu(II) and Co(III) complexes having internal H-bond donors produced similar conclusions [50, 51]. For example, comparison of the pK, values of the bound water molecules in [(2,9-diamino-o-phenanthroline)Cu(OH2)2j (1, plCa = 5.5), [(2,9-dimethyl-o-phenanthroline)Cu(OH2)2j (2, pKa=7.0) and [(ter-pyridyl)Cu(OH2)] (3, pfCa=8.2) (Fig. 8.10) revealed that the complex having internal H-bond donors (1) had the most acidic water molecule. This issue was further examined by analyzing the acidity of an analog complex having internal H-bond acceptor moieties (4, Fig. 8.10). For this Cu(II) aqua complex, a pKa of 

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When phenol, the functional group of the Tyr residue, was paired with water, the optimal geometry was found [154] to contain the expected OH- - -O H-bond. The phenol could serve as either proton donor or acceptor, but in either case, one of the C-H groups of the phenol was in position to form a secondary H-bond as illustrated in Fig. 11. No estimate was made of the energetic contribution of this secondary interaction. 

H-bonding pairs 7-6, 7-10, and 8-9, and (b) representation of the primary H-bonds (black dashed lines) and secondary H-bonding interactions (green arrows, favorable secondary interactions red arrows, unfavorable secondary interactions) for three different triply H-bonded pairs. 

In this chapter, I summarize newly discovered fundamental chemistry of synthetic complexes that provides insight into how (i) primary and secondary coordination sphere components influence the acidity and structural features of a metal-bound water molecule, and (ii) how secondary H-bonding interactions influence the metal coordination properties and hydrolytic reactivity of phosphate esters. 

Secondary H-Bonding Effects on Substrate Coordination, Activation and Cataiytic Hydroiysis invoiving Phosphate Esters... 

Fig. 8.20 Ligands used by Kramer and coworkers to examine secondary H-bonding effects on phosphate ester cleavage [115].

Fig. 8.21 (a) ORTEP representation of the cationic portion of [(L4)2Cu2(1, 3-/r-03P0Ph)2(0H2)2](N03)4 [115]. Ellipsoids are drawn at the 35% probability level, (b) Representation of one of the two copper centers of this complex showing secondary H-bonding interactions. 

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