Recent studies suggest that the developmental toxicity associated with childhood lead poisoning may be attributable to interactions of Pb(II) with proteins containing thiol-rich structural zinc-binding sites. Here, we report detailed structural studies of Pb(II) in such sites, providing critical insights into the mechanism by which lead alters the activity of these proteins. X-ray absorption spectroscopy of Pb(II) bound to structural zinc-binding peptides reveals that Pb(II) binds in a three-coordinate Pb(II)-S3 mode, while Zn(II) is known to bind in a four-coordinate mode in these proteins. This Pb(II)-S3 coordination in peptides is consistent with a trigonal pyramidal Pb(II)-S3 model compound previously reported by Bridgewater and Parkin, but it differs from many other reports in the small molecule literature which have suggested Pb(II)-S4 as a preferred coordination mode for lead. Reexamination of the published structures of these "Pb(II)-S4" compounds reveals that, in almost all cases, the coordination number of Pb is actually 5, 6, or 8. The results reported herein combined with this new review of published structures suggest that lead prefers to avoid fourcoordination in sulfur-rich sites, binding instead as trigonal pyramidal Pb(II)-S3 or as Pb(II)-S5-8. In the case of structural zinc-binding protein sites, the observation that lead binds in a three-coordinate mode, and in a geometry that is fundamentally different from the natural coordination of zinc in these sites, explains why lead disrupts the structure of these peptides and thus provides the first detailed molecular understanding of the developmental toxicity of lead.

The reaction of equimolar NO with the 16 electron molecule RuHCl(CO)L(2) (L = P(i)Pr(3)) proceeds, via a radical adduct RuHCl(CO)(NO) L(2), onward to form RuCl(NO)(CO)L(2) (X-ray structure determination) and RuHCl(HNO)(CO)L(2), in a 1:1 mole ratio. The HNO ligand, bound by N and trans to hydride, is rapidly degraded by excess NO. The osmium complex behaves analogously, but the adduct has a higher formation constant, permitting determination of its IR spectrum; both MHCl(CO)(NO)L(2) radicals are characterized by EPR spectroscopy, and DFT calculations on the Ru system show it to have a "half-bent" Ru-N-O unit with the spin density mainly on nitrogen. DFT (PBE) energies rule out certain possible mechanistic steps for forming the two products. A survey of the literature leads to the hypothesis that NO should generally be considered as a (neutral) Lewis base (2-electron donor) when it binds to a 16 electron complex which is resistant to oxidation or reduction, and that the resulting N-centered radical has a M-N-O angle of approximately 140 degrees, which distinguishes it from NO(-) (bent at <140 degrees ) and from NO(+) (>170 degrees ).

The reaction of RuHCl(CO)L(2) (L = P(i)Pr(3)) with NO initially forms a 1:1 adduct, shown by DFT calculations and EPR spectroscopy (including the RuD isotopomer) to contain a bent ( 90 degree angle Ru-N-O = 143.9 degrees ) nitrosyl where the majority of the spin density is on the nitrosyl nitrogen. This radical adduct transforms further to give equimolar RuCl(NO)(CO)L(2) and RuHCl(HNO)(CO)L(2), the latter with hydride trans to the nitroxyl ligand HN=O. This is the first observation of the synthesis of coordinated HNO from NO itself. DFT calculations lead to the proposal that this H-atom transfer is effected by free NO, and the lifetime of RuHCl(HNO)(CO)L(2) is indeed qualitatively dependent on the presence of free NO.