Farkas Etelka, Buglyó Péter
Met Ions Life Sci. 2017 Apr 10;17. doi: 10.1515/9783110434330-008.
Lead(II) forms (NH2,COO-)-chelated mono- and bis-complexes with simple amino acids, while mono-complexes with pH-dependent coordination modes exist with simple dipeptides. These mostly hemidirected complexes have moderate stability. While a weak interaction of side chain imidazole and carboxylate in lead(II)-aminoacidato complexes is found, the thiolate group has an exceptionally high affinity to this metal ion. For example, tridentate (NH2,COO-,S-)-coordination of penicillamine (Pen) and cysteine (Cys) results in an extremely strong interaction with lead(II), but, owing to the sterical effect of the 6s2 pair, a second ligand is not able to coordinate in the above mentioned tridentate way. Although there is no example for a lead(II)-induced deprotonation and coordination of a peptide-amide and the side-chain thiolate in oligopeptides has a somewhat lower basicity compared to that of Pen or Cys, still the Cys-containing peptides interact rather strongly with lead(II). Interestingly, the position of Cys in the peptide influences significantly both the lead-binding ability via different bonding modes and the selectivity for lead(II) against other metal ions, like zinc(II) or cadmium(II). At high ligand excess, however, coordination of three sulfur donors to lead(II) is found with thiolate-containing amino acids and oligopeptides. High basicity oxygens of hydroxamates, hydroxypyronates, and hydroxypyridinonates are also effective lead-binding donors. Some factors affecting the complexation of these ligands with lead(II) are: (i) A larger extent of delocalization along the ring in hydroxypyridinonate results in a more favored metal-binding ability over hydroxypyronate. (ii) Even monohydroxamates are good ligands and form mono- and bis-complexes with lead(II). (iii) In general, dihydroxamates and trihydroxamate-based siderophores, like desferrioxamine B (DFB) and desferricoprogen (DFC), are better binding agents for Pb(II) than the monohydroxamates, but the length and structure of linkers connecting the hydroxamate moieties have a significant impact on the complexation and selectivity for lead(II). (iv) The corresponding thio derivatives are significantly better ligands for lead than their parent oxo molecules, but polymeric complexes with poor water solubility are formed in most cases. (v) Out of the hydroxamate derivatives of amino acids the α-ones are the most effective ligands, provided polynuclear species involving the hydroxamate-oxygens, amino-N and hydroxamate-N can be formed.
铅（II）与简单氨基酸形成（NH₂，COO⁻）螯合的单络合物和双络合物，而与简单二肽存在具有pH依赖性配位模式的单络合物。这些大多为半定向的络合物具有中等稳定性。虽然在铅（II）-氨基酸络合物中发现侧链咪唑和羧酸盐之间存在弱相互作用，但硫醇盐基团对该金属离子具有异常高的亲和力。例如，青霉胺（Pen）和半胱氨酸（Cys）的三齿（NH₂，COO⁻，S⁻）配位导致与铅（II）的极强相互作用，但是，由于6s²电子对的空间效应，第二个配体无法以上述三齿方式配位。尽管没有铅（II）诱导肽酰胺去质子化并配位的例子，并且寡肽中的侧链硫醇盐的碱性比Pen或Cys的碱性略低，但含Cys的肽与铅（II）的相互作用仍然相当强烈。有趣的是，Cys在肽中的位置通过不同的键合模式对铅结合能力以及对铅（II）相对于其他金属离子（如锌（II）或镉（II））的选择性都有显著影响。然而，在高配体过量的情况下，发现含硫醇盐的氨基酸和寡肽与铅（II）形成三个硫供体的配位。异羟肟酸酯、羟基吡喃酮和羟基吡啶酮的高碱性氧也是有效的铅结合供体。影响这些配体与铅（II）络合的一些因素如下：（i）羟基吡啶酮中沿环的离域程度更大，导致其金属结合能力比羟基吡喃酮更有利。（ii）即使是单异羟肟酸酯也是良好的配体，能与铅（II）形成单络合物和双络合物。（iii）一般来说，二异羟肟酸酯和基于三异羟肟酸酯的铁载体，如去铁胺B（DFB）和去铁铁载体（DFC），对Pb（II）的结合能力比单异羟肟酸酯更好，但连接异羟肟酸酯部分的连接子的长度和结构对铅（II）的络合和选择性有显著影响。（iv）相应的硫代衍生物作为铅的配体明显优于其母体含氧分子，但在大多数情况下会形成水溶性差的聚合物络合物。（v）在氨基酸的异羟肟酸酯衍生物中，α-衍生物是最有效的配体，前提是可以形成涉及异羟肟酸酯-氧、氨基-N和异羟肟酸酯-N的多核物种。
