Harris W R, Berthon G, Day J P, Exley C, Flaten T P, Forbes W F, Kiss T, Orvig C, Zatta P F
Department of Chemistry, University of Missouri-St. Louis 63121, USA.
J Toxicol Environ Health. 1996 Aug 30;48(6):543-68.
As a "hard", trivalent metal ion, Al3- binds strongly to oxygen-donor ligands such as citrate and phosphate. The aqueous coordination chemistry of Al is complicated by the tendency of many Al complexes to hydrolyze and form polynuclear species, many of which are sparingly soluble. Thus there is considerable variation among the Al stability constants reported for several important ligands. The complexity in the aqueous chemistry of Al has also affected Al toxicity studies, which have often utilized poorly characterized Al stock solutions. Serum fractionation studies show that most Al is protein bound, primarily to the serum iron transport protein transferrin. Albumin appears to play little, if any, role in serum transport. There is little agreement as to the speciation of the remaining low-molecular mass fraction of serum Al. The lability of the Al3+ion precludes the simple separation and identification of individual Al complexes. Computational methods are available for detailed computer calculations of the Al speciation in serum, but efforts in this area have been severely hampered by the uncertainties regarding the stability constants of the low molecular mass Al complexes with citrate, phosphate, and hydroxide. Specific recommendations for further research on Al speciation include: (1) Determine more accurate Al stability constants with critical low molecular mass ligands such as citrate and phosphate; (2) supplement traditional potentiometric studies on Al complexes with data from other techniques such as 27Al-NMR and accelerator mass spectrometry with 26Al; (3) develop new methods for generating reliable linear free energy relationships for Al complexation; (4) determine equilibrium and rate constants for Al binding to transferrin at 37 degrees C; (5) confirm the possible formation of low-molecular-mass Al-protein complexes following desferrioxamine therapy; (6) continue research efforts to incorporate kinetic considerations into the present equilibrium speciation calculations; (7) improve methods for preparing chemically well-defined stock solutions for toxicological studies; (8) incorporate more detailed speciation data into studies on Al toxicity and pharmacokinetics; and (9) incorporate more detailed speciation data into future epidemiological studies on the relationship between Al toxicity and various water quality parameters.
作为一种“硬”的三价金属离子，Al³⁺ 能与柠檬酸根和磷酸根等给氧体配体强烈结合。铝的水相配位化学较为复杂，因为许多铝配合物有水解并形成多核物种的倾向，其中许多物种的溶解度很低。因此，针对几种重要配体所报道的铝稳定常数存在相当大的差异。铝水相化学的复杂性也影响了铝毒性研究，这类研究常常使用特征描述不充分的铝储备溶液。血清分级分离研究表明，大部分铝与蛋白质结合，主要是与血清铁转运蛋白转铁蛋白结合。白蛋白在血清转运中似乎作用甚微，即便有作用也不大。对于血清中剩余低分子量部分铝的形态，目前尚无定论。Al³⁺ 离子的不稳定性使得难以简单地分离和鉴定单个铝配合物。计算方法可用于详细的计算机计算血清中铝的形态，但该领域的研究因低分子量铝配合物与柠檬酸根、磷酸根和氢氧根的稳定常数存在不确定性而受到严重阻碍。关于铝形态进一步研究的具体建议包括：(1) 确定铝与柠檬酸根和磷酸根等关键低分子量配体更准确的稳定常数；(2) 用²⁷Al - NMR 和含²⁶Al 的加速器质谱等其他技术的数据补充关于铝配合物的传统电位滴定研究；(3) 开发新方法以生成可靠的铝络合线性自由能关系；(4) 确定 37℃ 时铝与转铁蛋白结合的平衡常数和速率常数；(5) 确认去铁胺治疗后是否可能形成低分子量铝 - 蛋白质复合物；(6) 继续开展研究工作，将动力学因素纳入当前的平衡形态计算；(7) 改进用于毒理学研究的化学性质明确的储备溶液的制备方法；(8) 将更详细的形态数据纳入铝毒性和药代动力学研究；(9) 将更详细的形态数据纳入未来关于铝毒性与各种水质参数之间关系的流行病学研究。
