生物无机化学3-配位化学原理

影响的因素
中心离子的电荷——同系列者电荷增大，Δ增大 中心离子的周期——同族同电荷者，周期数增大，则 Δ明显增大 重金属 配体性质——光谱化学序列 Spectrochemical Series I- < Br- < S2- < SCN- ~Cl- < F- < OH- ~ ONO- ~ HCOO- < C2O42- < H2O < NCS- < edta4- < NH3 ~ py ~ en < bpy < phen < NO2- << CN- ~ CO
Ni(NH3)6
2+
+ 3 en
K = 109.7 ΔG= -13.6 Kcal/mol
Ni(en)3
2+
+ 6 NH3
β6 =
2+ Ni(NH3)6 [Ni2+][NH3]6
= 108.6
β3 =
2+ Ni(en)3 [Ni2+][en]3
= 1018.3
例：螯合解毒剂 氨羧螯合剂
Hard Bases
O, F donor atoms very high electronegativity r ~ 120 pm typical examples are sulfate, carbonate, silicate, acetate, alcohols, ketones
软硬酸碱规则的应用举例: 200页 BAL(巯基配体)解除As、 Hg、Sb、Au中毒
脱氧血红蛋白 氧合血红蛋白
顺磁性 反磁性
高自旋 低自旋
软硬酸碱规则判断稳定性 Hard-Soft Acid-Base Concepts
Hard Lewis acids tend to combine with hard Lewis bases, and soft Lewis acids tend to combine with soft Lewis bases The important properties to consider in the classification of Lewis acids and bases are electronegativity, size and charge. 硬亲硬，软亲软，软硬交界就不管 软亲软，硬亲硬，软硬结合不稳定
Metal in centFra Baidu bibliotekr
Ligands at corners
Orbitals not pointed directly at ligands, lower in energy
Splitting of the 3d orbitals
Δo = E(eg) – E(t2g) = 10 Dq
2 E(eg) + 3 E(t2g) = 0 E(t2g) = -4Dq = -0.4 Δo E(eg) = 6Dq = 0.6 Δo
most metals electronegativity between 0.7 and 1.6 small (<90 pm) often highly charged (3+ or higher)
Soft Bases
C, P, As, S, Se, Te, Br, I donor atoms electronegativity between 2.1 and 2.96 radius > 170 pm
晶体场稳定化能
Crystal Field Stabilization Energies (CFSE) as a Function of Electron Count and Spin State
不同金属的稳定性大小比较
[Fe(H2O)6]2+ 顺磁性
[Fe(CN)6]4反磁性
血红蛋白是一种Fe2+－卟啉－蛋白质混合配体配合物, 八面体构型：
光谱化学序列解释？ 反馈π键
CN-、CO中毒
Crystal Field Stabilization Energy (CFSE)
Δo
Δo
Weak field Δo < P (pairing energy) High spin
Strong field Δo > P (pairing energy) Low spin
Stability of transition metal coordination complexes
Chelate Effect: Metal complexes of Chelate Effect: Metal complexes of polydentate ligands are in general more polydentate ligands are in general more stable than those containing an equivalent stable than those containing an equivalent number of monodentate ligands. number of monodentate ligands. Macrocyclic Effect: For a particular metal ion Macrocyclic Effect: For a particular metal ion complexes with macrocyclic ligands are more complexes with macrocyclic ligands are more stable than those with polydentate open stable than those with polydentate open ligand chains containing an equal number of ligand chains containing an equal number of equivalent donor atoms. equivalent donor atoms.
晶体场理论
Crystal Field Theory (CFT) 静 电 作 用
Octahedral complex: point charge ligands and the 3d orbitals
Orbitals pointed directly at ligands, higher in energy
第三章 生物无机化学体系中的 配位化学原理
金属离子, 尤其是过渡金属离子与生物分子的 相互作用一般都具有配位化学特征, 可用配位 化学方法进行理论和实验研究 探针 模拟
ActivBiotics 2008年3月宣布，其用于预防由于化疗或放疗导致的口腔黏膜炎（OM）药物M40403已 被FDA指定为罕见病用药，它主要通过靶向作用于预示产生OM的早期炎症通路而发挥疗效，具有极 大的开发潜力。 口腔黏膜炎是患者在接受化疗或放疗过程中最常见的副作用，也是导致患者早期治疗中断的主要原因。 近一半的癌症患者在治疗过程中会出现口腔粘膜炎，其中90%为实体肿瘤病人。尽管口腔粘膜炎药品 市场价值仅为10-20亿美元，但目前可选的治疗药极少，尚有很大的发展空间。 M40403为小分子药物，可模拟细胞成分（超氧化物歧化酶）的作用。氧化物歧化酶在炎症早期可发 挥双重药理作用：第一种是减轻炎症症状；第二种是减少程序性死亡的细胞数量。动物实验结果显 示，M40403对急性辐射导致的口腔粘膜炎有较好的疗效。该药进行了一系列的I-II期临床实验，共进 行了700项研究，实验证明它安全性和耐受性都比较好。 A nonpeptidyl mimic of superoxide dismutase, M40403, inhibits dose-limiting hypotension associated with interleukin-2 and increases its antitumor effects. Nature Medicine 9, 750-755 (2003) Synzyme: potent non-peptidic agents against superoxide-driven tissue ingury. Science 286, 304-306 (1999)
Soft Acids
heavy metal ions insoluble chlorides chemically inert fairly electronegative (1.9 - 2.54) large size (> 90 pm) low charge (+1 or +2)
Hard Acids