Iron(III) Complexes of Tridentate 3N Ligands as Functional Models for Catechol Dioxygenases: The Role of Ligand <i>N</i>-alkyl Substitution and Solvent on Reaction Rate and Product Selectivity

A series of iron(III) complexes of the type [Fe(L)Cl3], where L is the variously N-alkyl-substituted bis(pyrid-2-ylmethyl)amine ligand such as bis(pyrid-2-ylmethyl)amine (L1), N,N-bis(pyrid-2-ylmethyl)methylamine (L2), N,N-bis(pyrid-2-ylmethyl)-n-propylamine (L3), N,N-bis(pyrid-2-ylmethyl)-iso-butylamine (L4), N,N-bis(pyrid-2-ylmethyl)-iso-propylamine (L5), N,N-bis(pyrid-2-ylmethyl)cyclohexylamine (L6), and N,N-bis(pyrid-2-ylmethyl)-tert-butylamine (L7), have been isolated and characterized by elemental analysis and spectral and electrochemical methods. The crystal structures of the complexes [Fe(L2)Cl3] 2, [Fe(L3)Cl3] 3, and the complex-substrate adduct [Fe(L5)(TCC)(NO3)] 5a, where TCC2- is the tetrachlorocatecholate dianion, have been determined by single-crystal X-ray crystallography. The complexes [Fe(L2)Cl3] 2 and [Fe(L3)Cl3] 3 possess a distorted octahedral geometry, in which the linear tridentate 3N ligands are cis-facially coordinated to the iron(III) center, and three chloride ions occupy the remaining coordination sites. The replacement of the N-methyl group in 2 by N-n-propyl group as in 3 leads to the formation of the Fe−Npy bonds and also the Fe−Cl bonds located trans to them of different lengths. The catecholate adduct 5a also possesses a distorted octahedral geometry, in which the ligand is cis-facially coordinated to iron(III) center, TCC2- is asymmetrically chelated trans to the two pyridyl moieties of the ligand, and one of the oxygen atoms of the nitrate ion occupies the sixth coordination site. All of the present complexes have been interacted with simple and substituted catechols. The catecholate adducts [Fe(L)(DBC)Cl] and [Fe(L)(DBC)(Sol)]+, where H2DBC is 3,5-di-tert-butylcatechol and Sol = H2O/CH3CN, have been generated in situ, and their spectral and redox properties and dioxygenase activities have been studied in dimethylformamide and dichloromethane solutions. All of the complexes catalyze the cleavage of H2DBC using molecular oxygen to afford both intra- and extradiol cleavage products. The formation of extradiol cleavage products is facilitated by cis-facial coordination of the 3N ligands and availability of vacant coordination site on iron(III) center for dioxygen binding. It is remarkable that the nature of the N-alkyl substituent in 3N ligands controls the regioselectivity of cleavage, with the n-propyl, iso-butyl, iso-propyl, and cyclohexyl groups enhancing the yield of extradiol products (46−68%) in dichloromethane. The rate of oxygenation depends upon the solvent and the Lewis acidity of iron(III) center as modified by the sterically demanding N-alkyl groups-length and degree of substitution. The plot of log (kO2) versus energy of the low-energy DBC2--to-iron(III) LMCT band is linear, demonstrating the importance of the Lewis acidity of the iron(III) center in dictating the rate of the dioxygenase reaction.一系列通式为[Fe(L)Cl₃]的三价铁(iron(III))配合物，其中L为不同N-烷基取代的双(2-吡啶甲基)胺(bis(pyrid-2-ylmethyl)amine)配体，包括双(2-吡啶甲基)胺(L1)、N,N-双(2-吡啶甲基)甲胺(L2)、N,N-双(2-吡啶甲基)-正丙基胺(L3)、N,N-双(2-吡啶甲基)-异丁基胺(L4)、N,N-双(2-吡啶甲基)-异丙基胺(L5)、N,N-双(2-吡啶甲基)环己基胺(L6)以及N,N-双(2-吡啶甲基)-叔丁基胺(L7)，已通过元素分析、光谱及电化学方法分离并表征。配合物[Fe(L2)Cl₃] 2、[Fe(L3)Cl₃] 3，以及配合物-底物加合物[Fe(L5)(TCC)(NO₃)] 5a（其中TCC²⁻为四氯邻苯二酚二阴离子）的晶体结构经单晶X射线衍射法测定。配合物[Fe(L2)Cl₃] 2与[Fe(L3)Cl₃] 3均具有扭曲八面体几何构型，其中线性三齿3N配体以面式顺式配位模式与三价铁中心结合，三个氯离子占据剩余的配位位点。将配合物2中的N-甲基替换为配合物3中的N-正丙基，会导致Fe-N吡啶键以及与之反位的Fe-Cl键键长产生差异。该邻苯二酚加合物5a同样具有扭曲八面体几何构型，配体以面式顺式配位模式结合至三价铁中心；TCC²⁻以不对称螯合方式与配体的两个吡啶基团处于反位，而硝酸根的一个氧原子占据第六个配位位点。本研究中的所有配合物均与简单邻苯二酚及取代邻苯二酚发生相互作用。邻苯二酚加合物[Fe(L)(DBC)Cl]与[Fe(L)(DBC)(Sol)]⁺（其中H₂DBC为3,5-二叔丁基邻苯二酚(3,5-di-tert-butylcatechol)，Sol为H₂O/CH₃CN）已通过原位法生成，并在二甲基甲酰胺与二氯甲烷溶液中对其光谱及氧化还原性质与双加氧酶活性展开了研究。所有配合物均可催化分子氧氧化裂解H₂DBC，同时得到内二醇与外二醇裂解产物。3N配体的面式顺式配位模式，以及三价铁中心可供分子氧结合的空配位位点，均有助于外二醇裂解产物的生成。值得注意的是，3N配体中N-烷基取代基的性质可调控裂解反应的区域选择性：正丙基、异丁基、异丙基与环己基取代基可在二氯甲烷体系中将外二醇裂解产物的产率提升至46%~68%。氧合反应速率取决于溶剂以及由空间位阻N-烷基取代基（包括链长与取代度）调控的三价铁中心的路易斯酸性。log(kO₂)与低能DBC²⁻→三价铁的配体到金属电荷转移(LMCT, ligand-to-metal charge transfer)带能量的线性关系，证明了三价铁中心的路易斯酸性在决定双加氧酶反应速率中的关键作用。