Robert D. Hancock

Metal complexes in aqueous solutions

Introductory Overview. Factors Governing the Formation of Complexes with Unidentate Ligands in Aqueous Solution: Some General Considerations. Chelating Ligands. Complexes of Macrocycles and Other More Highly Preorganized Ligands. Medical Applications of Metal Complexes. The Selectivity of Ligands of Biological Interest for Metal Ions in Aqueous Solution: Some Implications for Biology. Stability Constants and Their Measurements. Index.

The stereochemical activity or non-activity of the inert pair of electrons on lead(II) in relation to its complex stability and structural properties: some considerations in ligand design

Abstract The role of the lone pair of electrons on Pb(II) in its coordination geometry and complex stability is examined. In a series of macrocyclic ligands where oxygen donors are successively replaced by nitrogen donors, it is found that when three or four nitrogens are present, there is a sudden marked increase in the rate of change of complex stability per nitrogen donor added. This is attributed to a change from a stereochemically inactive lone pair with approximately two or fewer nitrogen donors present, to an active lone pair. Below the transition point, the Pb(II) ion behaves as a large metal ion with rather ionic ML bonding. In this state it responds to added oxygen donor bearing groups as expected for such a metal ion. Thus, the size-related selectivity patterns of Pb(II) with the ligand DAK-22 (4,7,13,16-tetraoxa-1,10-diazacyclooctadecane-N,N′-diacetate) are as expected for its size. The protonation constants and formation constants of DAK-22 with several metal ions are reported. For the complexes formed by 12-aneN4 (1,4,7,10-tetraazacyclododecane) and 12-aneN3O (1-oxa-4,7,10-triazacyclododecane) the Pb(II) appears to have a stereochemically active lone pair. Thus, when N-(2-hydroxypropyl) groups are added to 12-aneN4 and 12-aneN3O to give the ligands THP-12-aneN4 and THP-12-aneN3O, the Pb(II) ion does not respond to the added hydroxyalkyl groups as might have been expected. It behaves as a smaller more covalent ion, and a study of the formation constants of THP-12-aneN4 and THP-12-aneN3 with Cu(II), Zn(II), Cd(II), Pb(II), Ca(II), Sr(II) and Ba(II) reveals lower than anticipated Pb/Zn selectivities. A crystallographic study of [Pb(C20Hn44N4O4)](NO3)2·C3H8O reveals that there is space between the O donors for a stereochemically active lone pair, but the lack of shortening of the PbN bonds suggests that the lone pair is not active. The complex crystallizes in the orthorhombic system, space group Pnma, with cell dimensions a=10.352(8), b=14.781(2), and c=21.850(4) A, Z=4. A final conventional R=0.056 was obtained. Although the ligand THP-12-aneN4 has four chiral carbon atoms, the crystal structure suggests that only the RRRR and SSSS enantiomers of the free ligand are obtained after recrystallisation from n-hexane. The structure indicates that the [Pb(THP-12-aneN4)]2+ cations are disordered, with 50% site occupancy by the RRRR and by the SSSS conformer.

Factors affecting stabilities of chelate, macrocyclic and macrobicyclic complexes in solution

Abstract The factors which contribute to the chelate, macrocyclic and cryptate effects are described. These include the dilution effect, translational entropy, intrinsic basicities of donor atoms, coulombic attractions and repulsions of charged ions and groups, and covalent character of the coordinate bonds. The reduction in hydration/solvation energies and the related coulombic repulsions of the donor atoms of multidentate ligands are related to preorganization of the ligands for complexation of metal ions. A not insignificant part of the chelate and macrocyclic effects is due to increase in the basicities of the donor atoms that occurs on ring formation, as well as to reduction of the steric repulsions of alkyl groups. The effects of ring size on stabilities are described. These factors are illustrated with stabilities of chelates, macrocyclic complexes and cryptates taken from the literature.

Enhanced Metal Ion Selectivity of 2,9-Di-(pyrid-2-yl)-1,10-phenanthroline and Its Use as a Fluorescent Sensor for Cadmium(II)

The metal ion complexing properties of the ligand DPP (2,9-di-(pyrid-2-yl)-1,10-phenanthroline) were studied by crystallography, fluorimetry, and UV-visible spectroscopy. Because DPP forms five-membered chelate rings, it will favor complexation with metal ions of an ionic radius close to 1.0 A. Metal ion complexation and accompanying selectivity of DPP is enhanced by the rigidity of the aromatic backbone of the ligand. Cd2+, with an ionic radius of 0.96 A, exhibits a strong CHEF (chelation enhanced fluorescence) effect with 10(-8) M DPP, and Cd2+ concentrations down to 10(-9) M can be detected. Other metal ions that cause a significant CHEF effect with DPP are Ca2+ (10(-3) M) and Na+ (1.0 M), whereas metal ions such as Zn2+, Pb2+, and Hg2+ cause no CHEF effect with DPP. The lack of a CHEF effect for Zn2+ relates to the inability of this small ion to contact all four donor atoms of DPP. The structures of [Cd(DPP)2](ClO4)2 (1), [Pb(DPP)(ClO4)2H2O] (2), and [Hg(DPP)(ClO4)2] (3) are reported. The Cd(II) in 1 is 8-coordinate with the Cd-N bonds to the outer pyridyl groups stretched by steric clashes between the o-hydrogens on these outer pyridyl groups and the central aromatic ring of the second DPP ligand. The 8-coordinate Pb(II) in 2 has two short Pb-N bonds to the two central nitrogens of DPP, with longer bonds to the outer N-donors. The coordination sphere around the Pb(II) is completed by a coordinated water molecule, and two coordinated ClO4(-) ions, with long Pb-O bonds to ClO4(-) oxygens, typical of a sterically active lone pair on Pb(II). The Hg(II) in 3 shows an 8-coordinate structure with the Hg(II) forming short Hg-N bonds to the outer pyridyl groups of DPP, whereas the other Hg-N and Hg-O bonds are rather long. The structures are discussed in terms of the fit of large metal ions to DPP with minimal steric strain. The UV-visible studies of the equilibria involving DPP and metal ions gave formation constants that show that DPP has a higher affinity for metal ions with an ionic radius close to 1.0 A, particularly Cd(II), Gd(III), and Bi(III), and low affinity for small metal ions such as Ni(II) and Zn(II). The complexes of several metal ions, such as Cd(II), Gd(III), and Pb(II), showed an equilibrium involving deprotonation of the complex at remarkably low pH values, which was attributed to deprotonation of coordinated water molecules according to: [M(DPP)(H2O)]n+ <==> [M(DPP)(OH)](n-1)+ + H+. The tendency to deprotonation of these DPP complexes at low pH is discussed in terms of the large hydrophobic surface of the coordinated DPP ligand destabilizing the hydration of coordinated water molecules and the build-up of charge on the metal ion in its DPP complex because of the inability of the coordinated DPP ligand to hydrogen bond with the solvent.

Possible Steric Control of the Relative Strength of Chelation Enhanced Fluorescence for Zinc(II) Compared to Cadmium(II): Metal Ion Complexing Properties of Tris(2-quinolylmethyl)amine, a Crystallographic, UV−Visible, and Fluorometric Study

The idea is examined that steric crowding in ligands can lead to diminution of the chelation enhanced fluorescence (CHEF) effect in complexes of the small Zn(II) ion as compared to the larger Cd(II) ion. Steric crowding is less severe for the larger ion and for the smaller Zn(II) ion leads to Zn-N bond length distortion, which allows some quenching of fluorescence by the photoinduced electron transfer (PET) mechanism. Some metal ion complexing properties of the ligand tris(2-quinolylmethyl)amine (TQA) are presented in support of the idea that more sterically efficient ligands, which lead to less M-N bond length distortion with the small Zn(II) ion, will lead to a greater CHEF effect with Zn(II) than Cd(II). The structures of [Zn(TQA)H(2)O](ClO(4))(2).1.5 H(2)O (1), ([Pb(TQA)(NO(3))(2)].C(2)H(5)OH) (2), ([Ag(TQA)(ClO(4))]) (3), and (TQA).C(2)H(5)OH (4) are reported. In 1, the Zn(II) is 5-coordinate, with four N-donors from the ligand and a water molecule making up the coordination sphere. The Zn-N bonds are all of normal length, showing that the level of steric crowding in 1 is not sufficient to cause significant Zn-N bond length distortion. This leads to the observation that, as expected, the CHEF effect in the Zn(II)/TQA complex is much stronger than that in the Cd(II)/TQA complex, in contrast to similar but more sterically crowded ligands, where the CHEF effect is stronger in the Cd(II) complex. The CHEF effect for TQA with the metal ions examined varies as Zn(II) >> Cd(II) >> Ni(II) > Pb(II) > Hg(II) > Cu(II). The structure of 2 shows an 8-coordinate Pb(II), with evidence of a stereochemically active lone pair, and normal Pb-N bond lengths. In 3, the Ag(I) is 5-coordinate, with four N-donors from the TQA and an oxygen from the perchlorate. The Ag(I) shows no distortion toward linear 2-coordinate geometry, and the Ag-N bonds fall slightly into the upper range for Ag-N bonds in 5-coordinate complexes. The structure of 4 shows the TQA ligand to be involved in pi-stacking between quinolyl groups from adjacent TQA molecules. Formation constants determined by UV-visible spectroscopy are reported in 0.1 M NaClO(4) at 25 degrees C for TQA with Zn(II), Cd(II), and Pb(II). When compared with other similar ligands, one sees that, as the level of steric crowding increases, the stability decreases most with the small Zn(II) ion and least with the large Pb(II) ion. This is in accordance with the idea that TQA has a moderate level of steric crowding and that steric crowding increases for TQA analogs tris(2-pyridylmethyl)amine (TPyA) < TQA < tris(6-methyl-2-pyridyl)amine (TMPyA).

The role of donor group orientation as a factor in metal ion recognition by ligands

Abstract Factors that control the metal ion complementarity of ligand architectures are described. These include cavity size, metal ion topography, and donor group orientation. Attention focuses on the last factor with a detailed discussion of how molecular mechanics has been used to investigate the role of donor group orientation in polyamine and polyether ligands.

The Chelate, Cryptate and Macrocyclic Effects

Abstract The chelate, macrocyclic, and cryptate effects are analyzed. It is concluded that for all three effects considerable stabilization is derived from the greater basicity induced in donor atoms as ethylene bridges are added. Further considerations of importance in these effects are (1) desolvation effects, where steric constraints to solvation of the donor atoms in the free ligand lead to increased complex stability, (2) enforced dipole-dipole repulsion in the ligand, which is relieved on complex formation, and (3) structural preorganization of the ligand such that the donor atoms in the free ligand are already correctly oriented for complex formation. Only for the chelate effect is entropy of paramount importance, where it is derived from a cratic effect. It is emphasized that the level of preorganization of macrocycles, and to a lesser extent cryptands, is much lower than commonly realized. Newly emerging types of more highly preorganized ligands are discussed.

Macrocycles and their selectivity for metal ions on the basis of size

The metal ion size selectivity of the oxygen— and nitrogen— donor macrocycles is examined. It is shown that the presence of the neutral oxygen donor in ligands leads to stronger complexation of large metal ions, with less favourable complexation of small, irrespective of whether the oxygen donor is part of a macrocyclic ring or not. Molecular Mechanics calculations indicate that the size—dependence of the complexing of metal ions by the neutral oxygen donors is controlled by a balance between the steric strain produced by the group bearing the oxygen donor, and its inductive effects. For tetraazamacrocycles the stability is controlled by the size of the chelate ring formed on complex—formation. Larger chelate rings lead to greater complex stabilisation for small metal ions, while larger metal ions show progressively greater complex destabilisation with larger chelate rings. This apparent paradox is also examined using molecular mechanics calculations. The use of neutral oxygen donors and chelate ring size to control metal ion size selectivity in ligand design is discussed.

Macrocyclic ligands with pendent amide and alcoholic oxygen donor groups

Abstract Bonding of the neutral oxygen donor to metal ions is discussed in relation to metal ion selectivity. Important factors are (a) inductive effects of alkyl groups attached to the oxygen donor atom, so that donor strength increases H 2 O 2 O, where R is an alkyl group, including ethylene or other alkyl groups forming bridges between donor atoms of multidentate ligands, and (b) size of the chelate ring formed, such that large metal ions achieve minimum strain energy when coordinated as part of five-membered chelate rings, while six-membered chelate rings favor small metal ions. Metal ions coordinate to alcohols or ethers lying in the same plane as the oxygen donor atom, and the two carbon or hydrogen atoms attached to the oxygen donor atom. This is discussed in terms of how the planarity of coordination about the oxygen donor atom alters selectivity patterns relative to neutral nitrogen donor atoms, where the geometry around the nitrogen coordinated to a metal ion is approximately tetrahedral. Addition of neutral oxygen donors as pendent alcoholic (2-hydroxyethyl and 2-hydroxypropyl) groups, or as amide (acetamide) groups, leads to changes in selectivity for metal ions that are as expected from arguments in terms of chelate ring size, and the donor strength of the alcoholic or amide oxygen. Thus, ligands based on cyclen (1,4,7,10-tetraazacyclododecane) with alcoholic and amide oxygen donor groups show large shifts in selectivity in favor of large metal ions such as Ca(II), Cd(II), or Pb(II). The potential of such ligands in treating Cd or Pb toxicity is discussed. The effect of addition of C-alkyl groups to the ethylene bridges of oxygen donor ligands is shown to produce shifts in selectivity in favor of small metal ions. This effect is particularly marked in novel ligands that contain cyclohexenyl bridges in place of ethylene bridges between the donor atoms. Such ligands are of potential interest in biomedical applications.

Affinity of the Highly Preorganized Ligand PDA (1,10-Phenanthroline-2,9-dicarboxylic acid) for Large Metal Ions of Higher Charge. A Crystallographic and Thermodynamic Study of PDA Complexes of Thorium(IV) and the Uranyl(VI) ion

The hydrothermal synthesis and structures of [UO2(PDA)] (1) and [Th(PDA)2(H2O)2].H2O (2) (PDA = 1,10-phenanthroline-2,9-dicarboxylic acid) are reported. 1 is orthorhombic, Pnma, a = 11.1318(7) A, b = 6.6926(4) A, c = 17.3114(12) A, V = 1289.71(14), Z = 4, R = 0.0313; 2 is triclinic, P1, a = 7.6190(15) A, b = 10.423(2) A, c = 17.367(4) A, alpha = 94.93(3) degrees , beta = 97.57(3) degrees , gamma = 109.26(3) degrees , V = 1278.3(4) A (3), Z = 2, R = 0.0654. The local geometry around the U in 1 is a pentagonal bipyramid with the two uranyl oxygens occupying the apical positions. The donor atoms in the plane comprise the four donor atoms from the PDA ligand (average U-N = 2.558 and U-O = 2.351 A) with the fifth site occupied by a bridging carboxylate oxygen from a neighboring UO2/PDA individual. The PDA ligand in 1 is exactly planar, with the U lying in the plane of the ligand. The latter planarity, as well as the near-ideal U-O and U-N bond lengths, and O-U-N and N-U-N bond angles within the chelate rings of 1 suggest that PDA binds to the uranyl cation in a low-strain manner. In 2, there are two PDA ligands bound to the Th (average Th-N = 2.694 and Th-O = 2.430 A) as well as two water molecules (Th-O = 2.473 and 2.532 A) to give the Th a coordination number of 10. The PDA ligands in 2 are bowed, with the Th lying out of the plane of the ligand. Molecular mechanics calculations suggest that the distortion of the PDA ligands in 2 arises because of steric crowding. UV spectroscopic studies of solutions containing 1:1 ratios of PDA and Th(4+) in 0.1 M NaClO4 at 25 degrees C indicate that log K1 for the Th(4+)/PDA complex is 25.7(9). The latter result confirms the previous prediction that complexes of PDA with metal ions of higher charge and an ionic radius of about 1.0 A such as Th(IV) would have remarkably high log K1 values with PDA. The origins of this very high stability are discussed in terms of a synergy between the pyridyl and the carboxylate donor groups of PDA. Metal ions of high charge normally bond poorly with pyridyl donors in aqueous solution because such metal ions require donor groups that are able to disperse charge to the solvent via hydrogen-bonding, which pyridyl groups are unable to do. In PDA, the carboxylates fulfill this need and so enable the high donor strength of the pyridyl groups of PDA to become apparent in the high log K1 for Th(IV) with PDA.