Alvaro S. de Sousa

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.

Metal Ion Complexing Properties of the Highly Preorganized Ligand 2,9-bis(Hydroxymethyl)-1,10-phenanthroline: A Crystallographic and Thermodynamic Study

Metal ion complexing properties of the ligand 2,9-bis(hydroxymethyl)-1,10-phenanthroline (PDALC) are reported. For PDALC, the rigid 1,10-phenanthroline backbone leads to high levels of preorganization and enhanced selectivity for larger metal ions with an ionic radius of about 1.0 A that can fit well into the cleft of the ligand. Structures of PDALC complexes with two larger metal ions, Ca(II) and Pb(II), are reported. [Ca(PDALC) 2](ClO 4) 2 ( 1) is triclinic, Pi, a = 7.646(3), b = 13.927(4), c = 14.859(5) (A), alpha = 72.976(6), beta = 89.731(6), mu = 78.895(6) degrees , V = 1482.5(8) A (3), Z = 2, R = 0.0818. [Pb(PDALC)(ClO 4) 2] ( 2) is triclinic, Pi, a = 8.84380(10), b = 9.0751(15), c = 12.178(2) (A), alpha = 74.427(3), beta = 78.403(13), mu = 80.053(11) degrees , V = 915.0(2) A (3), Z = 2, R = 0.0665. In 1, the Ca(II) is eight-coordinate, with an average Ca-N of 2.501 A and Ca-O of 2.422 A. The structure of 1 suggests that Ca(II) is coordinated in a very low-strain manner in the two PDALC ligands. In 2, Pb(II) appears to be eight-coordinate, with coordination of PDALC and four O donors from perchlorates bridging between neighboring Pb atoms. The Pb has very short Pb-N bonds averaging 2.486 A and Pb-O bonds to the alcoholic groups of PDALC of 2.617 A. It is suggested that the Pb(II) has a stereochemically active lone pair situated on the Pb(II) opposite the two N donors of the PDALC, and in line with this, the Pb-L bonds become longer as one moves around the Pb from the sites of the two N donors to the proposed position of the lone pair. There are two oxygen donors from two perchlorates, nearer the N donors, with shorter Pb-O lengths averaging 2.623 A. Two oxygens from perchlorates nearer the proposed site of the lone pair form very long Pb-O bond lengths averaging 3.01 A. The Pb(II) also appears to coordinate in the cleft of PDALC in a low-strain manner. Formation constants are reported for PDALC in 0.1 M NaClO 4 at 25.0 degrees C. These show that, relative to 1,10-phenanthroline, the hydroxymethyl groups of PDALC produce a significant stabilization for large metal ions such as Cd(II) or Pb(II) that are able to fit in the cleft of PDALC but destabilize the complexes of metal ions such as Ni(II) or Cu(II) that are too small for the cleft.

Complexation of Metal Ions of Higher Charge by the Highly Preorganized Tetradentate Ligand 2,9-Bis(hydroxymethyl)-1,10-Phenanthroline. A Crystallographic and Thermodynamic Study

The metal ion selectivity for M(III) (M = metal) ions exhibited by the highly preorganized ligand PDALC is investigated (PDALC = 2,9-bis(hydroxymethyl)-1,10-phenanthroline). The structures are reported of [Bi(PDALC)(H(2)O)(2)(ClO(4))(3)] x H(2)O (1), monoclinic, P2(1)/c, a = 12.8140(17), b = 19.242(3), c = 9.2917(12) A, beta = 91.763(2) degrees, V = 2289.9(5) A(3), Z = 4, R = 0.0428; [Th(PDALC)(NO(3))(4)] x 3 H(2)O (2), monoclinic, P2(1)/n, a = 7.876(3), b = 22.827(9), c = 12.324(5) A, beta = 94.651(6) degrees, V = 2208.4(15) A(3), Z = 4, R = 0.0669; [Cd(PDALC)(2)](ClO(4))(2) (3)), triclinic, P1, a = 7.5871(16), b = 13.884(3), c = 14.618(3) A, alpha = 74.081(2) degrees, beta = 88.422(2) degrees, gamma = 78.454(2) degrees, V = 1450.2(5) A(3), Z = 2, R = 0.0267. The Bi in 1 is best regarded as 9-coordinate, with four short bonds to the PDALC, and two short bonds to the coordinated water molecules, with three long bonds to perchlorate oxygens. The Bi-N bonds at 2.35 A are by a considerable margin the shortest Bi-N bonds to 1,10-phenanthroline (phen) type ligands, which is suggested to be due to the Bi adapting to the metal ion size requirements of PDALC. The Th(IV) in 2 is 12-coordinate, with four bonds to PDALC, and the four chelated nitrates, with close to normal bond lengths to the PDALC ligand. The Cd(II) in 3 is 8-coordinate, with Cd-N and Cd-O bonds that are similar to those found in other 8-coordinate Cd(II) complexes. The five known structures of PDALC complexes, including the three reported here, suggest that the M-N bonds to PDALC are quite easily varied in length in response to differing metal ion sizes, but that the M-O bonds are more constrained by the rigid ligand to be close to the ideal value of 2.50 A. The formation constants (log K(1)) for M(III) ions with PDALC show that for small metal ions such as Ga(III) and Fe(III), log K(1) is only slightly higher than for phen, suggesting that these metal ions are too small to coordinate to the alcoholic oxygen donors of PDALC. For larger metal ions such as Bi(III), Gd(III), Th(IV), and UO(2)(2+), log K(1) for PDALC is higher than log K(1) for phen by more than 5 log units, which stabilization is attributed to the fact that PDALC is preorganized for complexation with large metal ions with an ionic radius of about 1.0 A. The fluorescence of M(III) complexes of PDALC is discussed. PDALC free ligand gives fluorescence typical of phen ligands, with the protonated form giving a broad less intense band, and the non-protonated form of the ligand giving an intense structured set of bands. Large lanthanide ions without partially filled f-subshells, such as La(III), Lu(III), and also Y(III), give a fairly strong CHEF (chelation-enhanced fluorescence) effect, while those with partially filled f-subshells, such as Gd(III), Yb(III), and Tb(III), strongly quench the fluorescence of PDALC. A heavy element such as Bi(III) has strong spin-orbit coupling effects that act to quench the fluorescence of PDALC almost completely, which effect is enhanced by the covalence of the Bi-N bonds.

The synthesis and low-temperature X-ray study of bis[N,N,N′,N′-tetrakis-(2-hydroxyethyl)ethylenediamine]copper(II) perchlorate

Abstract The crystal structure of the product [Cu(H3L)ClO4]2 synthesized from an aqueous solution of L=N,N,N′,N′-tetrakis(2-hydroxyethyl)ethylenediamine (THEEN, C10H4N2O4) and an alkaline aqueous solution of (CuClO4)2 has been determined by X-ray diffraction methods. The copper complex of THEEN forms a dimeric species comprising two (CuH3L)+ monomers bonded by the formation of two metaloxygenmetal bridges. This dinuclear species lies across a crystallographic inversion center. The coordination sphere about the copper(II) ion is a highly distorted octahedron, with a distorted square planar configuration of two CuN bonds of 2.021 and 2.038 A and two CuO bonds of 1.940 and 1.959 A, respectively. Two longer axial CuO bonds of 2.674 and 2.332 A complete the distorted octahedral geometry.

The preparation of N-acetyl-Co(III)-microperoxidase-8 (NAcCoMP8) and its ligand substitution reactions: A comparison with aquacobalamin (vitamin B12a)

The synthesis of the Co(III) porphyrin octapeptide N-acetyl-Co(III) microperoxidase-8 (NAcCoMP8) is described. NAcCoMP8 provides a means of comparing and contrasting the chemistry of Co(III) porphyrins and corrins to assess the influence of the macrocycle. Log K values, and ΔH and ΔS, for the coordination of anionic (CN(-), N3(-), NO2(-), HSO3(-)) and neutral (pyridine, N-methylimidazole, methoxylamine and hydroxylamine) ligands by aquacobalamin (H2OCbl(+)) and NAcCoMP8 are reported. Anions bind more strongly to H2OCbl(+) than to NAcCoMP8 while the converse is true for the neutral ligands. Density Functional Theory (DFT) calculations and QTAIM analyses suggest the bonding between Co(III) and these ligands is predominantly ionic although anionic ligands induce a significant covalency, the extent of which is important for the stability of the complex. The CoL bond length (L=an anion) in a Co(III) corrin, while longer than in a Co(III) porphyrin, is shorter than might be expected as assessed from CoL bond lengths when L=neutral ligand. It is likely that this stems from coulombic interaction between L and the residual charge at the metal center (2+ in corrin; 1+ in porphyrin). Co(III) in H2OCbl(+) is more labile towards substitution by CN(-) than NAcCoMP8 but the converse is true when the entering ligand is neutral N-methylimidazole. The extent of participation of the incoming ligand in the transition state of the reaction is controlled by the log K value so the nature of the incoming ligand determines in which of these two macrocyclic systems Co(III) is the more labile.

Hydrogen-bonding controls the solid-state and enantiomeric comformations of the amino alcohol ligand 2-[(2-hydroxyethyl)amino]cyclohexanol

The crystal structure of the title compound, C(8)H(17)NO(2), consists of (R,R) and (S,S) enantiomeric pairs packed in adjacent double layers which are characterized by centrosymmetric hydrogen-bonded dimers, generated via N-H...O and O-H...O interactions, respectively. Intermolecular interactions, related to acceptor and donor molecule chirality, link the achiral double layers into tubular columns, which consist of a staggered hydrophilic inner core surrounded by a hydrophobic cycloalkyl outer surface and extend in the [011] direction.

N,N'-bis(2-hydroxycyclohexyl)-N,N'-bis(2-hydroxyethyl)ethane-1,2-diaminium dichloride.

The achiral meso form of the title compound, C(18)H(38)N(2)O(4)(2+)·2Cl(-), crystallizes to form undulating layers consisting of chains linked via weak hydroxyalkyl C-H...Cl contacts. The chains are characterized by centrosymmetric hydrogen-bonded dimers generated via N-H...Cl and hydroxycycloalkyl O-H...Cl interactions. trans-N-Alkyl bridges subdivide the chains into hydrophilic segments flanked by hydrophobic cycloalkyl stacks along [001].

Structure and stability of complexes of macrocyclic ligands bearing2-hydroxycyclohexyl groups. Structure of thecopper(II) complex of1-(2-hydroxycyclohexyl)-1,4,7,10-tetraazacyclododecane and thestrontium(II) complex of7,16-bis(2-hydroxycyclohexyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane

The compound 1-(2-hydroxycyclohexyl)-1,4,7,10-tetraazacyclododecane (L 1 ) and its complex [CuL 1 ][ClO 4 ] 2 1 have been prepared, as well as the complex [SrL 2 (H 2 O)][NO 3 ] 2 2 from the previously reported ligand L 2 (L 2 = D,L -7,16-bis(2-hydroxycyclohexyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctade cane). X-Ray studies of 1 and 2 gave for 1, triclinic, space group P, a = 8.632(1), b = 14.677(2), c = 17.797(4) A, α = 86.80(2), β = 78.71(2), γ = 83.32(1)°, Z = 4, R = 0.0606, while 2 gave monoclinic, space group Cc, a = 16.809(6), b = 8.889(2), c = 21.232(6) A, β = 101.47(2)°, Z = 4, R = 0.0314. The structure of 1 showed Cu–N and Cu–O bond lengths which were in the normal range. The structure shows some steric crowding of the co-ordinated ligand, with short H · · · H contacts between hydrogens on the cyclohexyl group and adjacent hydrogens on the macrocyclic ring. This acts to press the 2-hydroxycyclohexyl group towards the macrocyclic ring, and to have a compressive effect on the metal ion. The occurrence of 2 in space group Cc indicates spontaneous resolution of the complex into crystals with (R,R) or with (S,S) diastereomers of the ligand only. The Sr II is nine-co-ordinate, with a water molecule occupying a co-ordination site. An extensive hydrogen-bonding network involving hydrogens from the co-ordinated water on Sr II and nitrate oxygens, and hydrogens from the co-ordinated hydroxyls of the 2-hydroxycyclohexyl groups and nitrate oxygens, appears to be responsible for the spontaneous resolution. Ligands where ethylene bridges between donor atoms have been replaced by cyclohexanediyl bridges tend to show greater selectivity for smaller metal ions. This has been interpreted in terms of greater steric crowding on the outside of the ligand as the metal ion increases in size and decreases the curvature of the ligand. The structure of 2 shows six rather short H · · · H distances (2.05–2.2 A) between hydrogens on the cyclohexyl group, and on the macrocyclic ring, which are much shorter than similar contacts in complex 1, supporting this suggestion. The protonation constants (log K) of L 1 are 10.65, 9.51 and 4.03, while the formation constants (log K 1 ) are 13.85 (Zn II ), 14.58 (Cd II ) and 11.40 (Pb II ), all in 0.1 mol dm -3 NaNO 3 at 25 °C. The effect of the 2-hydroxycyclohexenyl bridge on the stability of complexes is discussed.

Bis­(2-hy­droxy­eth­yl)ammonium 2-bromo­phenolate

In the crystal structure of the 1:1 title salt, C4H12NO2 +·C6H4BrO−, hydrogen-bonding interactions originate from the ammonium cation, which adopts a syn conformation. A gauche relationship between the C—O and C—N bonds of the 2-hydroxyethyl fragments also facilitates O—H⋯O interactions of bis(2-hydroxyethyl)ammonium cation chains to phenolate O atoms. The resulting double-ion chains along [100] are further linked by N—H⋯O interactions, forming chains parallel to [110].

Hydrogen-bond inter-actions in morpholinium bromide.

In the title compound, C4H10NO+·Br−, which was synthesized by dehydration of diethanolamine with HBr, morpholinium and bromide ions are linked into chains by N—H⋯Br hydrogen bonds describing a C 2 1(4) graph-set motif. Weaker bifurcated N—H⋯Br interactions join centrosymmetrically related chains through alternating binary graph-set R 4 2(8) and R 2 2(4) motifs, to form ladders along [100]. In addition, C—H⋯O interactions between centrosymmetric morpholinium cations link ladders, via (8) motifs, to yield sheets parallel to (101), which in turn are crosslinked by weak C—H⋯O interactions, related across a glide plane, to form a three-dimensional network.