Kevin P. Wainwright

Synthetic and structural aspects of the chemistry of saturated polyaza macrocyclic ligands bearing pendant coordinating groups attached to nitrogen

Abstract Developments in the synthetic and structural aspects of the chemistry of saturated polyaza macrocyclic ligands bearing pendant coordinating groups attached to nitrogen, that have occurred since 1989, have been reviewed. The review is organised in terms of the types of reaction that have been used on saturated triaza, tetraaza. pentaaza, and hexaaza macrocyclic ligands to attach pendant donor groups to the nitrogen atoms. Where structural studies have beenundertaken on metal complexes of these ligands the results of these studies are described.

Applications for polyaza macrocycles with nitrogen-attached pendant arms

Publisher Summary This chapter focuses on the complexes of nitrogen-attached pendant-arm polyaza macrocyclic ligands, and discusses the potential of Zn(II) complexes of pendant-arm polyaza macrocycles to act as models for the hydrolytic Zn(II)-containing enzymes. The chapter also explores how different types of pendant arm have been introduced onto a macrocyclic framework and it has been possible to utilize their presence to elicit information of relevance to a particular group of enzymes. The enzyme groups studied using pendant-arm macrocycles have been the alkaline phosphatases and the class II aldolases. Enhancing the cell membrane-crossing capability of the Zn(II)-cyclen-based nucleobase recognition reagents is tackled by using pendant-arm macrocycles with a single long-chain alkyl pendant. The approach is discussed using pendant-arm macrocycles to build the observation that [Zn(cyclen)] 2+ bindsdeoxythymidine (dT) and uridine (U) selectively from a mixture of all nucleosides in the aqueous solution at physiological pH, with binding constants of 10 5.6 and 10 5.2 M -1 , respectively.

Synthesis, structure and complexing capabilities of N,N′,N′′,N′′′-tetrakis(3-hydroxypropyl)cyclam

Abstract The synthesis of the new pendant arm macrocyclic ligand N,N′,N′′,N′′′ -tetrakis(3-hydroxypropyl)cyclam (THPC-14) has been accomplished, in quantitative yield, through the high pressure reaction of 1,4,8,11-tetraazacyclotetradecane (cyclam) with trimethylene oxide (oxetane). The molecular and crystal structure of this compound, which have been determined by X-ray crystallography, show the presence of both intermolecular and intermolecular hydrogen bonding, the former of which, together with an RSSR pattern of chiralities at the nitrogen atoms (the trans-IV configuration), preorganise the ligand unfavourably towards complexation. Formation constants have been determined for complexes of the ligand with Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ , Cd 2+ Hg 2+ and Pb 2+ by glass electrode potentiometry. In all cases the [M(THPC-14] 2+ complex is less stable than the complex formed from the related ligand N,N′,N′′,N′′′ -tetrakis(2-hydroxyethyl)cyclam (THEC-14), a fact which can be attributed to the formation of six-membered chelate rings by the pendant arms rather than five-membered chelate rings. Isolation of the octahedral complexes [Ni(THPC-14)](ClO 4 ) 2 and [Ni(THPC14)(NCS) 2 ] and a study of their spectral and magnetic properties indicates that pendant hydroxyl coordination occurs, but that this bonding is relatively weak facilitating easy substitution by isothiocyanate.

Synthesis and crystal structure determination of some novel zinc(II) macrocyclic heptaaza Schiff-base complexes with two 2-aminoethyl pendant arms

Abstract Three heptadentate Zn(II) macrocyclic bis(pendant donor) Schiff-base complexes, [Zn Ln](ClO4)2 (n=5, 6, 7) have been prepared via the Zn(II) templated [1+1] condensation of 2,6-diacetylpyridine with branched hexaamines, and characterised by X-ray diffraction, IR, 1H and 13C NMR spectroscopy. The ligands are 15-, 16- and 17-membered pentaaza macrocycles with two pendant 2-aminoethyl groups [L5=2,13-dimethyl-6,9-bis(2-aminoethyl)-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18), 2, 12, 14, 16-pentaene, L6=2,14-dimethyl-6,10-bis(2-aminoethyl)-3,6,10,13,19-pentaazabicyclo[13.3.1]nonadeca-1(19), 2, 13, 15, 17-pentaene and L7=2,15-dimethyl-6,11-bis(2-aminoethyl)-3,6,11,14,20-pentaazabicyclo[14.3.1]eicosa-1(20),2,14,16,18-pentaene]. The crystal structure of [Zn L5](ClO4)2, was determined by X-ray diffraction and showed that the complex cation that had formed consisted of a pentagonal bipyramidally coordinated Zn(II) ion, centrally located in a pentaaza macrocycle, with two pendant amines coordinating on opposite sides of a plane defined by the macrocycle and the metal ion. The spectroscopic characterisation of the three complexes is consistent with them all having this basic structure.

Complexation of cobalt(II), nickel(II) and copper(II) by the pendant arm macrocyclic ligand N,N′,N″,N‴-tetrakis(2-hydroxyethyl)-l,4,8,11-tetraazacyclotetradecane

Abstract A stopped-flow spectrophotometric study of the complexation of Co2+ and Ni2+ by the pendant arm ligand, N, N′, N″, N‴-tetrakis(2-hydroxyethyl)-1,4,8,11-tetraazacyclotetradecane (L2), in aqueous solution at pH 6.80, I=1.50 (NaNO3) and 298.2 K yields the rate constants, kLH′=880 and 116 dm3 mol−1 s−1 for the complexation of Co2+ and Ni2+, respectively, by the monoprotonated ligand, L2H+. In aqueous HNO3, the decomplexation of [ML2]2+ is characterized by: kobs=k0+k1K1a[H+]/1+K1a[H+] where at 298.2 K, k0=0.21, ≈0 and ≈0 s−1, k1=151, 0.160 and 6.07 s−1, and K1a=5.2, 83 and 0.67 dm3 mol−1, respectively, when M2+=Co2+, Ni2+ and Cu2+. The effect of the pendant arms on the complexation and decomplexation processes are considered through a comparison of these data with those for 1,4,8,11-tetraazacyclotetradecane and related ligands.

An Update on the Use of the Sodium Rhodizonate Test for the Detection of Lead Originating from Firearm Discharges

We have made a comprehensive investigation of the chemistry associated with the Sodium Rhodizonate Test for particulate lead deposited on surfaces as a consequence of a firearm discharge. This has been directed at addressing some of the problems that have hitherto compromised the value of this test to forensic science. In particular, we have found that aqueous solutions of sodium rhodizonate are considerably more stable if stored below pH 3. The rhodizonate dianion is then diprotonated, forming rhodizonic acid, and the half-life of the solution increases from about one hour to about ten hours. By ensuring that the area to be examined is pretreated with tartrate buffer so that its pH is adjusted to 2.8 prior to treatment with rhodizonic acid, the formation of a nondiagnostic purple complex, instead of the desired scarlet complex, is avoided. Whereas the scarlet complex changes to a blue-violet complex, upon secondary treatment with 5% HCl, which is diagnostic of the presence of lead, the purple complex decolorises completely under these conditions and thus its formation represents wastage of lead from within the test area and is associated with the fading problem that has previously plagued the test. The fading of the blue-violet complex can be eliminated by removing excess HCl, by means of a hair drier once the color has fully developed.

Structural requirements for rapid metal ion ingress into hydroxyethylated tetraaza macrocycles

Abstract Synthesis of two new bis(2-hydroxyethyl)_substituted cyclam (1,4,8,11-tetraazacyclotetradecane) 1,4-bis(2-hydroxyethyl)-8,11-dimethylcyclam (1,4-DMHEC-14) and 1,11-bis(2-hydroxyethyl)-4,8-dimethylcyclam (1,11-DMHEC-14), has enabled a study of the effects of partial hydroxyethylation of the nitrogen atoms in a macrocyclic ligand framework to be made. The ligands were synthesised through the reaction of ethylene oxide with the appropriately methylated cyclam precursor. Stability constants for complexes of these ligands with Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ Cd 2+ Hg 2+ and Pb 2+ have been measured by potentiometric titration and are generally intermediate between those shown by tetramethylcyclam (TMC-14) and tetrakis(2-hydroxyethyl)cyclam (THEC-14), consistent with a lower level of ligand stabilisation through internal hydrogen bond formation than in THEC-14. Equilibration times noted during the potentiometric titrations indicate that these bis(2-hydroxyethyl) ligands, like THEC-14 and unlike TMC-14, facilitate rapid entry of the metal ion into the macrocyclic annulus demonstrating that two pendant 2-hydroxyethyl arms, when located on adjacent nitrogen atoms, are sufficient to generate facilitated entry. The crystal structures of both [Ni(1,4-DMHEC-14)](ClO 4 ) 2 and [Ni(l,II-DMHEC14)](ClO 4 ) 2 have been determined by a combined molecular mechanics and X-ray crystallography study and show that in each isomer both pendant donors are coordinated in a trans -relationship, in addition to the four nitrogen atoms, giving rise to octahedral stereochemistry. In the former case the ligand is in the trans -III configuration whereas the latter complex has a trans -II geometry.

Chemistry of structurally developed macrocycles. Part 1. Complexation properties of NN′N″N‴-tetra(2-cyanoethyl)-1,4,8,11-tetra-azacyclotetradecane with nickel(II)

Reaction of 1,4,8,11-tetra-azacyclotetradecane (cyclam) with excess of acrylonitrile yields quantitatively the tetracyanoethylated product. In the presence of donor anions this potentially eight-co-ordiante ligand behaves as a quadridentate ligand towards nickel(II) binding through the tertiary amine donors alone. The resulting complexes are generally five-co-ordinate (six-co-ordinate with NCS–) having the ligand in a partially folded configuration. With perchlorate as anion a polymeric nickel(II) complex is formed which consists of five-co-ordinate metal centres linked together by intermolecularly bridging nitriles. Attempts to hydrolyse the nitrile groups of the free ligand to produce the tetra-amide or tetracarboxylic acid were unsuccessful. However, hydrolysis of the tetranitrile when co-ordinated to nickel(II) proceeds at neutral pH producing an octahedral complex containing the co-ordinated tetra-amide.

Equilibrium and kinetic studies of complexes of the pendant donor macrocycles N,N′,N″,N‴-tetrakis(2-hydroxyethyl)-1,4,7,10-tetraazacyclododecane (THEC-12) and N, N′, N″, N‴-tetrakis(2-hydroxyethyl)-1,4,8,12-tetraazacyclopentadecane (THEC-15)

Abstract Investigations of the thermodynamic and kinetic properties of the Co2+, Ni2+, Cu2+, Zn2+, Cd2+ and Pb2+ complexes of N, N′, N″, N‴-tetrakis(2-hydroxyethyl)-1,4,7,10-tetraazacyclododecane (THEC-12) and the newly synthesised N, N′, N″, N‴-tetrakis(2-hydroxyethyl)-1,4,8,12-tetraazacyclopentadecane (THEC-15) have been undertaken. Formation constants for the ML2+ complexes indicate that the hydroxyethyl groups cause significant destabilisation of the complexes with respect to those of the non-hydroxyethylated macrocycles. For decomplexation of [M(THEC-12)]2+ in aqueous HNO3 the observed rate constants =kobs = kO + kH[H+], where at 298.2 K, kO = (3.06 ± 1.86) × 10−5 s−1 when M  Co, kO ≈ s−1 when M  Ni and Cu, and 105 kH = 61.4 ± 2.9, 5.78 ± 1.42 and 2.81 ± 0.09 dm3 mol−1 s−1 when M  Co, Ni and Cu, respectively. For [M(THEC-15)]2+, decomplexation is very slow with t 1 2 >24 h (in 1.00 mol dm−3 HNO3) when M  Co and Ni, but considerably faster with t 1 2 ≈ s (1.00 mol dm−3 HNO 3) when M  Cu.

Synthesis, X-ray Characterization, NMR and Ab Initio Molecular-Orbital Studies of some Cadmium(II) Macrocyclic Schiff-Base Complexes with Two 2-Aminoethyl Pendant Arms

Three new pendant arm Schiff-base macrocyclic complexes, [CdLn]2+ (n = 5, 6, 7), have been prepared via cyclocondensation of 2,6-diacetylpyridine with three different branched hexaamines in the presence of Cd(II). The ligands are 15-, 16- and 17-membered pentaaza macrocycles having two 2-aminoethyl pendant arms [L5 = 2,13-dimethyl-6,9-bis(aminoethyl)-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),2,12,14,16-pentaene, L6 = 2,14-dimethyl-6,10-bis(aminoethyl)-3,6,10,13,19-pentaazabicyclo[13.3.1]nonadeca-1(19),2,13,15,17-pentaene and L7 = 2,15-dimethyl-6,11-bis(aminoethyl)-3,6,11,14,20-pentaazabicyclo[14.3.1]eicosa-1(20),2,14,16,18-pentaene]. All complexes were investigated by IR, 1H and 13C NMR, COSY(H,H) and HETCOR(H,C) spectroscopy and X-ray diffraction. In the solid state structure of each complex the Cd(II) ion is situated centrally within an approximately planar pentaaza macrocyclic ring, binding to the five nitrogen atoms, and also to the two pendant amines which are located on opposite sides of the macrocyclic plane. ab initio HF-MO calculations using a standard 3-21G* basis set have been used to verify that these similar basic structures correspond to energy minima in the gas phase.