Jan Rohovec

Nucleophilic reactivity of perhydro-3,6,9,12-tetraazacyclopenteno[1,3-f,g]acenaphthylene. A unified approach to N-monosubstituted and N,N′′-disubstituted cyclene derivatives

Abstract Perhydro-3,6,9,12-tetraazacyclopenteno[1,3- f,g ]acenaphthylene is readily mono- and dialkylated on nitrogen with alkyl bromides and iodides giving mono- and bis-quarternary ammonium salts. The title compound is a unified starting material for the preparation of cyclene based chelators.

Thermodynamic and kinetic study of copper(II) complexes with N-methylene(phenylphosphinic acid) derivatives of cyclen and cyclam

Equilibria of Cu(II) with newly synthetised ligands H4L1 and H4L2 were investigated by the glass electrode potentiometry at 25 degrees of Celsius and I = 0.1 M KNO3. A simple chemical model with metal:ligand molar ratio 1:1 was found in the systems. Presence of main species , CuL1 (log Beta = 20.37(4)) and CuL2 (log Beta = 17.19(2)) was also confirmed by MALDI-TOF/MS. The dissociation kinetics of the complexes was followed by spectrophotometry and mechanism of the dissociation was proposed. Activation parameters (activation enthalpy and entropy) of the dissociation were estimated. For Cu(II)-H4L1 system, the complex dissociation starts after protonization of phosphinic pendant arms and its mechasnism is similar to the decomplexation of [Cu(cyclen)]2+. The complex with H4L2 is kinetically much less stable and the proton transfer from phosphinic pendant arm to the azacycle plays a significant role in the reaction mechanism.

Synthesis, Crystal Structures, and Solution Properties ofN-Methylene(phenyl)phosphinic Acid Derivatives of Cyclen and Cyclam

Two phenylphosphinic acid derivatives of tetraaza surprisingly high. The complexes of Zn2+ and Cd2+ with (L1)4– and (L2)4– are less stable than those with other similar macrocycles, (1,4,7,10-tetraazacyclododecanetetrayl)tetrakis(methylene)tetrakis(phenylphosphinic acid)] (H4L) and ligands, which is in accordance with lower overall basicity of H4L and H4L. A pronounced drop in the stability of the (1,4,8,11-tetraazacyclotetradecanetetrayl)tetrakis(methylene)tetrakis(phenylphosphinic acid)] (H4L), were complexes of H4L can be explained by partial coordination of the ligand to the metal ions. The solution properties of the synthesised and the crystal structures of H4L and its bis(1adamantylammonium) salt were determined. In both the ligands were also investigated by 31P-NMR spectroscopy. The spectra observed suggest stable (on the NMR time scale) structures, the ring conformation is virtually the same and is stabilised by hydrogen bonds. Protonation constants of the conformations of the protonated ligands in solution. A comparison of NMR spectra in solution and CP/MAS-NMR acids and stability constants of their Zn2+ and Cd2+ complexes were determined pH-metrically at 25 °C and at spectra indicates that the structures of the conformers roughly correspond to the structures observed in the solid an ionic strength of 0.1 mol dm–3 (KNO3). The pKA values found for both the compounds are lower than those for their state. The conformations are stabilised by intramolecular hydrogen bonds and by hydrophobic interactions of carboxylic analogues and correspond to the expected electron-withdrawing ability of the –P(Ph)O2H moiety. The phenylphosphinic moieties. The conformers are stable even at 90 °C, but not in the presence of complexing metal ions. value pK1 of the last dissociation constant of H4L is

The cis/trans-isomerism on cobalt(III) complexes with 1,4,8,11-tetraazacyclotetradecane-1,8-bis(methylphosphonic acid)

Abstract The X-ray structure determinations show that 1,4,8,11-tetraazacyclotetradecane-1,8-bis(methylphosphonic) acid H4L forms both cis- and trans-O,O isomeric complexes with Co(III). Orientation of the other donor atoms indicates the formation of cis-O1,O2-trans-N1,N8-cis-O1,N4-[Co(HL)]. The kinetically preferred cis-isomer is easily formed due to the strong hydrogen bond between the neighboring phosphonic acid groups. The presence of the hydrogen bond in aqueous solution is confirmed by the value of pKa which increases by four orders of magnitude in comparison with the trans-isomer. Formation of the trans-[Co(HL)] occurs only after long heating of a Co(II) solution with the ligand under inert atmosphere before oxidation, which is explained by insertion of the Co(II) ion in the plane of nitrogen atoms of 1,4,8,11-tetraazacyclotetradecane.

Novel polymeric metal complexes of calix[4]arene-11,23-diphosphonic acid: synthesis and structure determination

New calixarene derivatives bearing two phosphonic acid groups, 25,27-dimethoxy-26,28-dihydroxycalix[4]arene-11,23-diphosphonic acid 3 and its tetraethyl ester 2 were synthesized. Their X-ray structures confirmed cone conformation of the molecules, more deformed for the ester due to bulky ethyl groups. Complexes [CaH 2 L(MeOH) 2 ]·4 MeOH ( 4 ) and [LnH 2 L(NO 3 )(H 2 O) 2 ]·2 H 2 O 2 MeOH (Ln=La(III), Pr(III), Nd(III), H 4 L=26,28-dihydroxy-25,27-dimethoxycalix[4]arene-11,23-diphosphonic acid) were also prepared. Structures of the Ca(II) complex 4 and Nd(III) complex 5 were determined by X-ray analysis. The structural motif of 4 is similar to that found for the free acid 3 . The calixarenes are linked by coordination of phosphonates to Ca(II) in a polymeric structure instead of a network of hydrogen bonds in 3 . Structure of 5 is different: four calixarene molecules are linked through coordination to Nd(III) in a supramolecular macroring, which forms a pore (approximately 17 A in diameter) penetrating through the structure.

Structures of MRI Contrast Agents in Solution

Contrast agents for magnetic resonance imaging are mainly Gd3+ complexes of octadentate polyaminopolycarboxylates and one water molecule in the first coordination sphere of the metal ion. Both the Ln3+ ion and the nitrogen atoms in these complexes may be chiral. Therefore, various isomers may occur for these complexes, which interconvert in aqueous solution. Here studies on the configurations and conformations of Ln3+ complexes of acyclic and cyclic ligands are reviewed. Furthermore, the structures of new generations of contrast agents that are able to target organs or to sense their biochemical environment are discussed. Molecular recognition is an important issue for these compounds.

Lanthanide complexes of a cyclen derivative with phenylphosphinic pendant arms for possible 1H and 31P MRI temperature sensitive probes

Lanthanide complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis[methylene(phenylphosphinic) acid] (H4L) were found to give a linear correlation of 1H and 31P NMR chemical shifts to temperature in the physiologically relevant temperature range, with dependencies comparable or better than those found for existing complexes; due to the greater hydrophobic character of the ligand the complexes may exhibit a different biodistribution in the body.

Complexing properties of phosphinic analogues of glycine

A series of aminomethylphosphinic acids H2NCH2PRO2H (R = H, Me, But or Ph) was synthesized and the acid–base and complexing properties with CoII, NiII and CuII were determined pH-metrically (25 °C, 0.1 mol dm–3 KNO3). The pKa values were found to increase from R = H to Ph, Me and But, as the –I effect decreases. The complex stability constants lie in the same order, except for R = H. The compound H2NCH2PHO2H (HL1) exhibits higher values than the ligands with methyl or phenyl substituents, probably due to better deformability of the PHO2– group and its better ability to form chelate rings. The complexes of H2NCH2P(Ph)O2H (HL4), H2NCH2P(Me)O2H (HL2) and H2NCH2P(But)O2H (HL3) with several transition metals were prepared and the crystal structures of [CuL42]1 and [Cu3L24][ClO4]22 were determined. The formation of chelate rings was observed in both structures; 1 forms dimers and 2 polymeric layers via the phosphinates.

Synthesis, characterisation and extraction behaviour of calix[4]arene-based phosphonic acids

Three new bis(phosphonic) acids were prepared by derivatization of p-tert-butylcalix[4]arene on the lower rim by –(CH2)xPO3H2 groups and were fully characterized by NMR spectroscopy; some of them were further investigated by X-ray analysis. The compounds obtained were tested as extractants for La3+, Eu3+, Yb3+ and Th4+ in 0.1–1 M HNO3. Structural details of the complex HLn(H2L1)2 where Ln = Y, La, Eu were elucidated by NMR techniques in solution. The extraction efficiencies decrease with increasing length of the CH2 spacer; the dependence is not monotonic, and an extraordinary selectivity was observed for Yb. The extraction efficiency of Ln3+ for all of the ligands studied increased significantly with decreasing ionic radius.

SYNTHESIS OF PHOSPHINIC ACID ANALOGUES OF GLYCYL–GLYCINE AND CRYSTAL STRUCTURE OF N-GLYCYL-AMINOMETHYL-(PHENYLPHOSPHINIC) ACID

ABSTRACT Phosphinic acid analogues of Gly-Gly, NH2CH2CONHCH2-P(R)O2H (R = Me, Ph, t-Bu), were synthesised by the active ester method from free aminomethylphosphinic acids purified on cation exchange resins. The crystal and molecular structure was determined for Gly–Gly(PPh)·H2O (R = Ph). The results point to similar bond parameters as were found for Gly–Gly and its phosphonic analogue Gly–Gly(P).