22 research outputs found
Investigations of copper(II) complexation by fragments of the FBP28 protein using isothermal titration (ITC) and differential scanning calorimetry (DSC)
Thiosemicarbazones : coordination properties in relation to biological activity
Thiosemicarbazones are considered to be potential therapeutics, because they
possess a broad range of biological properties including antitumor, antimalarial and
antimicrobial activity. Generally, the tiosemicarbazones coordinate to the metal
centre by means of an (N,S) bidentate mode, and when an additional coordinating
group is present, more diversified binding modes can occur such as a tridentate
(X,N,S) coordination fashion. The stability of the metal complexes formed with the
tiosemicarbazoness strongly depends on the character of the metal ion, the X-donor
atom of the additional functional group and the position and type of the substituents
at the tiosemicarbazones.
The most prominent representative of this family is the α(N)-heterocyclic Triapine
(3-aminopyridine- 2-carbaldehyde thiosemicarbazone; 3-AP), which is currently
undergoing different phase-I and -II clinical trials as an antitumor agent, and
demonstrates promising activity. Triapine is a very strong inhibitor of ribonucleotide
reductase, the rate determining enzyme in the supply of deoxyribonucleotides
for DNA synthesis required for cell proliferation. The mechanism of action involves
most probably the formation of an iron(II)–Triapine complex, which reacts with
molecular oxygen to result in the generation of reactive oxygen species. Subsequently,
these reactive oxygen species are responsible for the quenching of the active-site
tyrosyl radical of ribonucleotide reductase required for the enzymatic activity. As
a result, the coordination chemistry of iron complexes of tiosemicarbazones has
been receiving considerable attention.
This review describes the coordination chemistry of tiosemicarbazones, in particular
analogs of Triapine. The coordination compounds of d-block elements are
discussed with respect to their bonding and structures. Several of complexes are
mononuclear, with distorted tetrahedral, square planar, square pyramid or octahedral
as their common geometries. The metal-binding ability of STSC at physiological
pH was compared and shown.
Further, various biological applications with emphasis an anticancer activity
of the ligands/complexes are discussed in brief so as to indicate the importance of
ligands under consideration
Towards a new attenuating compound: a potentiometric, spectrophotometric and NMR equilibrium study on Fe(III), Al(III) and a new tetradentate mixed bisphosphonate-hydroxypiridinonate ligand
Coordination properties toward Fe(III) and Al(III) of a mixed bisphosphonate-hydroxypyridinonate ligand are presented. Potentiometric, spectrophotometric and NMR results allowed to conclude that Fe(III) and AI(III) coordination takes place on the pyridinone moiety. The high steric hindrance prevents the possibility of simultaneous coordination of both groups to the same metal ion. Quantum mechanical calculations confirm this finding allowing to determine the minimal length of the linker necessary for a stable conformation of complexes in which Fe(III) is coordinated both by pyridinone and bisphosphonate groups. (c) 2008 Elsevier Inc. All rights reserved
Bisphosphonate chelating agents: complexation of Fe(III) and Al(III) by 1-phenyl-1-hydroxymethylene bisphosphonate and its analogues
Bisphosphonate ligands were found to be very efficient chelating agents for both Al(III) and Fe(III) ions. Potentiometric and spectroscopic data allow evaluation of the coordination equilibria in the solutions containing 1-phenyl-1-hydroxymethylene bisphosphonate and its three analogues with Al(III) and Fe(III) ions. At pH below 4 the bis-complexes are formed, while above pH 4 the major species are equimolar, monomeric for Al(III) or dimeric for Fe(III) complexes. The large steric hindrance and high electric charge are the major factors influencing the complex stoichiometry. The formation of the dimeric Fe(III) with mu-oxo or mu-hydroxo bridges were supported by measurements of the magnetic moments using Evans' method. The stabilities of the complexes formed are higher than those found for deferiprone, L1, used in clinics as a chelating agent