Srećko R. Trifunović

TRANSITION METAL COMPLEXES WITH EDDA-TYPE LIGANDS—A REVIEW

ABSTRACT The review summarizes the results of recent studies on edda-type metal complexes. It focuses on work published during the period 1984–2001. The metals include are Co, Cr, Cu, Ni, Zn, Mn, Sn, Fe, V, Rh, Pt, Ru, whereas edda-type represents ethylenediamine-N,N′-diacetate, ethylenediamine-N,N-di-acetate, N,N′-dimethylethylenediamine-N,N′-diacetate, N,N′-diethylethylenediamine-N,N′-diacetate, 1,2-cyclo-hexanediamine-N,N′-diacetate, N,N′-dimethyl-1,2-cyclohexanediamine-N,N′-diacetate, ethylenediamine-N,N′-di-3-propionate, N,N′-dimethylethylenediamine-N,N′-di-3-propionate, ethylenediamine-N,N′-di-S-α-propionate, N,N′-dimethyl-ethylenediamine-N,N′-di-α-propionate, 1,3-propanediamine-N,N′-diacetate (trimethylenediamine-N,N′-diacetate), 1,3-propanediamine-N,N′-di-3-propionate (trimethylenediamine-N,N′-di-3-propionate), N,N′-dimethylethylenediamine-N,N′-di-α-butyrate, N,N′-diethylethylenediamine-N,N′-di-α-butyrate, 1-diethylenetriamineacetate (8-amino-3,6-diazao-ctanoate), ethylenepropylenetriamineacetate (9-amino-3,6-diazaoc- tanoate), dipropylenetriamineacetate (10-amino-3,6-diazaoc-tanoate), N,N-bis(2-aminoethyl)glycinate, N,N-bis(3-aminopropyl)glycinate, N-(2-aminoethyl)-N-(3-aminopropyl)glycinate, N-(2-aminoethyl)iminodiacetate (N-(2-aminoethyl)-N-carboxymethylglycine), N-(3-aminopropyl)imino diacetate tetradentate ligands. This paper provides a review of these complexes including their syntheses and X-ray crystal structures, spectroscopic (IR, Raman, NMR, ESR, electronic absorption and CD) measurements, electrochemistry, kinetic and thermodynamic information, magnetic properties, hydrolysis phenomena as well as chromatographic studies.

Synthesis, characterization and antitumor activity of polymeric copper(II) complexes with thiosemicarbazones of 3-methyl-5-oxo-1-phenyl-3-pyrazolin-4-carboxaldehyde and 5-oxo-3-phenyl-3-pyrazolin-4-carboxaldehyde.

New polymeric copper(II) complexes with two tridentate ONS thiosemicarbazone ligands containing substituted pyrazolone moiety were synthesized and characterized by means of spectroscopic, electrochemical and crystallographic techniques. While both ligands exist as different tautomers in the solid state and DMSO-d(6) solution, Cu(II) ion coordinates the ligands from the same tautomeric form with square-pyramidal geometry around each Cu atom. In the crystal structures, the copper(II) complex cation forms polymeric chains {[Cu(L)Cl](+)}(n) with a bridging chlorine atom. One of the complexes was found to have a significantly higher cytotoxic potential in comparison with cisplatin in inhibition of several cell lines (HL60, REH, C6, L929 and B16). The results obtained on the basis of flow cytometry indicated that apoptosis could be possible mechanism of cell death.

Synthesis and characterization of hexadentate cobalt(III) complexes with novel edta-type ligands Part 2. Circular dichroism of the trans(O5O6) and trans(O6) isomers of a cobalt(III) complex of 1,3-propanediamine-N,N′-diacetic-N,N′-di-3-propionic acid

Abstract Cobalt(III) complexes with the hexadentate ligand, 1,3-propanediamine-N,N′-diacetate-N,N′-di-3-propionate ion (1,3-pddadp) were prepared, chromatographically separated into two geometrical isomers with respect to the NO chelate ring size [trans(O5O6) and trans(O6)], and resolved. The 1H NMR, electronic absorption and circular dichroism (CD) spectra were used to characterize the complexes. The splitting of the T1g(Oh) band of the trans(O6-[Co(1,3-pddadp)]− complex indicates that the tetragonal field is enhanced, relative to the fields in other [Co(edta)]− -type complexes reported. The (+)546-trans(O5O6)-[Co(1,3-pddadp)]− and (+)546-trans(O6)-[Co(1,3- pddadp)]− complexes with a positive CD peak at lowest energy in the first spin-allowed d-d absorption band region are tentatively assigned the Λ absolute configuration. Preliminary results of a crystallographic study of the Ktrans(O6)-[Co(1,3-pddadp)]·3H2O confirm the assignments of geometrical isomers of the complexes.

Proton and carbon-13 NMR studies of cis-eq- and trans-eq-ethylenediamine-N,N,N′-triacetatocobalt(III) and cis-eq-N-methylethylenediamine-N,N,′N′-triacetatocobaltate(III). Crystal structure of NH4cis-eq-[Co(ed3a)CN]

Abstract The complexes K cis - eq -[Co(ed3a)CN], K cis - eq -[Co(med3a)CN)], and K trans - eq -[Co(ed3a)CN] were synthesized and characterized. The 1 H and 13 C NMR spectra obtained with a 300 MHz spectrometer are reported and compared to corresponding aqua and nitro complexes. The PMR spectra show good resolution for all protons, including those of the ethylenediamine backbone. The NMR spectra of the cyano complexes are most similar to those of the corresponding nitro complexes. The major changes in the 13 C NMR spectra can be explained based on β-substituent effects involving the N-methyl group or conversion from the cis - eq to the trans - eq isomers. Racemic NH 4 [Co(ed3a)CN]·2H 2 O·0.5CH 3 OH was found to be triclinic, P -1 with the cell dimensions: a = 6.597(2), b = 7.783(4), c = 15.72(1) A, α = 88.63(5), β = 85.55(5), and γ = 69.89(4)°. There are two molecules in the unit cell.

PREPARATION AND CHARACTERIZATION OF FACIAL AND MERIDIONAL ISOMERS OF UNS-CIS-(ETHYLENEDIAMINE-N,N'-DI-3-PROPIONATO)(GLYCINATO)COBALT(III) SEMIHYDRATE

Abstract Both theoretically possible geometrical isomers, facial and meridional, of uns-cis-(ethylenediamine-N, N′-di-3-propionato)(glycinato)cobalt(III) semi hydrate have been prepared by reaction of sodium uns-cis-(ethylenediamine-N, N′-di-3-propionato) (carbonato) cobaltate(III) with glycine at 75°C. The complexes have been isolated chromatographically and characterized by elemental analysis, electron absorption, infrared and nuclear magnetic spectra.

Square-planar copper(II) complexes with a novel tetradentate amido-carboxylate ligand. Crystal structure of [Co(H2O)6][Cu(mda)] · 2H2O

A novel O—N—N—O-type tetradentate ligand H4mda (H4mda = malamido-N,N′-diacetic acid) and the corresponding square-planar copper(II) complexes have been prepared and characterized. The mda4− ligand coordinates to the copper(II) ion via two pairs of deprotonated ligating atoms (two carboxylate oxygens and two deprotonated amide nitrogens) with in-plane square chelation. A four-coordinate, square-planar geometry has been established crystallographically for the [Co(H2O)6][Cu(mda)] · 2H2O complex. Structural data correlating the square-planar geometry of the [Cu(mda)]2− unit are discussed in relation to information obtained for similar complexes. The i.r., electronic, absorption and reflectance spectra of the complexes are analysed in comparison with related complexes of known geometries.

Synthesis, characterization and cytotoxicity of a new palladium(II) complex with a coumarine-derived ligand

The new coumarine derivative, 3-(1-(2-hydroxyethylamino)ethylidene)chroman-2,4--dione, and corresponding palladium(II) complex have been synthesized and characterized by microanalysis, infrared, (1)H and (13)C NMR spectroscopy. The proposed structure of the complex was confirmed on the basis of the X-ray structural study. The palladium(II) complex decreased viability of L929 mouse fibrosarcoma, U251 human glioma and B16 mouse melanoma cell lines in a dose dependent manner, while its ligand exhibited no significant cytotoxicity. The cytotoxic effect of the complex was comparable to that of cisplatin, and mediated by apoptosis associated with oxidative stress, mitochondrial depolarization and caspase activation. Therefore, our results indicate that newly synthesized palladium(II) complex might be a potential candidate for anticancer therapy.

Diamine-N,N′-diacetatochromate(III) complexes with oxalate and malonate anions. Crystal structure of (−)589-[Co(en)2(C2O4)](−)546-[Cr(1,3-pdda)(mal)]·H2O

Abstract The uns-cis-[Cr(1,3-pdda)(L)]− complexes (1,3- pdda = 1,3-propanediamine-N,N′-diacetate; L = oxalate or malonate) were prepared and resolved. The corresponding s-cis-[Cr(edda)L]− complexes (edda = ethylenediamine-N,N′-diacetate) have been partially resolved. The infrared absorption and circular dichroism (CD) spectra are reported. Rotational strengths of the uns-cis-[Cr(1,3-pdda)(L)]− complexes decrease with increasing chelate ring size of the bidentate anionic ligands. (−)589-[Co(en)2- (C2O4)]uns-cis-(−)546-[Cr(1,3-pdda)(mal)]·H2O crystallizes in the space group P21 of the monoclinic crystal system with a = 7.832(3), b = 14.207(6), c = 10.801(3) A, β = 98.46(3)° and Z = 2. In the anionic chromium complex, the six-membered diamine ring assumes the stable chair conformation; the equatorial glycinate ring is puckered; and the axial glycinate ring is in the ‘envelope’ conformation. The absolute configuration of the chromium complex ion is ΔΔΔΛ.

Low-dimensional compounds containing bioactive ligands. Part VI: Synthesis, structures, in vitro DNA binding, antimicrobial and anticancer properties of first row transition metal complexes with 5-chloro-quinolin-8-ol

A series of new 3d metal complexes with 5-chloro-quinolin-8-ol (ClQ), [Mn(ClQ)2] (1), [Fe(ClQ)3] (2), [Co(ClQ)2(H2O)2] (3), [Ni(ClQ)2(H2O)2] (4), [Cu(ClQ)2] (5), [Zn(ClQ)2(H2O)2] (6), [Mn(ClQ)3]·DMF (7) and [Co(ClQ)3]·DMF·(EtOH)0.35 (8) (DMF=N,N-dimethylformamide), has been synthesized and characterized by elemental analysis, IR spectroscopy and TG-DTA thermal analysis. X-ray structure analysis of 7 and 8 revealed that these molecular complexes contain three chelate ClQ molecules coordinated to the central atoms in a deformed octahedral geometry and free space between the complex units is filled by solvated DMF and ethanol molecules. Antimicrobial activity of 1-6 was tested by determining the minimum inhibitory concentration and minimum microbicidal concentration against 12 strains of bacteria and 5 strains of fungi. The intensity of antimicrobial action varies depending on the group of microorganism and can be sorted: 1>ClQ>6>3/4>2>5. Complexes 1-6 exhibit high cytotoxic activity against MDA-MB, HCT-116 and A549 cancer cell lines. Among them, complex 2 is significantly more cytotoxic against MDA-MB cells than cisplatin at all tested concentrations and is not cytotoxic against control mesenchymal stem cells indicating that this complex seems to be a good candidate for future pharmacological evaluation. Interaction of 1-6 with DNA was investigated using UV-VIS spectroscopy, fluorescence spectroscopy and agarose gel electrophoresis. The binding studies indicate that 1-6 can interact with CT-DNA through intercalation; complex 2 has the highest binding affinity. Moreover, complexes 1-6 inhibit the catalytic activity of topoisomerase I.

Synthesis and characterization of hexadentate cobalt(III) complexes with new edta-type ligands. Part 4. Circular dichroism of the trans(O5O6) isomer of a cobalt(III) complex of 1,3-propanediamine-N, N, N′-triacetic-N′-3-propionic acid

Abstract One of two geometrical isomers of the hexadentate cobalt(III) complex with 1,3-propanediamine- N , N , N ′-triacetate- N ′-3-propionate ion (1,3-pd3ap) has been prepared and resolved. The NMR, electronic absorption and circular dichroism (CD) spectra were used to characterize the complex. The 1 H and 13 C NMR spectra of this geometrical isomer indicate that its six-membered propionate chelate ring is bound axially to the cobalt(III) ion, trans (O 5 O o )-[Co(1,3-pd3ap)] − . The (−) 546 - trans (O 5 O o )-[Co(1,3-pd3ap)] − complex, with a positive CD peak at lowest energy in the first spin-allowed absorption band region is tentatively assigned the Λ absolute configuration. Spectral data for this complex are discussed in relation to those of other [Co(edta-type)] − complexes which vary the size of carboxylate arms in the same way but maintain a six-membered diamine ring.