Synthesis, structure and antimicrobial activity of metal(II/III) complexes with 2,2-dimethyl-1,3-propanediamine-N,N, Nʼ, Nʼ-tetraacetate

U cilju ispitivanja uticaja strukturnih modifikacija u 1,3-pdta ligandu na strukturne osobine i biološku aktivnost metal(II/III) kompleksa u okviru ove doktorske disertacije, opisana je sinteza 2,2-dimetil-1,3-propandiamin-N,N,N’,N’- tetraacetata (2,2-diMe-1,3-pdta), kao i odgovarajućih kompleksa magnezijuma(II), mangana(II), kobalta(II/III), hroma(III) i kadmijuma(II). Opisana je i strukturna karakterizacija sintetisanih kompleksa, kao i njihova antifungalna i antibakterijska aktivnost. Takođe, u cilju definisanja terapeutskog potencijala sintetisanih kompleksa, ispitivana je njihova antiproliferativna aktivnost prema zdravoj ćelijskoj liniji fibroblasta pluća (MRC-5). Strukturne osobine i antimikrobna aktivnost sintetisanih [M(2,2-diMe-1,3- pdta)]n– kompleksa su poređene sa odgovarajućim osobinama analognih [M(1,3-pdta)]n– (1,3-propandiamin-N,N,N’,N’-tetraacetat) i [M(1,3-pndta)]n– ((±)-1,3-pentandiaminN,N,N’,N’-tetraacetat) kompleksa. U prvom delu doktorske disertacije opisan je značaj kompleksnih jedinjenja metala sa diaminotetrakarboksilatnim ligandima i dat je prikaz kompleksa metala sa ligandima 1,3-pdta-tipa, koji su do sada sintetisani i strukturno okarakterisani primenom rendgenske strukturne analize. Postupci za sintezu [M(2,2-diMe-1,3-pdta)]n– kompleksa (M = Mg(II), Mn(II), Cd(II), Co(II/III) i Cr(III)) i metode za njihovu strukturnu karakterizaciju i biološko ispitivanje opisani su u drugom delu disetracije, dok su u trećem delu, koji se odnosi na Diskusiju rezultata prikazani rezultati spektroskopske i kristalografske karakterizacije sintetisanih [M(2,2- diMe-1,3-pdta)]n– (M = Mg(II), Mn(II), Cd(II), Co(II/III) i Cr(III)) kompleksa, kao i rezultati dobijeni ispitivanjem njihove antimikrobne aktivnosti i toksičnosti.In order to investigate the influence of structural modifications of the 1,3-pdta ligand on the structural properties and biological activity of the metal(II/III) complexes, within this doctoral dissertation, the synthesis of 2,2-dimethyl-1,3-propanediamine-N,N,N’,N’- tetraacetate (2,2-diMe-1,3-pdta) and of the corresponding magnesium(II), manganese(II), cobalt(II/III), chromium(III) and cadmium(II) complexes has been performed. The structural characterization of the synthesized complexes is also presented, as well as their antifungal and antibacterial activity. Moreover, to define the therapeutic potential of the synthesized complexes, their antiproliferative activity on the healthy human lung fibroblast cell line (MRC-5) has been evaluated. The structural properties and antimicrobial activity of the obtained [M(2,2-diMe-1,3- pdta)]n– complexes have been compared with the corresponding properties of the analogous [M(1,3-pdta)]n– (1,3-propanediamine-N,N,N’,N’-tetraacetate) and [M(1,3-pndta)]n– ((±)-1,3- pentanediamine-N,N,N’,N’-tetraacetate) complexes. In the first part of the doctoral dissertation, the importance of metal complexes with diaminotetracarboxylate ligands is presented and an overview of metal complexes with 1,3- pdta-type ligands that have been synthesized so far and structurally characterized using X-ray structural analysis is given. Procedures for the synthesis of [M(2,2-diMe-1,3-pdta)]n– complexes (M = Mg(II), Mn(II), Cd(II), Co(II/III) and Cr(III)) and methods for their structural characterization and biological evaluation are described in the second part of the dissertation, while in the third part, which refers to the Discussion of the results, the results of the spectroscopic and crystallographic characterization of the synthesized [M(2,2-diMe-1,3- pdta)]n– (M = Mg(II), Mn(II), Cd(II), Co(II/III) and Cr(III)) complexes, as well as the results obtained by evaluation of their antimicrobial activity and toxicity, have been presented

Structural characterization and biological evaluation of polynuclear Mn (II) and Cd(II) complexes with 2,2-dimethyl-1,3-propanediamine-N,N,N ', N '-tetraacetate. The influence of ligand structure and counter cation on the complex nuclearity

New polynuclear manganese(II) and cadmium(II) complexes with 2,2-dimethyl-1,3-propanediamine-N,N, N',N'-tetraacetato ligand (2,2-diMe-1,3-pdta), {Ba[M(2,2-diMe-1,3-pdta)]center dot 3H(2)O}(n) (M = Mn (1) or Cd (2)) were synthesized and characterized by IR spectroscopy and single-crystal X-ray diffraction analysis. In addition, complex 2 was characterized by solution H-1 and C-13 NMR spectroscopy. Crystallographic analysis showed that 2,2-diMe-1,3-pdta ligand is hexadentately coordinated to each M(II) ion through the two nitrogen and four carboxylate oxygen atoms, whereas the one of these oxygen atoms is also involved in coordination to the second M(II) ion of the dinuclear [M-2(2,2-diMe-1,3-pdta)(2)](4-) unit in polymeric structures. Moreover, three of four carboxylic groups of 2,2-diMe-1,3-pdta ligand are additionally bonded to four Ba(II) ions, in three distinctive bridging coordination modes. Each Ba(II) ion is surrounded by ten oxygen atoms, seven belonging to carboxylate groups of 2,2-diMe-1,3-pdta, and three belonging to water molecules. The coordination environment around Mn(II) and Cd(II) ions could be assigned as a face capped octahedron, while coordination polyhedron around Ba(II) ion in these two complexes was described as a distorted sphenocorona. The antimicrobial potential of complexes 1 and 2 and corresponding metal salts used for their synthesis was evaluated against different bacterial and Candida spp. Both complexes showed selective antifungal activity against the tested Candida spp. compared to the bacterial strains, with the minimal inhibitory concentration (MIC) values in the range 3.12 - 12.50 mu M. Moreover, complex 1 caused the slightly decrease of hyphae length, while no significant influence on hyphal length of complex 2 was observed. With aim to assess the therapeutic profile of the complexes, their cytotoxicity was evaluated against the normal human lung fibroblast cell line (MRC-5)

Cobalt(II) and magnesium(II) complexes with 1,3-pdta-type of ligands: influence of an alkyl substituent at 1,3-propanediamine chain on the structural and antimicrobial properties of the complex

To investigate how modification in the structure of 1,3-propanediamine chain of 1,3-pdta (1,3-propanediamine-N,N,N′,N′-tetraacetate) ligand affects the structural and biological properties of the corresponding metal complexes, two new octahedral complexes, [Co(H2O)5Co(2,2-diMe-1,3-pdta)]·H2O (1) and [Mg(H2O)5Mg(2,2-diMe-1,3-pdta)]·1.5H2O (2) (2,2-diMe-1,3-pdta = 2,2-dimethyl-1,3-propanediamine-N,N,N′,N′-tetraacetate), were synthesized and characterized by IR spectroscopy and single-crystal X-ray diffraction analysis. Additionally, UV-Vis and NMR spectroscopic methods were applied for the characterization of 1 and 2, respectively. Crystallographic data indicate that these complexes contain 2,2-diMe-1,3-pdta coordinated to the metal ion through 2 N and 4 O atoms forming [M(H2O)5M′(2,2-diMe-1,3-pdta)] complex unit (M, M′ = Co(II), Co(II) (1) and M, M′ = Mg(II), Mg(II) (2)), which is composed of [M′(2,2-diMe-1,3-pdta)]2− and [M(H2O)5O]2+ octahedra bridged by one of the axial carboxylate groups. The antimicrobial activities of 1 and 2 were evaluated against different bacteria and Candida spp., while their cytotoxic effect was tested on the normal human lung fibroblasts (MRC-5). The ability of 1 and 2 to inhibit formation of C. glabrata biofilms was also assessed. The obtained structural parameters and biological properties of the two complexes were compared to Co(II) and Mg(II) complexes with 1,3-pdta ligand

SINTEZA I SPEKTROSKOPSKA KARAKTERIZACIJA NOVOG RASTVORA U ČVRSTOM STANJU KOJI SADRŽI Mg(II) I Cu(II) KOMPLEKSE SA HEKSADENTATNIM 1,3-PROPANDIAMIN-N,N,N’,N’-TETRAACETATO (1,3-PDTA) LIGANDOM: IN VITRO ANTIFUNGALNA AKTIVNOST 1,3-PDTA-Cu(II) KOMPLEKSA

New solid solution containing Mg(II) and Cu(II) complexes with hexadentate 1,3-propanediamine-N,N,N’,N’-tetraacetate ligand (1,3-pdta), [Mg(H2O)6][Mg0.5Cu0.5(1,3-pdta)].2H2O was synthesized and structurally characterized by elemental microanalyses, molar conductivity and spectroscopic (IR and UV-Vis) measurements. The spectroscopic data of [Mg(H2O)6][Mg0.5Cu0.5(1,3-pdta)].2H2O were compared with those for [Mg(H2O)6][Cu(1,3-pdta)].2H2O  complex of the known molecular structure determined by single-crystal X-ray diffraction analysis (Rychlewska et al., 2000). In vitro growth inhibition activity of [Mg(H2O)6][Mg0.5Cu0.5(1,3-pdta)].2H2O and [Mg(H2O)6][Cu(1,3-pdta)].2H2O against Colletotrichum acutatum and their effects on this fungus sporulation level are investigated. The obtained results showed that the highest percentage of inhibition for mycelium growth was achieved at a concentration of 500 µg/mL for the investigated complexes. The biological activities of the investigated complexes were compared with those for the commercial formulation of fungicide captan (Method 480 SC). Opisana je sinteza i spektroskopska karakterizacija (IR i elektronski apsorpcioni spektri) novog rastvora u čvrstom stanju koji sadrži Mg(II) i Cu(II) komplekse sa 1,3-propandiamin-N,N,N',N'-tetraacetato (1,3-pdta) ligandom, [Mg(H2O)6][Mg0.5Cu0.5(1,3-pdta)].2H2O. Spektroskopski podaci za [Mg(H2O)6][Mg0.5Cu0.5(1,3-pdta)].2H2O kompleks su upoređeni sa odgovarajućim podacima za [Mg(H2O)6][Cu(1,3-pdta)].2H2O kompleks poznate kristalne strukture. Ispitivana je in vitro antimikrobna aktivnost [Mg(H2O)6][Mg0.5Cu0.5(1,3-pdta)].2H2O i [Mg(H2O)6][Cu(1,3-pdta)].2H2O kompleksa prema fitopatogenoj gljivi Colletotrichum acutatum, koja uzrokuje antraknozu. Analiziran je uticaj različitih koncentracija [Mg(H2O)6][Mg0.5Cu0.5(1,3-pdta)].2H2O i [Mg(H2O)6][Cu(1,3-pdta)].2H2O kompleksa na rast micelija i na intenzitet sporulacije gljive. Dobijeni rezultati su pokazali da ovi kompleksi imaju najveću aktivnost pri koncentraciji od 500 µg/mL. Biološka aktivnost [Mg(H2O)6][Mg0.5Cu0.5(1,3-pdta)].2H2O i [Mg(H2O)6][Cu(1,3-pdta)].2H2O je upoređena sa odgovarajućom aktivnošću komercijalnog fungicida 480 SC (Kaptan)

Structural characterization and antimicrobial evaluation of chromium(III) and cobalt(III) complexes with 2,2-diMe-1,3-pdta: Tuning dimensionality of coordination polymer and the water content by alkyl substitution

Hexadentate 2,2-dimethyl-1,3-propanediamine-N,N,N',N'-tetraacetate (2,2-diMe-1,3-pdta) ligand, containing two methyl substituents at the central carbon atom of a 1,3-propanediamine, has been prepared and used for the synthesis of Na[Cr(2,2-diMe-1,3-pdta)].3.75H2O (1) and Na[Co(2,2-diMe-1,3-pdta)].3.88H(2)O (2) complexes. These complexes were characterized by IR and electronic absorption spectroscopy, and single-crystal X-ray diffraction analysis. NMR (H-1 and C-13) spectroscopy was additionally applied for the characterization of complex 2. Crystallographic data indicate that the two investigated crystals are isostructural and contain 2,2-diMe-1,3-pdta ligand coordinated to metal ion through 2N and 4O atoms forming an octahedral complex in which the six-membered 1,3-propanediamine chelate ring adopts a twist-boat conformation. There are four such complex anions in the symmetry independent part of the unit cell. Each complex anion is further connected to the sodium counterion(s) via the bridging carboxylate group(s). Structural changes in 2,2-diMe-1,3-pdta-Cr(III) complex stimulated solely by the presence of alkyl side groups are discussed. The present study shows that in 1,3-pdtatype complexes of Cr(III) and Co(III), the environment at coordination centre can be modified by introducing substitution in one of the carbon atoms of the diamine and the resulting difference in the subunit structure can bring about noticeable change in molecular and crystal structure. The examples illustrate the importance of the steric effect for the fine tuning of the dimensionality of the resulting coordination polymer and the water content. The antimicrobial activity of complexes 1 and 2 was evaluated against different bacterial and Candida spp., while their cytotoxic effects were tested on the normal human lung fibroblast cell line (MRC-5)

Cobalt(III) complexes with (±)-1,3-pentanediamine-<i>N,N,N’,N’</i>-tetraacetate. The influence of nature of alkali and alkaline earth metal counter cations on the supramolecular association of the complex

The coordination of hexadentate (±)-1,3-pentanediamine-N,N,N’,N’-tetraacetate (1,3-pndta) ligand with Co(III) has been investigated. Four octahedral [Co(1,3-pndta)]− complexes containing different counter cations, Li[Co(1,3-pndta)]⋅4H2O (1a), Li[Co(1,3-pndta)]⋅2H2O (1b), K[Co(1,3-pndta)]⋅H2O (1c) and Ca[Co(1,3-pndta)]2⋅5H2O (1d), were synthesized and structurally characterized. Single-crystal X-ray diffraction analysis, IR, NMR (1H and 13C) and electronic absorption spectroscopy were used for characterization of 1a − d. The influence of the ethyl substituent of 1,3-propanediamine chain in 1,3-pndta and the nature of metal counter cation on the structural modalities of carboxylate bridging groups in 1a − d were established by comparing with the analogous [M(1,3-pdta)]n− (1,3-pdta = 1,3-propanediamine-N,N,N’,N’-tetraacetate) and [M(1,3-pndta)]n− complexes (M = Co(III), Cr(III) and Ni(II)). Our studies have shown that the supramolecular association of the complexes is primarily governed by the size of the alkali or alkaline earth metal counter cation and its templating ability, while ethyl substituents, in most cases, prevent the formation of 3D polymeric frameworks.</p