Papers by Ilpo Mutikainen
European Journal of Inorganic Chemistry, 2002
The syntheses and properties of two novel [Ru(bpy) 2 (L−LЈ)] n+ complexes with L−LЈ = 3-carboxy-5... more The syntheses and properties of two novel [Ru(bpy) 2 (L−LЈ)] n+ complexes with L−LЈ = 3-carboxy-5-(pyrid-2Ј-yl)-1,2,4triazole (H 2 cpt) or 3-(ethoxycarbonyl)-5-(pyrid-2Ј-yl)-1,2,4triazole (Hcept) ligands are described. Previous publications on Ru II complexes containing (pyrid-2Ј-yl)-1,2,4-triazoles revealed that their coordination is possible via N1 and N4 of the triazole ring. 1 H NMR spectroscopic data and the crystal structure of [Ru(bpy) 2 (cept)]PF 6 ·H 2 O (2) indicate that the coordination of the Hcpt − and cept − occurs via N1 of the triazole ring. The crystals of 2 are monoclinic and belong to the space group P2 1 /n with a = 12.339(7), b = 16.512 , c = 16.802(8) Å , β = 110.29(4)°, and Z = 4. A water molecule is hydrogen-bonded to the carbonyl oxygen atom of the [ ‡] Current address:
Biochemical and chemical characterization of trifluoromethylglyoxal bis(guanylhydrazone), a close analog of the antileukemic drug mitoguazone
Zeitschrift fur Naturforschung C
In order to study the structure-activity relationships of bis(guanylhydrazone) type polyamine ant... more In order to study the structure-activity relationships of bis(guanylhydrazone) type polyamine antimetabolites, trifluoromethylglyoxal bis(guanylhydrazone) (CF3-GBG), a close analog of the antileukemic drug methylglyoxal bis(guanylhydrazone) (mitoguazone, MGBG) was synthesized according to a novel modification of previous methods, yielding single crystals. Single-crystal X-ray crystallography revealed the presence of an isomer different from the one detected in the case of MGBG and all other bis(guanylhydrazones) so far studied. In contrast to MGBG, CF3-GBG was shown to be a very weak inhibitor of yeast adenosylmethionine decarboxylase, being thus devoid of value as a polyamine antimetabolite. In addition, the compound did not have antiproliferative activity against mouse L1210 leukemia cells in vitro. As long as analogous isomers of the two compounds are not available, no conclusions can be drawn about the reasons lying behind the drastical differences between their biological properties.
Biochemical characterization of propylglyoxal bis(guanylhydrazone). Facile synthesis of monoalkylglyoxal bis(guanylhydrazones)
Zeitschrift fur Naturforschung. C, Journal of biosciences
Propylglyoxal bis(guanylhydrazone) sulfate, a novel analog of the well-known antileukemic drug me... more Propylglyoxal bis(guanylhydrazone) sulfate, a novel analog of the well-known antileukemic drug methylglyoxal bis(guanylhydrazone), has been prepared from 2,2-dibromopentanal, and the compound has been characterized biochemically. Although it is a powerful inhibitor of S-adenosylmethionine decarboxylase, its Ki value (0.2 microM) is considerably higher than that of ethylglyoxal bis(guanylhydrazone) (0.06 microM). The compound is only poorly taken up by tumor cells, and its accumulation is not stimulated by a prior exposure of the tumor cells to difluoromethylornithine, a compound that causes polyamine depletion. Thus, the uptake characteristics of the compound are similar to those of ethylglyoxal bis(guanylhydrazone), but in striking contrast to those of methylglyoxal and glyoxal bis(guanylhydrazones). Since the configuration of the double bonds in glyoxal, methylglyoxal and propylglyoxal bis(guanylhydrazones) has been shown to be identical, the different uptake characteristics are probably only due to differences in side chain size and/or hydrophobicity.
Biochemical properties and crystal structure of ethylmethylglyoxal bis(guanylhydrazone) sulfate--an extremely powerful novel inhibitor of adenosylmethionine decarboxylase
Zeitschrift fur Naturforschung C
Ethylmethylglyoxal bis(guanylhydrazone) (EMGBG) sulfate, an analog of the well-known anti-leukemi... more Ethylmethylglyoxal bis(guanylhydrazone) (EMGBG) sulfate, an analog of the well-known anti-leukemic drug methylglyoxal bis(guanylhydrazone), was synthesized. It was shown to be an extremely powerful competitive inhibitor of eukaryotic S-adenosylmethionine decarboxylase, with an apparent Ki value 12 nM. Thus, it appears to be the most powerful known inhibitor of the enzyme, being almost an order of magnitude more powerful than the corresponding ethylglyoxal derivative. It neither inhibited the proliferation of mouse L1210 leukemia cells in vitro, nor did it potentiate the growth inhibition produced by alpha-difluoromethyl ornithine. In this respect, its properties are closely related to those of dimethylglyoxal, ethylglyoxal and propylglyoxal bis(guanylhydrazones), while in striking contrast to those of the antiproliferative glyoxal and methylglyoxal analogs. EMGBG also inhibited intestinal diamine oxidase activity (Ki 0.7 microM). EMGBG sulfate was crystallized from water, giving orthorhombic crystals (space group Pbcn). Their crystal and molecular structure was determined by X-ray diffraction methods. The carbon-nitrogen double bonds between the ethylmethylglyoxal part and the aminoguanidine moieties were found to have the same configuration as they are known to have in the salts of glyoxal, methylglyoxal and propylglyoxal bis(guanylhydrazones). The glyoxal bis(guanylhydrazone) chain of the EMGBG cation deviated strongly from planarity, thus differing dramatically from the corresponding chains of the glyoxal, methylglyoxal and propylglyoxal analogs.
{2,2′-[(R,R)-Cyclohexane-1,2-diylbis(nitrilomethylidyne)]bis[6-tert-butyl-4-(triphenylphosphoniomethyl)phenolato]-O,N,N′,O′}copper(II) dichloride hexakis(deuterochloroform) solvate
Acta Crystallographica Section C Crystal Structure Communications
ABSTRACT
Biochemical and chemical characterization of phenylglyoxal bis(guanylhydrazone), an aromatic analogue of mitoguazone
Anti-cancer drug design
Since little has been known about the properties of aromatic analogues of the antineoplastic agen... more Since little has been known about the properties of aromatic analogues of the antineoplastic agent methylglyoxal bis(guanylhydrazone) (MGBG), an investigation was performed on phenylglyoxal bis(guanylhydrazone) (PhGBG). PhGBG competitively inhibited yeast adenosylmethionine decarboxylase (AdoMetDC) with a Ki of 65 microM. As compared to MGBG (Ki 0.23 microM), PhGBG is a much weaker inhibitor, being even weaker than the unsubstituted congener glyoxal bis(guanylhydrazone) (GBG, Ki 18 microM). PhGBG inhibited porcine kidney diamine oxidase (DAO) non-competitively, being a more potent inhibitor (Ki 0.12 microM) than GBG (Ki 0.17 microM) or MGBG (Ki 0.33 microM). Thus, PhGBG has an unfavourably high ratio of Ki(AdoMetDC)/Ki(DAO) for potential use for selectively inhibiting polyamine biosynthesis. This does not exclude the possibility that PhGBG or other aromatic congeners might have therapeutic value since the corresponding ratio of the antileukaemic congeners GBG and MGBG is also high a...
http://onlinelibrary.wiley.com/doi/10.1002/1099-0682%28200207%292002:7%3C1765::AID-EJIC1765%3E3.0.CO;2-%23/abstract
European Journal of Inorganic Chemistry
he syntheses and properties of two novel [Ru(bpy)2(L−L′)]n+ complexes with L−L′ = 3-carboxy-5-(py... more he syntheses and properties of two novel [Ru(bpy)2(L−L′)]n+ complexes with L−L′ = 3-carboxy-5-(pyrid-2′-yl)-1,2,4triazole (H2cpt) or 3-(ethoxycarbonyl)-5-(pyrid-2′-yl)-1,2,4-triazole (Hcept) ligands are described. Previous publications on RuII complexes containing (pyrid-2′-yl)-1,2,4-triazoles revealed that their coordination is possible via N1 and N4 of the triazole ring. 1H NMR spectroscopic data and the crystal structure of [Ru(bpy)2(cept)]PF6·H2O (2) indicate that the coordination of the Hcpt− and cept− occurs via N1 of the triazole ring. The crystals of 2 are monoclinic and belong to the space group P21/n with a = 12.339(7), b = 16.512(7), c = 16.802(8) Å, β = 110.29(4)°, and Z = 4. A water molecule is hydrogen-bonded to the carbonyl oxygen atom of the ethoxycarbonyl group with an O···O distance of 2.891 Å. Spectroscopic measurements reveal that H2cpt and Hcept are strong σ-donor ligands. When coordinated to a ruthenium(II) centre, both triazole ligands reported in this study l...
Ethylmethylglyoxal Bis(amidinohydrazonium) Dichloride–Water (1/2)
Acta Crystallographica Section C Crystal Structure Communications
The title compound, C7H18N82+.2Cl(-).2H(2)O, has been found to exist as the anti-anti isomer, wit... more The title compound, C7H18N82+.2Cl(-).2H(2)O, has been found to exist as the anti-anti isomer, with an all-trans configuration the bis(amidinohydrazone) chain, just like glyoxal bis(amidinohydrazone) and all its mono- and dialkylglyoxal analogues studied so far. The bis-(amidinohydrazone) backbone of the dication is planar in contrast to the corresponding sulfate salt.
The crystal and molecular structure of aminoguanidine hemioxalate, a salt in which aminoguanidine... more The crystal and molecular structure of aminoguanidine hemioxalate, a salt in which aminoguanidine exists in the monocation form, was determined by single crystal X-ray diffraction. The salt crystallizes in the monoclinic space group P2(1)/n with unit cell dimensions ofa=4.95,b=10.46,c=10.40 Å, ß=92.57°, andZ=4. The structure contains one oxalate ion for every two CN4H7+ ions, the latter being practically planar. The structure
Synthesis, spectroscopy, crystal structure and magnetism of tetrakis(2-aminopyrimidine)bis(μ-methoxo)bis(perchlorato)dicopper(II): a rare case of distortion isomerism
Polyhedron, 2004
The dinuclear compound [Cu(ampym)2(μ-CH3O)(ClO4)]2 (ampym=2-aminopyrimidine) has been synthesized... more The dinuclear compound [Cu(ampym)2(μ-CH3O)(ClO4)]2 (ampym=2-aminopyrimidine) has been synthesized and characterized by X-ray crystallography and infrared spectroscopy. In addition, EPR and magnetic measurements have been performed and related to the dinuclear structural details.The compound crystallizes in the monoclinic space group P21/c, with a=8.0190(13), b=18.2500(11), c=10.955(2) Å, β=116.390(13)°, V=1436.2(4) Å3 and Z=2. The coordination geometry around the Cu(II) ion is distorted square
Synthesis and characterization of bulky salen-type complexes of Co, Cu, Fe, Mn and Ni with amphiphilic solubility properties
Journal of the Chemical Society, Dalton Transactions, 2001
ABSTRACT Several new bulky salen-type Schiff base ligands and their complexes with first-row tran... more ABSTRACT Several new bulky salen-type Schiff base ligands and their complexes with first-row transition metals Co, Cu, Fe, Mn and Ni have been synthesized and characterized. The ligands contain tert-butyl and methyl(triphenylphosphonium chloride) substituents in aromatic rings providing flexible solubility properties. Crystal structures of some of the complexes were determined.
Crystal and molecular structure of glyoxal bis(amidinohydrazone) dihydrochloride; biochemical aspects
Journal of the Chemical Society, Perkin Transactions 2, 1986
ABSTRACT The crystal and molecular structure of the title compound has been determined by single-... more ABSTRACT The crystal and molecular structure of the title compound has been determined by single-crystal X-ray analysis and refined to an R value of 0.027. The crystal is monoclinic, space group P21/c with a= 5.476(3), b= 14.540(7), c= 6.915(3)Å, β= 99.88(4)°, and Z= 2. The structure consists of layers of dipositive cations [C4H12N8]2+ and Cl– ions. The planar cation has the trans-configuration of the chain. Hydrogen bonds of the type N–H Cl– are formed within the layers, but not between them. The molecules in the crystal are held together through stacking and via the delocalized π-electron system. The mean planes of the cations are approximately 3.51 Å apart. The crystal structure is compared with that of other bis(amidinohydrazone) derivatives and the relationship between crystal structure and biochemical properties is discussed.
Low-Temperature Crystal Structures and Thermal Decomposition of Uranyl Hydrogen Selenite Monohydrate, UO2(HSeO3)2.H2O and Diammonium Uranyl Selenite Hemihydrate, (NH4)2UO2(SeO3)2.0.5H2O
Acta Chemica Scandinavica, 1997
Complex Formation Equilibria of Some Aliphatic alpha-Hydroxycarboxylic Acids. 2. The Study of Copper(II) Complexes
Acta Chemica Scandinavica, 1995
A unique chain of trinuclear Cu(II) units containing both neutral and anionic N-(pyrimidin-2-yl) acetamide (Haapm, resp. aapm) as a ligand and dicyanamide (dca): Synthesis, characterization, X-ray structure and magnetism of [Cu3(μ-aapm)2(μ-dca)2(Haapm)2](CF3SO3)2
Polyhedron, 2008
The synthesis, crystal structure, as well as the electronic and magnetic properties, of a new tri... more The synthesis, crystal structure, as well as the electronic and magnetic properties, of a new trinuclear-based Cu(II) compound [Cu3(μ-aapm)2(μ-dca)2(Haapm)2](CF3SO3)2, containing the ligands N-(pyridin-2yl)acetamide (Haapm) and dicyanamide (dca) is reported.The central Cu1 atom has a distorted elongated octahedral coordination with the basal plane comprised of two nitrogens from two different tetrachelating dehydronated aapm ligands and two nitrogen atoms of two dca anions (Cu–N distances 2.016(2) and 1.988(3)Å). The apical positions are occupied by two nitrogen atoms of the two different tetrachelating aapm ligands (Cu–N distance 2.539(3)Å), with a trans angle of 180°. Also the N–Cu–N angle is extremely small (58.25(9)°), due to the four-membered chelate ring. The outer Cu2 ions have also a distorted octahedral geometry with the basal plane formed of two nitrogens and two oxygen atoms from a tetrachelating dehydronated aapm ligand (which is bridging between Cu1 and Cu2) and from a Haapm ligand (Cu–N/O distances vary from 1.95.4(2) and 2.022(2)Å), with basal angles of 177.29(9)° and 171.12(8)°. The apical positions are occupied by an oxygen atom of a triflate anion (Cu–O distance 2.534(3)Å) and a nitrogen atom of a neighbouring dca anion (Cu–N distance 2.314(3)Å), with an angle of 171.92(8)°. The Cu–Cu distance within the trinuclear unit is 5.23Å. The dca anions are connected in an end-to-end fashion to a neighbouring Cu(II) ion (Cu–Cu distance 8.54Å), forming in this way a chain of trinuclear units bridged by two dca anions.The EPR as a powdered solid revealed a weak S=1 triplet spectrum at RT. The magnetic susceptibility measurements, measured from 5 to 200K, revealed a weak ferromagnetic interaction between the Cu(II) ions.
Experimental and Computational Studies on Aminoguanidine Free Base, Monocation and Dication, Part I: The Crystal and Molecular Structure of Aminoguanidine Monohydrochloride and the ab Initio Structure of the Endiamine Tautomer of Aminoguanidine Free Base
Zeitschrift für Naturforschung B, 1996
ABSTRACT The crystal and molecular structure of aminoguanidine monohydrochloride, CN4H7+.Cl-, in ... more ABSTRACT The crystal and molecular structure of aminoguanidine monohydrochloride, CN4H7+.Cl-, in which aminonoguanidine exists in the monocation form, was determined by single-crystal X-ray diffraction. The structure of the monocation is largely similar to that of aminoguanidine dication as present in previously studied divalent salts. The monocation was found to exist in the form of the tautomer that allows strong resonance in the guanyl group. As compared to the dication, the terminal hydrazine nitrogen atom bears one hydrogen atom less. The monocation is planar, the only atoms deviating from the plane being the hydrogens attached to the terminal hydrazine nitrogen. Quantum chemical calculations on the endiamine tautomer of aminoguanidine free base as well as on aminoguanidine monocation and dication were also performed by using the HF and MP2 ab initio methods and also the B3-LYP and B-LYP methods based on density functional theory. On the basis of the calculations, a predicted structure of the endiamine tautomer of aminoguanidine free base is presented.
Crystal and Molecular Structure of Aminoguanidine Sulphate, an Important Enzyme Inhibitor and Starting Material of Drug Syntheses
Zeitschrift für Naturforschung B, 1994
ABSTRACT Aminoguanidine is not only an agent with a variety of pharmacological effects but also a... more ABSTRACT Aminoguanidine is not only an agent with a variety of pharmacological effects but also an important starting material of am idinohydrazone-type drugs and enzyme inhibitors. There fore, we have now synthesized am inoguanidine sulphate CN
Structure of propylglyoxal bis(amidinohydrazone) sulfate dihydrate
Crystal and Molecular Structures of the Free Base and the Monohydrochloride Salt of the Antileukemic Agent Glyoxal bis(Amidinohydrazone) [`Glyoxal bis(Guanylhydrazone)’]
Zeitschrift für Naturforschung B, 1993
ABSTRACT The first study on the crystal and molecular structures of basic forms of bis(amidinohyd... more ABSTRACT The first study on the crystal and molecular structures of basic forms of bis(amidinohydrazones) is reported. The structures of the free base and the monohydrochloride salt of the antileukemic agent glyoxal bis(amidinohydrazone) (GBG) were determined by single crystal X-ray diffraction and were refined to R-values of 0.038 and 0.040, respectively. These structures are of special interest because recent results indicate that, in contrast to previous assumptions, the free base may be the actual antileukemic form of bis(amidinohydrazones) and that the monocation form is the predominant species of antileukemic bis(amidinohydrazones) at physiological conditions. In the crystals of the free base as well as in those of the monohydrochloride salt, GBG was found to exist solely in the all-trans configuration of the chain and to consist of one of the three possible geometrical isomers only. In the solid state, GBG free base consists solely of the endiamine tautomer instead of the 'classical’ carboximidamide tautomer, as does also the non-protonated part of GBG monocation in the monohydrochloride salt. Proton NMR measurements indicated that the free base consists of the endiamine tautomer also in dimethyl sulfoxide solution. In the solid state, both of the compounds studied consist of stacks of planes. In the case of the free base, the stacks are crisscross to each other. The distance between the mean planes of the molecules or the monocations is approximately 3.5 Å. The crystals of the monohydrochloride salt contain one molecule of water per each GBG monocation. In both compounds studied, the molecules in the crystals are held together by very extensive hydrogen bond networks and by the interaction of delocalized π-electrons. The crystal of C
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Papers by Ilpo Mutikainen