Chromium(III) interactions with nucleotides. II

New derivatives were obtained from Cr(urea)₆Cl₃· 3H₂O in an ethyl acetate medium of chromium(III) with uracil, uridine, 5′UMP, 5′CMP, 5′GMP and 5′IMP. The new derivatives were characterized by elemental analysis, electronic and infrared spectroscopy and thermal analysis. These derivatives proved to be outer sphere complexes, in which the nucleotide, the nucleoside or the base interacts with the starting complex through intramolecular hydrogen bonding.Cr(XMP)(OH)·3H₂O (XMP: 5′UMP, 5′CMP, 5′GMP and 5′IMP) complexes were obtained by hydrolysis of the above derivatives of the nucleotides. In these reactions there is a total substitution of the urea molecules. The derivatives obtained by hydrolysis were characterized in solid state by electronic and infrared spectroscopy. These results provide more insight into the biological role of chromium.     

Some new derivatives of Ni(II) with uracil,uridine and nucleotides

This paper describes the synthesis of compounds of Ni(II) with uracil, uridine and the nucleotides 5′UMP, 5′CMP, 5′GMP and 5′IMP, and their characterization, carried out by elemental analysis, by studying the infrared spectra, diffuse reflectance and conductivity measurement.In the complexes of NiURA (and NiURD) with acetate, direct coordination of the metal ion to the C₄O group of the pyrimidine ring is inferred from the changes observed on the infrared spectrum of the corresponding bands at vCO. The variations in frequency of the vCOO symmetric and asymmetric bands of the acetate group together with the conductivity and reflectance results seem to indicate the dimer structure of the compounds.In the compounds of NiURA (and NiURD) with ethylenediamine indirect bonding of Ni(II)to the pyrimidine ring is inferred, probably established through hydrogen bonds involving the C₄O groups in the base or nucleoside and the −NH₂ groups in the ethylenediamine.In the complexes of Ni-nucleotide, bonding seems to occur through the heterocyclic ring (C₄O for 5′UMP, N(3) for 5′CMP, N(7) for 5′GMP and 5′IMP) together with additional interactions through the phosphate group.     

UV-Vis absorption study of some tetragonal chromium (III) complexes

A UV-Vis absorption study was performed in order to elucidate the electronic energy levels of three tetragonal chromium (III) complexes, namely trans-[Cr(en)₂(CN)₂]ClO₄, trans-[Cr(cyclam)(CN)₂]ClO₄, and trans-[Cr(NH₃)₄(CN)₂]ClO₄. The absorption spectra of the preceding complexes have been analyzed via Gaussian analysis to locate the quartet band maxima of the tetragonal components. The deconvoluted band maxima were then fitted with the tetragonal energy matrices of d³ configuration with full configuration interaction, neglecting spin-orbit interaction. The ligand field parameters D_q, D_t, and D_s along with the electron correlation parameters have been extracted via the fitting procedure. The significance of these parameters and the translated angular overlap model parameters has been discussed. We have also uncovered in the spectrum of the ethylenediamine complex the low intensity doublet absorption bands and a high intensity charge transfer band which have been tentatively assigned.     

Properties of 5′-nucleotidase from nodules of pigeonpea (Cajanus cajan)

5′-Nucleotidase from pigeonpea nodules has been resolved into two forms, N-I and N-II, having M,s of 52 000 and 119 000, respectively. Both forms had pH optima in the acidic range (between pH 5.2 and 5.7) with either CMP, GMP, XMP, IMP or AMP as the substrate. Up to pH 6.6, both forms showed higher activity with CMP followed by GMP, XMP, IMP and AMP, respectively. However, the activity changed with pH in the alkaline range making the enzyme relatively more active with purine nucleotides. Neither of the forms had a requirement for any of the metal ions tested. Fe³⁺ inhibited the enzyme activity; the inhibition at 5, 10 and 15 mM concentrations being 11, 43 and 47%, respectively with N-I and 14,47 and 52%, respectively with N-II. K_m values for AMP, IMP, GMP, CMP and XMP were 0.10, 0.18, 0.40, 0.40 and 0.77 mM, respectively with N-I and 0.12, 0.20, 0.40, 0.40 and 0.99 mM, respectively with N-II. The enzyme was inhibited non-competitively by adenosine and inosine; K_i values being 1.78, 0.25 and 0.30; 3.50, 2.12 and 0.75 mM, respectively with AMP, IMP and XMP as the substrate.     

A Study of the Interaction of Cr(III) Complexes and Their Selective Binding with B-DNA: A Molecular Modeling Approach

Abstract

Molecular modeling and energy minimisation calculations have been used to investigate the interaction of chromium(III) complexes in different ligand environments with various sequences of B-DNA. The complexes are [Cr(salen)(H₂O)₂]⁺; salen denotes 1, 2 bis-salicylideneaminoethane, [Cr(salprn)(H₂O)₂]⁺; salprn denotes 1, 3 bis- salicylideneamino-propane, [Cr(phen)₃]³⁺; phen denotes 1, 10 phenanthroline and [Cr(en)₃]³⁺; en denotes eth- ylenediamine. All the chromium(III) complexes are interacted with the minor groove and major groove of d(AT)₁₂, d(CGCGAATTCGCG)₂ and d(GC)₁₂ sequences of DNA. The binding energy and hydrogen bond parameters of DNA-Cr complex adduct in both the groove have been determined using molecular mechanics approach. The binding energy and formation of hydrogen bonds between chromium(III) complex and DNA has shown that all complexes of chromium(III) prefer minor groove interaction as the favourable binding mode.     

Advances on the interaction of polypyridyl Cr(III) complexes with transporting proteins and its potential relevance in photodynamic therapy

The present study reports a detailed investigation into the interaction of [Cr(phen)₂(dppz)]³⁺ and [Cr(phen)₃]³⁺ with transferrin, the key protein for the transport of Fe³⁺ in blood plasma; its cycle holds promise as an attractive system for strategies of drug targeting to tumor tissues. This can allow us to understand further the role of both complexes as sensitizers in photodynamic therapy (PDT). Chromium(III) complexes, [Cr(phen)₂(dppz)]³⁺ and [Cr(phen)₃]³⁺, (phen = 1,10-phenanthroline and dppz = dipyridophenazine), where dppz is a planar bidentate ligand with an extended π system, have been found to bind strongly with apotransferrin (apoTf) with an intrinsic binding constant, K_b, of (1.8 ± 0.3) × 10⁵ M^− 1 and (1.1 ± 0.1) × 10⁵ M^− 1 at 299 K, for apoTf-[Cr(phen)₂(dppz)]³⁺ and apoTf-[Cr(phen)₃]³⁺, respectively. The interactions of apoTf with the different Cr(III) complexes were assessed employing UV-visible absorption, fluorescence and circular dichroism spectroscopy. The relative fluorescence intensity of the protein decreased when the increasing concentration of Cr(III) complex was added, suggesting that perturbation around the Trp and Tyr residues took place. The analysis of the thermodynamic parameters ΔG, ΔH, ΔS indicated that the presence of the Cr(III) complex stabilizes the protein with a strong entropic contribution. The binding distances and transfer efficiencies for apoTf-[Cr(phen)₂(dppz)]³⁺ and apoTf-[Cr(phen)₃]³⁺ binding reactions were calculated according to Föster theory of non-radiation energy transfer. All these experimental results suggest that [Cr(phen)₂(dppz)]³⁺ and [Cr(phen)₃]³⁺ bind strongly to apoTf indicating that this protein could act as a carrier of these complexes for further applications in PDT.     

Phosphofructokinase of Solanum tuberosum tuber

Potato tuber phosphofructokinase was purified 19·.6-fold by a combination of ethanol fractionation and DEAE-cellulose column chromatography. The enzyme was very unstable; its pH optimum was 8·0. K_m for fructose-6-phosphate, ATP and Mg²⁺ was 2·1 × 10^?4 M, 4·5 × 10^?5 M and 4·0 × 10^?4 M respectively. ITP, GTP, UTP and CTP can act as phosphate donors, but are less active than ATP. Inhibition of enzyme activity by high levels of ATP was reversed by increasing the concentration of fructose-6-phosphate; the affinity of enzyme for fructose-6-phosphate decreased with increasing concentration of ATP. 5′-AMP, 3′,5′-AMP, 3′-AMP, deoxy AMP, UMP, IMP, CMP, GMP, ADP, CDP, GDP and UDP did not reverse the inhibition of enzyme by ATP. ADP, phosphoenolpyruvate and citrate inhibited phosphofructokinase activity but Pi did not affect it. Phosphofructokinase was not reactivated reversibly by mild change of pH and addition of effectors.     

Interaction of Purine Nucleotides with Cobalt-Hexammine,Cobalt-Pentammine and Cobalt- Tetrammine Cations. Evidence for the Rigidity of Adenosine and Flexibility of Guanosine and Deoxyguanosine Sugar Conformations

Abstract

The interaction of adenosine-5′-monophosphate (5′-AMP), guanosine-5′-monophosphate (5′-GMP) and 2′-deoxyguanosine-5′-monophosphate (5′-dGMP) with the [Co(NH₃)₆]³⁺, [CO(NH₃)₅C1]²⁺ and [CO(NH₃)₄C1₂]⁺ cations has been investigated in aqueous solution with metal/nucleotide ratios (r) of 1/2, 1 and 2 at neutral pH. The solid complexes have been isolated and characterized by FT-IR and ¹H-NMR spectroscopy.

The complexes are polymeric in nature both in the crystalline solid and aqueous solution. The binding of the cobalt-hexammine cation is indirectly (via NH₃) through the N-7 and the PO₃ ^2- groups of the AMP and via O-6, N-7 and the PO₃ ^2- of the GMP and dGMP anions (outer-sphere). The cobalt-pentammine and cobalt-tetrammine bindings are through the phosphate groups (inner-sphere) and the N-7 site (outer-sphere) of these nucleotide anions. The ribose moiety shows C2′-endo/anti conformation, in the free AMP and GMP anions as well as in the cobalt-ammine - AMP complexes, whereas a mixture of the C2′-endo/anti and C3′-endo/anti sugar puckers were observed for the Co(NH₃)₆-GMP, Co(NH₃)₅-GMP and a C3′-endo/anti conformer for the Co(NH₃)₄-GMP complexes. The deoxyribose showed an O4′-endo/anti conformation for the free dGMP anion and a C3′-endo/anti for the Co(NH₃)₆-dGMP, Co(NH₃)₅-dGMP and Co(NH₃)₄-dGMP complexes.     

Synthesis and P2Y receptor activity of nucleoside 5′-phosphonate derivatives

Ribose-based nucleoside 5′-diphosphates and triphosphates and related nucleotides were compared in their potency at the P2Y receptors with the corresponding nucleoside 5′-phosphonate derivatives. Phosphonate derivatives of UTP and ATP activated the P2Y₂ receptor but were inactive or weakly active at P2Y₄ receptor. Uridine 5′-(diphospho)phosphonate was approximately as potent at the P2Y₂ receptor as at the UDP-activated P2Y₆ receptor. These results suggest that removal of the 5′-oxygen atom from nucleotide agonist derivatives reduces but does not prevent interaction with the P2Y₂ receptor. Uridine 5′-(phospho)phosphonate as well as the 5′-methylenephosphonate equivalent of UMP were inactive at the P2Y₄ receptor and exhibited maximal effects at the P2Y₂ receptor that were ?50% of that of UTP suggesting novel action of these analogues.     

Inhibition of 5′-nucleotidase from Ehrlich ascites-tumour cells by nucleoside triphosphates

1. 5'-Nucleotidase activity was obtained in a soluble form after treatment of a particulate fraction from Ehrlich ascites-tumour cells with deoxycholate. The relative rates of hydrolysis of 6-thioinosine 5'-phosphate, UMP, AMP, CMP, GMP, IMP, xanthosine monophosphate, thymidine monophosphate and 2',3'-AMP were 180, 129, 100, 93, 83, 79, 46, 41 and 3 respectively. 2. Values found for the Michaelis constant were: AMP, 67+/-12mum; IMP, 111+/-8mum; GMP, 93mum. 3. ATP and thymidine triphosphate were competitive inhibitors of AMP hydrolysis (inhibitor constants 0.4 and 4.8mum respectively); UTP, GTP and CTP were mixed competitive and non-competitive inhibitors. Thymidine triphosphate was a competitive inhibitor of IMP hydrolysis (inhibitor constant 14.4mum) and ATP, UTP and GTP showed mixed competitive and non-competitive inhibition. 4. ATP, thymidine triphosphate, UTP, GTP and CTP did not completely inhibit hydrolysis of AMP, IMP and UMP; the concentrations of ATP required to inhibit AMP and IMP hydrolysis by 50% were 12 and 230mum respectively. 5. Non-hyperbolic curves relating activity to UMP concentration were obtained in the presence and absence of triphosphates. 6. After fractionation on Sephadex G-200 columns a single peak of 5'-nucleotidase activity (particle weight 120000-125000) was obtained with AMP, IMP and GMP as substrates. UMP hydrolysis was catalysed by enzyme in this peak and in two slower peaks corresponding to apparent particle weights of 32000 and 16000; a single component (particle weight 120000), reacting with UMP and insensitive to UTP inhibition, was obtained when the column was eluted with buffer containing 1mm-UMP. 7. The possible significance of the results in the regulation of tumour-cell 5'-nucleotidase is discussed.     

New complexes of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III) and Gd(III) ions with morin

New solid complex compounds of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III) and Gd(III) ions with morin were synthesized. The molecular formula of the complexes is Ln(C₁₅H₉O₇)₃ · nH₂O, where Ln is the cation of lanthanide and n = 6 for La(III), Sm(III), Gd(III) or n = 8 for Ce(III), Pr(III), Nd(III) and Eu(III). Thermogravimetric studies and the values of dehydration enthalpy indicate that water occurring in the compounds is not present in the inner coordination sphere of the complex. The structure of the complexes was determined on the basis of UV-visible, IR, MS, ¹H NMR and ¹³C NMR analyses. It was found that in binding the lanthanide ions the following groups of morin take part: 3OH and 4CO in the case of complexes of La, Pr, Nd, Sm and Eu, or 5OH and 4CO in the case of complexes of Ce and Gd. The complexes are five- and six-membered chelate compounds.     

The interactions of cis- and trans-diammineplatinum compounds with 5′-guanosine monophosphate and 5′-deoxyguanosine monophosphate. A proton nmr investigation

The interactions of cis- and trans-diammineplatinum compounds with 5′-GMP and 5′-dGMP in dilute aqueous solution at neutral pH were investigated by ¹H nmr. In addition to the 1:2 Pt nucleotide complexes cis- and trans-Pt(NH₃)₂(GMP)₂, it was possible to study the formation of the 1:1 Pt-nucleotide complexes with either one coordinated water or chloride ion. At 5°C GMP reacts with a stoichiometric amount of cis-diaquodiammine-platinum to yield cis-Pt(NH₃)₂(GMP) (H₂O) as a sole reaction product. From the present results it is concluded that such a complex may play an important role as the initial reaction product between antitumor compounds like cis-Pt(NH₃)₂Cl₂ and guanine in DNA in living organisms. The coupling constant ³J(H(1′)-H(2′)) of the H(1′) sugar proton in cis-Pt(NH₃)₂(GMP)₂ is temperature dependent, indicating a conformational change in the sugar moiety.     

The high-energy intraconfigurational spin-forbidden bands in the spectra of quadrate chromium(III) complexes

The high-energy intraconfigurational spin-forbidden bands expected in the region of 20 000 cm⁻¹ have been uncovered in the spectra of a number of trans-diacidobis(ethylenediamine) chromium(III)complexes. These bands have been fitted to the quadrate components of the cubic transition ⁴A_2g → ²T_2g including spin-orbit interaction. Two interconfigurational spin-forbidden bands in the spectrum of trans-[Cr(en)₂(dmf)₂](ClO₄)₃ have been uncovered and interpretted.     

Polymer–cobalt(III) complexes: structural analysis of metal chelates on DNA interaction and comparative cytotoxic activity

A new series of pendant-type polymer-cobalt(III) complexes, [Co(LL)₂(BPEI)Cl]²⁺, (where BPEI?=?branched polyethyleneimine, LL?=?dipyrido[3,2-a:2′,3′-c](6,7,8,9-tetrahydro)phenazine (dpqc), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq) and imidazo[4,5-f]1,10-phenanthroline (ip)) each with three different degrees of coordination have been synthesized and characterized. Studies to know the mode and strength of interaction between these polymer–metal complexes and calf thymus DNA have been performed by UV–Visible absorption and emission techniques. Among these series, each polymer metal complex having higher binding strength with DNA has been selected to test against human cancer/normal cell lines. On the basis of these spectral studies, it is proposed that our polymer–metal complexes bind with DNA mainly through intercalation along with some electrostatic binding. The order of binding strength for the complexes with ligand, dpqc?>?dpq?>?ip. The analysis of the results suggests that polymer–cobalt(III) complexes with higher degree of coordination effectively binds with DNA due to the presence of large number of positively charged cobalt(III) chelates in the polymer chain which cooperatively act to increase the overall binding strength. These polymer–cobalt(III) complexes with hydrophobic ligands around the cobalt(III) metal centre favour the base stacking interactions via intercalation. All the complexes show very good anticancer activities and increasing of binding strength results in higher inhibition value. The polymer–cobalt(III) complex with dpqc ligand possess two fold increased anticancer activity when compared to complexes with other ligands against MCF-7 cells. Besides, the complexes were insensitive towards the growth of normal cells (HEK-293) at the IC₅₀ concentration.     

Entamoeba histolytica: Nucleic acid precursors affecting axenic growth

Treatment of Panmede and Trypticase, in water, with activated carbon and subsequently combining the filtered solution with glucose, cysteine, salts, serum and vitamins results in a medium depleted in the nucleic acid precursors required to sustain a high level of growth of axenic Entamoeba histolytica. Additions to the depleted medium which stimulated sustained growth, were the following, in the order of increasing efficacy: adenosine, adenine, AMP, AMP + GMP, AMP + GMP + UMP + CMP, or yeast ribonucleic acid. The last three additions restored growth to the level of cultures in TP-S-1 medium. No stimulation of sustained growth was found with GMP, IMP, UMP, or CMP, singly.     

Synergistic Taste Effects of Some New Ribonucleotide Derivatives

Taste effects of six newly synthesized ribonucleotide derivatives, i.e., disodium salts of 2-methyl-5′-inosinic acid · 6H₂O, 2-ethyl-5′-inosinic acid · 1.5H₂O, 2-N-methyl-5′-guanylic acid · 5.5H₂O, 2-N-dimethyl-5′-guanylic acid · 2.5H₂O, 2-methylthio-5′-inosinic acid · 6H₂O and 2-ethylthio-5′-inosinic acid · 2H₂O, were studied. Stimulus thresholds (detection thresholds) of these derivatives ranged from about 0.02 to 0.006 g/100ml. Flavor-enhancing activities of them were 2.3 to 8.0 times larger than that of disodium 5′-inosinate · 7.5H₂O IMP) in the synergistic effect with monosodium glutamate. Furthermore, the quality of taste of all the derivatives was recognized to be the same kind to that of IMP.     

Interaction of [RuCl2(PR3)3] (R = Ph, p-tolyl) with some Rh(III), Ir(III) and Pt(IV) tertiary phosphine complexes

Reactions of RuCl₂(PR₃)₃ [PR₃ = PPh₃ or P(p-tolyl)₃ with several monomeric phosphine complexes of rhodium(III), iridium(III) and platinum(IV) have been studied. The reactions with mer-MCl₃(P′R₃)₃ (M = Rh, P′R₃ = PEt₂Ph, PMe₂Ph, PMe₂Ph; M = Ir, P′R₃ = PBuPh₂, PMePh₂, PEt₂Ph) involves a phosphine ligand transfer between metal atoms to afford novel dark coloured heterobimetallic complexes containing a triple chloro-bridge. The reactions of RuCl₂(PR₃)₃ with PtCl₄(P′R₃)₂ (P′R₃ = PEt₂Ph, PBu₂Ph), however, do not give evidence for the formation of dinuclear complexes containing the (RuCl₃Pt) unit, but a reduction of Pt^IV to Pt^II occurs with transfer of phosphine ligands between the two metals. The formulation of these complexes has been established by ³¹P NMR spectroscopy.     

Nature and composition of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Gd(III), Dy(III) and Ho(III) complexes of embelin

The isolation and characterization of nine polymeric complexes of the general formula [M(L)_1.5S₂]_n (where M is the metal ion, L the ligand and S the solvent, C₂H₅OH) of La(III) and Ce(III), Pr(III), Nd(III), Sm(III), Gd(III), Tb(III), Dy(III), Ho(III) with.the biologically active compound embelin using elemental and thermal analysis, infrared and electronic spectral studies is reported.     

Isotope effect on the nonradiative decay in mixed amminechromium(III) complexes

Mixed amminechromium(III) complexes of the general formula [Cr(NH₃)_6−nX_n]^m (X = H₂O, SCN⁻) have been prepared and deuterated in the presence of a base. Phosphorescence decay times have been measured at ca. 77 K and the isotope effect on the nonradiative deactivation is discussed using Kupka's theory.     

The interaction of the ruthenium(III)-chloride system with DNA

The interaction of RuCl₃ in aqueous solution with DNA has been studied at various r values. Electronic spectra, melting curves and sedimentation experiments indicate that Ru(III) is bound mainly to the phosphate moieties of DNA, causing stabilization of the double helix. For small values of r we observe renaturation upon cooling and possible interstrand cross-linking that persists at room temperature. During the second heating the melting temperature decreases, indicating substantial interaction of Ru(III) with the bases of the DNA. Ru(III) interacts with the nitrogen of the bases only when DNA is almost denaturated, and this cross-linking interaction seems to be quite strong.