Unique cooperative binding interaction observed between a minor groove binding Pt antitumor agent and Hoechst dye 33258

The trinuclear compound [{Pt(NH3)3}2mu-{trans-Pt(NH3)2(H2N(CH2)6NH2)}2(6+) (0,0,0/t,t,t) binds to DNA only through noncovalent hydrogen bonding and electrostatic interactions. The presence of this 6+ cation allows discrimination of binding modes for common DNA ligands: binding of minor-groove agents such as Hoechst 33258 is cooperative, and dye-DNA interaction is enhanced whereas intercalation as exemplified by ethidium bromide is competitively inhibited.     

Mechanism of two-electron oxidation of deoxyguanosine 5'-monophosphate by a platinum(IV) complex

Many transition metal complexes mediate DNA oxidation in the presence of oxidizing radiation, photosensitizers, or oxidants. The final DNA oxidation products vary depending on the nature of metal complexes and the structure of DNA. Here we propose a mechanism of oxidation of a nucleotide, deoxyguanosine 5'-monophosphate (dGMP) by trans-d,l-1,2-diaminocyclohexanetetrachloroplatinum (trans-Pt(d,l)(1,2-(NH(2))(2)C(6)H(10))Cl(4), [Pt(IV)Cl(4)(dach)]; dach = diaminocyclohexane) to produce 7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-monophosphate (8-oxo-dGMP) stoichiometrically. The reaction was studied by high-performance liquid chromatography (HPLC), (1)H and (31)P nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). The proposed mechanism involves Pt(IV) binding to N7 of dGMP followed by cyclization via nucleophilic attack of a phosphate oxygen at C8 of dGMP. The next step is an inner-sphere, two-electron transfer to produce a cyclic phosphodiester intermediate, 8-hydroxyguanosine cyclic 5',8-(hydrogen phosphate). This intermediate slowly converts to 8-oxo-dGMP by reacting with solvent H(2)O.     

Synthesis, characterisation and speciation studies of heterobimetallic pyridinehydroxamate-bridged Pt(II)/M(II) complexes (M = Cu, Ni, Zn). Crystal structure of a novel heterobimetallic 3-pyridinehydroxamate-bridged Pt(II)/Cu(II) wave-like coordination polymer

The reaction of cis-[Pt(NH3)2(3-pyhaH)2]2+ (3-pyhaH = 3-pyridinehydroxamic acid) and cis-[Pt(NH3)2(4-pyhaH)2]2+ (4-pyhaH = 4-pyridinehydroxamic acid) with Cu(II), Ni(II) or Zn(II) in aqueous solution affords novel heterobimetallic pyridinehydroxamate-bridged complexes, {cis-[Pt(NH3)2(mu-3-pyha)M(mu-3-pyha)].SO4.xH2O}n and {cis-[Pt(NH3)2(mu-4-pyha)M(mu-4-pyha)].SO4.xH2O}n respectively. The crystal and molecular structure of one of these, {cis-[Pt(NH3)2(mu-3-pyha)Cu(mu-3-pyha)]SO4.8H2O}n 3a, has been determined and was found to be a novel heterobimetallic wave-like coordination polymer, the structure of which contains interlinked pyridinehydroxamate-bridged repeating units of Pt(II) and Cu(II) ions in slightly distorted square-planar N4 and O4 coordination environments respectively and extensive hydrogen-bonding through the Pt ammines and the deprotonated hydroxamate O and via the O of the SO4(2-) counterions and the H(N) of the hydroxamate moiety. Spectrophotometric and speciation studies on the other heterobimetallic systems confirm that very similar species are being formed in solution and based on elemental analysis and spectroscopic results analogous complexes are formed in the solid-state. In this paper, we report the first examples of coordination polymers incorporating both Pt(II)/Cu(II), Pt(II)/Ni(II) and Pt(II)/Zn(II) and containing pyridinehydroxamic acids as bridging scaffolds.     

The Uracil C(5) Position as a Metal Binding Site: Solution and X-ray Crystal Structure Studies of Pt(II) and Hg(II) Compounds

1,3-Dimethyluracil (1,3-DimeU) reacts with trans-[(CH(3)NH(2))(2)Pt(H(2)O)(2)](+) to give trans-[(CH(3)NH(2))(2)Pt(1,3-DimeU-C5)(H(2)O)]X (X = NO(3)(-), 1a, ClO(4)(-), 1b) and subsequently with NaCl to give trans-(CH(3)NH(2))(2)Pt(1,3-DimeU-C5)Cl (2) or with NH(3) to yield trans-[(CH(3)NH(2))(2)Pt(1,3-DimeU-C5)(NH(3))]ClO(4) (3). In a similar way, (dien)Pt(II) forms [dienPt(1,3-DimeU-C5)](+) (4). Reactions leading to formation of 1 and 4 are slow, taking days. In contrast, Hg(CH(3)COO)(2) reacts fast with 1,3-DimeU to give (1,3-DimeU-C5)Hg(CH(3)COO) (5). Both 1-methyluracil (1-MeUH) and uridine (urdH) react with (dien)Pt(II) initially at N(3) and subsequently with either (dien)Pt(II) or Hg(CH(3)COO)(2) also at C(5) to give the diplatinated species 7 and 9 or the mixed PtHg complex 8. C(5) binding of either Pt(II) or Hg(II) is evident from coupling of uracil-H(6) with either (195)Pt or (199)Hg nuclei and (3)J values of 47-74 Hz (for Pt compounds) and 185-197 Hz (for Hg compounds). J values of Pt compounds are influenced both by the ligands trans to the uracil C(5) position and by the number of metal entities bound to a uracil ring. Both 2 and 5 were X-ray structurally characterized. 2: monoclinic system, space group P2(1)/c, a = 15.736(6) ?, b = 11.481(6) ?, c = 25.655 (10) ?, beta = 145.55(3) degrees, V = 2621.9(28) ?(3), Z = 4. 5: monoclinic system, space group P2(1)/c, a = 4.905(2) ?, b = 18.451(6) ?, c = 11.801(5) ?, beta = 94.47(3) degrees, V = 1064.77(72) ?(3), Z = 4.     

Solid-Phase Synthesis of a Monofunctional trans-a(2)Pt(II) Complex Tethered to a Single-Stranded Oligonucleotide

Cross-linking ability is possible with the oligonucleotide-tethered, monofunctional trans-Pt(II) complex shown. It was synthesized by a novel solid-phase approach comprising conjugation of immobilized tetrathymidylic acid with a trans-a(2)Pt(II) building unit, ammonolysis, and transformation of the resulting complex (R=1-N-cyclohexylmethylthyminate) into the chloro derivative (R=Cl). a=NH(2)CH(3), T=thymine.     

Pyrazine as a building block for molecular architectures with PtII

A series of pyrazine (pz) complexes containing cis-(NH(3))(2)Pt(II), (tmeda)Pt(II) (tmeda = N,N,N',N'-tetramethylethylenediamine), and trans-(NH(3))(2)Pt(II) entities have been prepared and characterized by X-ray crystallography and/or 1H NMR spectroscopy. In these compounds, the pz ligands act as monodentate (1-3) or bidentate bridging ligands (4-7). Three variants of the latter case are described: a dinuclear complex [Pt(II)]2 (4b), a cyclic tetranuclear [Pt(II)](4) complex (5), and a trinuclear mixed-metal complex [Pt2Ag] (7). Mono- and bidentate binding modes are readily differentiated by 1H NMR spectroscopy, and the assignment of pz protons in the case of monodentate coordination is aided by the observation of (195)Pt satellites. Formation of the open molecular box cis-[{(NH3)2Pt(pz)}4](NO3)8.3.67H2O (5) from cis-(NH3)2Pt(II) and pz follows expectations of the "molecular library approach" for the generation of a cyclic tetramer.     

Exploring the metal coordination properties of the pyrimidine part of purine nucleobases: isomerization reactions in heteronuclear Pt(II)/Pd(II) of 9-methyladenine

The synthesis and characterization of three heteronuclear Pt(2)Pd(2) (4, 5) and PtPd(2) (6) complexes of the model nucleobase 9-methyladenine (9-MeA) is reported. The compounds were prepared by reacting [Pt(NH(3))(3)(9-MeA-N7)](ClO(4))(2) (1) with [Pd(en)(H(2)O)(2)](ClO(4))(2) at different ratios r between Pt and Pd, with the goal to probe Pd(II) binding to any of the three available nitrogen atoms, N1, N3, N6 or combinations thereof. Pd(II) coordination occurs at N1 and at the deprotonated N6 positions, yet not at N3. 4 and 5 are isomers of [{(en)Pd}(2){N1,N6-9-MeA(-)-N7)Pt(NH(3))(3)}(2)](ClO(4))(6)·nH(2)O, with a head-head orientation of the two bridging 9-MeA(-) ligands in 4 and a head-tail orientation in 5. 6 is [{(en)Pd}(2)(OH)(N1,N6-9MeA(-)-N7)Pt(NH(3))(3)](ClO(4))(4)·4H(2)O, hence a condensation product between [Pt(NH(3))(3)(9-MeA-N7)](2+) and a μ-OH bridged dinuclear (en)Pd-OH-Pd(en) unit, which connects the N1 and N6 positions of 9-MeA(-) in an intramolecular fashion. 4 and 5, which slowly interconvert in aqueous solution, display distinct structural differences such as significantly different intramolecular Pd···Pd contacts (3.124 0(16) ? in 4; 2.986 6(14) ? in 5), among others. Binding of (en)Pd(II) to the exocyclic N6 atom in 4 and 5 is accompanied by a large movement of Pd(II) out of the 9-MeA(-) plane and a trend to a further shortening of the C6-N6 bond as compared to free 9-MeA. The packing patterns of 4 and 5 reveal substantial anion-π interactions.     

First example of the solid-state thermal cyclometalation of ligated benzophenone imine giving novel luminescent platinum(II) species

The (benzophenone imine)platinum(II) compounds trans-[PtCl2(Ph2C=NH)(RR'SO)] [R, R'=Me, Me (2); n-Pr, n-Pr (3); (CH2)4 (4); Me, Ph (5); Me, p-MeC6H4 (6)] were prepared by the reaction of Ph2C=NH with K[PtCl3(RR'SO)], obtained in situ from K2[PtCl4] and the corresponding sulfoxide, giving 2-6 as well as cis-[PtCl2(Ph2C=NH)2] (1) as a minor product. The complexes were characterized by 1H, 13C, and 195Pt NMR and IR spectroscopy, electrospray ionization mass spectrometry, and C, H, and N elemental analysis. The X-ray crystallography of 1 enables confirmation of the cis configuration of the complex, while in 2 and 4.1/2CHCl3, the imine and sulfoxide ligands are mutually trans. The solid-state structure of 4.1/2CHCl3 consists of two dimeric Pt moieties representing a rather weak Pt...Pt interaction. The dimeric architecture of 4.1/2CHCl3 is enhanced by the hydrogen bonding between imine H atoms and O atoms. The orthometalation of 1 and 2-6 proceeds both in the solid phase and in a toluene suspension, leading to the formation of [PtCl{Ph(C6H4)C=NH}(Ph2C=NH)] (7) and [PtCl{Ph(C6H4)C=NH}(RR'SO)] (8-12), respectively, isolated in nearly quantitative yields. Complexes 8-12 are emissive at room temperature both in solution (lambdaemmax approximately 535 nm) and in the solid state (lambdaemmax 560-610 nm), with excited-state lifetimes of ca. 300-600 ns, representing a new family of PtII-based luminescent complexes. Compounds 8 and 10 have been characterized by X-ray analysis, confirming the square-planar coordination geometry of the metal center with the almost planar platinacycles. In 8, the asymmetric unit contains two independent Pt molecules, while in 10, it includes four Pt molecules linked by the intermolecular hydrogen-bonding network between the NH group and Cl atoms.     

Unexpected metal-induced isomerisms and phosphoryl migrations in Pt(II) and Pd(II) complexes of the functional phosphine 2-(bis(diphenylphosphino)methyl)-oxazoline

The reaction of the functional diphosphine 1 [1 = 2-(bis(diphenylphosphino)methyl-oxazoline] with [PtCl(2)(NCPh)(2)] or [PdCl(2)(NCPh)(2)], in the presence of excess NEt(3), affords [Pt{(Ph(2)P)(2)C···C(···NCH(2)CH(2)O)}(2)] ([Pt(1(-H)-P,P)(2)], 3a) and [Pd{(Ph(2)P)(2)C···C(···NCH(2)CH(2)O)}(2)] ([Pd(1(-H)-P,P)(2)], 3b), respectively, in which 1(-H) is (oxazoline-2-yl)bis(diphenylphosphino)methanide. The reaction of 3b with 2 equiv of [AuCl(tht)] (tht = tetrahydrothiophene) afforded [Pd(1(-H)-P,N)(2)(AuCl)(2)] (4), as a result of the opening of the four-membered metal chelate since ligand 1(-H), which was P,P-chelating in 3b, behaves as a P,N-chelate toward the Pd(II) center in 4 and coordinates to Au(I) through the other P donor. In the absence of a base, the reaction of ligand 1 with [PtCl(2)(NCPh)(2)] in MeCN or CH(2)Cl(2) afforded the isomers [Pt{(Ph(2)P)(2)C═C(OCH(2)CH(2)NH)}(2)]Cl(2) ([Pt(1'-P,P)(2)]Cl(2) (5), 1' = 2-(bis(diphenylphosphino)methylene)-oxazolidine) and [Pt{(Ph(2)P)(2)C═C(OCH(2)CH(2)NH)}{Ph(2)PCH═C(OCH(2)CH(2)N(PPh(2))}]Cl(2) ([Pt(1'-P,P)(2'-P,P)]Cl(2) (6), 2' = (E)-3-(diphenylphosphino)-2-((diphenylphosphino)methylene)oxazolidine]. The P,P-chelating ligands in 5 result from a tautomeric shift of the C-H proton of 1 to the nitrogen atom, whereas the formation of one of the P,P-chelates in 6 involves a carbon to nitrogen phosphoryl migration. The reaction of 5 and 6 with a base occurred by deprotonation at the nitrogen to afford 3a and [Pt{(Ph(2)P)(2)C···C(···NCH(2)CH(2)O)}{Ph(2)PCH═COCH(2)CH(2)N(PPh(2))}]Cl ([Pt(1(-H)-P,P)(2'-P,P)]Cl (7)], respectively. In CH(2)Cl(2), an isomer of 3a, [Pt{Ph(2)P)(2)C···C(···NCH(2)CH(2)O)}{Ph(2)PC(PPh(2))═COCH(2)CH(2)N}] ([Pt(1(-H)-P,P)(1(-H)-P,N)] (8)), was obtained as a side product which contains ligand 1(-H) in two different coordination modes. Complexes 3b·4CH(2)Cl(2), 4·CHCl(3), 6·2.5CH(2)Cl(2), and 8·CH(2)Cl(2) have been structurally characterized by X-ray diffraction.     

[ZnN(CH2CH2NH2)2(CH2CH2N=CHC6H4O)]·Pic的合成与晶体结构

在不加任何碱的条件下,三[2-(亚水杨基胺)乙基]胺与苦味酸锌[Zn(Pic)26H2O]在乙醇中反应,得到了较为少见的多胺单缩合西夫碱配体的配合物[ZnN(CH2CH2NH2)2(CH2CH2N=CH-C6H4O)]Pic。化学式为C19H23N7O8Zn,Mr=542.81,晶体属三斜晶系,空间群为P,晶胞参数为a=0.7494(3),b=1.1917(5),c=1.3142(6)nm,a=78.111(7),b=79.093(7),g=78.577(7),V=1.1121(8)nm3,Dc=1.621g/cm3,m(MoKa)=1.167mm-1,Z=2,F(000)=560,在1.602s(I)的可观测点为2433个,最终偏离因子R=0.0555,wR=0.1139。配合物中Zn(II)与配体的4个N原子和1个O原子配位形成变形的三角双锥结构,桥头N和O为锥顶,4个配位N中桥头N与金属离子的配位作用最弱。晶体通过p-p堆积和分子内、分子间的氢键作用形成二维层状超分子结构。     

Binding affinities for models of biologically available potential Cu(II) ligands relevant to Alzheimer's disease: an ab initio study

A systematic study of the binding affinities of the model biological ligands X: = (CH3)2S, CH3S-, CH3NH2, 4-CH3-imidazole (MeImid), C6H5O-, and CH3CO2- to (NH3)i(H2O)3-iCu(II)-H2O (i = 3, 2, 1, 0) complexes has been carried out using quantum chemical calculations. Geometries have been obtained at the B3LYP/ 6-31G(d) level of theory, and binding energies, Delta, relative to H2O as a ligand, have been calculated at the B3LYP/6-311+G(2df,2p)//B3LYP/6-31G(d) level. Solvation effects have been included using the COSMO model, and the relative binding free energies in aqueous solution (Delta) have been determined at pH 7 for processes that are pH dependent. CH3S- (Delta = -16.0 to -53.5 kJ mol(-1)) and MeImid (Delta = -18.5 to -35.2 kJ mol(-1)) give the largest binding affinities for Cu(II). PhO- and (CH3)2S are poor ligands for Cu(II), Delta = 20.6 to -9.7 and 19.8 to -3.7 kJ mol(-1), respectively. The binding affinities for CH3NH2 range from -0.8 to -15.0 kJ mol(-1). CH3CO2- has Cu(II) binding affinities in the ranges Delta = -13.5 to -32.4 kJ mol(-1) if an adjacent OH bond is available for hydrogen bonding and Delta = 10.1 to -4.6 kJ mol(-1) if this interaction is not present. In the context of copper coordination by the Abeta peptide of Alzheimer's disease, the binding affinities suggest preferential binding of Cu(II) to the three histidine residues plus a lysine or the N-terminus. For a 3N1O Cu(II) ligand arrangement, it is more probable that the oxygen ligand comes from an aspartate/glutamate residue side chain than from the tyrosine at position 10. Methionine appears unlikely to be a Cu(II) ligand in Abeta.     

Substitution behaviour of novel dinuclear Pt(II) complexes with bio-relevant nucleophiles

The novel dinuclear Pt(II) complexes [{trans-Pt(NH(3))(2)Cl}(2)(μ-pyrazine)](ClO(4))(2) (Pt1), [{trans-Pt(NH(3))(2)Cl}(2)(μ-4,4'-bipyridyl)](ClO(4))(2)·DMF (Pt2), and [{trans-Pt(NH(3))(2)Cl}(2)(μ-1,2-bis(4-pyridyl)ethane)](ClO(4))(2) (Pt3), were synthesized. Acid-base titrations, and temperature and concentration dependent kinetic measurements of the reactions with biologically relevant ligands such as thiourea (Tu), glutathione (GSH) and guanosine-5'-monophosphate (5'-GMP) were studied at pH 2.5 and 7.2. The reactions were followed under pseudo-first-order conditions by stopped-flow and UV-vis spectrophotometry. (1)H NMR spectroscopy was used to follow the substitution of chloride in the complex [{trans-Pt(NH(3))(2)Cl}(2)(μ-4,4'-bipyridyl)](ClO(4))(2)·DMF by guanosine-5'-monophosphate (5'-GMP) under second-order conditions. The results indicate that the bridging ligand has an influence on the reactivity of the complexes towards nucleophiles. The order of reactivity of the investigated complexes is Pt1 > Pt2 > Pt3.     

N1 and N3 linkage isomers of neutral and deprotonated cytosine with trans-[(CH3NH2)2PtII

A series of complexes obtained from the reaction of trans-[(CH3NH2)2PtII] with unsubstituted cytosine (CH) and its anion (C), respectively, has been prepared and isolated or detected in solution: trans-[Pt(CH3NH2)2(CH-N3)Cl]Cl.H2O (1), trans-[Pt(CH3NH2)2(CH-N3)2](ClO4)2 (1a), trans-[Pt(CH3NH2)2(C-N3)2].2H2O (1b), trans-[Pt(CH3NH2)2(CH-N3)2](ClO4)(2).2DMSO (1c), trans-[Pt(CH3NH2)2(CH-N1)2] (NO3)(2).3H2O (2a), trans-[Pt(CH3NH2)2(C-N1)2].2H2O (2b), trans-[Pt(CH3NH2)2(CH-N1)(CH-N3)](ClO4)2 (3a), trans-[Pt(CH3NH2)2(C-N1)(C-N3)] (3b), and trans-[Pt(CH3NH2)2(N1-CN3)(N3-C-N1)Cu(OH)]ClO(4).1.2H2O (4). X-ray crystal structures of all these compounds, except 3a and 3b, are reported. Complex 2a is of particular interest in that it contains the rarer of the two 2-oxo-4-amino tautomer forms of cytosine, namely that with the N3 position protonated. Since the effect of PtII on the geometry of the nucleobase is minimal, bond lengths and angles of CH in 2a reflect, to a first approximation, those of the free rare tautomer. Compared to the preferred 2-oxo-4-amino tautomer (N1 site protonated) of CH, the rare tautomer in 2a differs particularly in internal ring angles (7-11 sigma). Formation of compounds containing the rare CH tautomers on a preparative scale can be achieved by a detour (reaction of PtII with the cytosine anion, followed by cytosine reprotonation) or by linkage isomerization (N3-->N1) under alkaline reaction conditions. Surprisingly, in water and over a wide pH range, N1 linkage isomers (3a, 2a) form in considerably higher amounts than can be expected on the basis of the tautomer equilibrium. This is particularly true for the pH range in which the cytosine is present as a neutral species and implies that complexation of the minor tautomer is considerably promoted. Deprotonation of the rare CH tautomers in 2a occurs with pKa values of 6.07 +/- 0.18 (1 sigma) and 7.09 +/- 0.11 (1 sigma). This value compares with pKa 9.06 +/- 0.09 (1 sigma) (average of both ligands) in 1a.     

Reaction of polynuclear platinum antitumor compounds with reduced glutathione studied by multinuclear (1H, 1H-15N gradient heteronuclear single-quantum coherence,and 195Pt) NMR spectroscopy

A possible explanation for the low bioavailability of platinum antitumor compounds is their high reactivity with the sulfur-containing tripeptide glutathione (GSH; deprotonated GSH = SG). GSH is located in the intracellular matrix of the cell with a normal concentration of 5-10 mM. In vivo, only a small fraction of the administered drug will migrate into the cell, resulting in relatively high concentrations of GSH compared to that of the drug. The products of the reactions of [[trans-PtCl(NH(3))(2)](2)-mu-[trans-Pt(NH(3))(2)(NH(2)(CH(2))(6)NH(2))(2)]](NO(3))(4) (BBR3464; 1,0,1/t,t,t, n = 6), [[trans-PtCl(NH(3))(2)](2)-mu-(H(2)N(CH(2))(6)NH(2))](NO(3))(2) (BBR3005; 1,1/t,t, n = 6), [[trans-PtCl(NH(3))(2)](2)-mu-(H(2)N(CH(2))(3)NH(2)(CH(2))(4)NH(2))]Cl(3) (BBR3571; 1,1/t,t-spermidine, n = 3, 4), and trans-[PtCl(2)(NH(3))(2)] (t-DDP) with reduced GSH in phosphate-buffered saline (pH 7.35) have been characterized by (1)H, (195)Pt, and (1)H(-)(15)N gradient heteronuclear single-quantum coherence NMR spectroscopy and high-performance liquid chromatography (HPLC) coupled with electrospray ionization time-of-flight mass spectrometry to determine likely metabolites of the complexes with GSH. Chemical shifts (NMR) and retention times (HPLC) established via analysis of the t-DDP profile served as a fingerprint to compare results obtained for the products afforded by the degradation of the polynuclear compounds by GSH. Identical kinetic profiles and chemical shifts between the metabolites and the t-DDP/GSH products allowed identification of the final product for the 1:2 Pt:GSH reaction as a dinuclear species [[trans-Pt(SG)(NH(3))(2)](2)-mu-SG], in which glutathione bridges the two platinum centers via only the sulfur atom.     

Quantum chemical studies on anion specificity of C<Superscript>α</Superscript>NN motif in functional proteins

Anion binding C^αNN motif is found in functionally important regions of protein structures. This motif based only on backbone atoms from three adjacent residues, recognizes free sulphate or phosphate ion as well as phosphate groups in nucleotides and in a variety of cofactors. The mode of anion recognition and microscopic picture of binding interaction remains unclear. Here we perform self-consistent quantum chemical calculations considering sulphate and phosphate bound C^αNN motif fragments from crystal structures of functional proteins in order to figure out microscopic basis of anion recognition. Our calculations indicate that stability and preference of the anion in the motif depends on the sequence of the motif. The stabilization energy is larger in case of polar residue containing motif fragment. Nitrogen atom of the polar residue of motif mainly participates in the coordination at the lowest energy levels. Anion replacement decreases stabilization energy along with coordination between motif atoms and oxygen atoms of anion shifted to higher energies, suggesting preference of the motif residues to specific anion. Our analysis may be helpful to understand microscopic basis of interaction between proteins and ionic species.     

Complex formation of isocytosine tautomers with PdII and PtII

Isocytosine (ICH) exists in solution as two major tautomers, the keto form with N1 carrying a proton (1a) and the keto form with N3 being protonated (1b). In water, 1a and 1b exist in equilibrium with almost equal amounts of both forms present. Reactions with a series of Pd(II) and Pt(II) am(m)ine species such as (dien)Pd(II), (dien)Pt(II), and trans-(NH(3))(2)Pt(II) reveal, however, a distinct preference of these metals for the N3 site, as determined by (1)H NMR spectroscopy. Individual species have been identified by the pD dependence of the ICH resonances. pK(a) values (calculated for H(2)O) for deprotonation of the individual tautomers complexes are 6.5 and 6.4 for the N3 linkage isomers of dienPd(II) and dienPt(II), respectively, as well as 6.2 and 6.0 for the N1 linkage isomers. The dimetalated species [(dienM)(2)(IC-N1,N3)](3+) (M = Pd(II) or Pt(II)) are insensitive over a wide range of pD. The crystal structure analysis of [(dien)Pd(ICH-N3)](NO(3))(2) is reported. Ab initio calculations have been performed for tautomer compounds of composition [(NH(3))(3)Pt(ICH)](2+), cis- and trans-[(NH(3))(2)PtCl(ICH)](+), as well as trans-[(NH(3))(2)Pt(ICH)(2)](2+). Without exception, N3 linkage isomers are more stable, in agreement with experimental findings. As to the reasons for this binding preference, an NBO (natural bond orbital) analysis for [(NH(3))(3)Pt(ICH-N3)](2+)strongly suggests that intramolecular hydrogen bonding between trans-positioned NH(3) ligands and the two exocyclic groups of the ICH is of prime importance. The calculations furthermore show a marked pyramidalization of the NH(2) group of ICH in the complex once the heterocyclic ligand forms a dihedral angle <90 degrees with the Pt coordination plane.     

Red-light photosensitized cleavage of DNA by (l-lysine)(phenanthroline base)copper(II) complexes

Ternary copper(II) complexes [Cu(l-lys)B(ClO4)](ClO4)(1-4), where B is a heterocyclic base, viz. 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3) and dipyrido[3,2-a:2',3'-c]phenazene (dppz, 4), are prepared and their DNA binding and photo-induced DNA cleavage activity studied (l-lys =l-lysine). Complex 2, structurally characterized by X-ray crystallography, shows a square-pyramidal (4 + 1) coordination geometry in which the N,O-donor l-lysine and N,N-donor heterocyclic base bind at the basal plane and the perchlorate ligand is bonded at the elongated axial site. The crystal structure shows the presence of a pendant cationic amine moiety -(CH2)4NH3+ of l-lysine. The one-electron paramagnetic complexes display a d-d band in the range of 598-762 nm in DMF and exhibit cyclic voltammetric response due to Cu(II)/Cu(I) couple in the range of 0.07 to -0.20 V vs. SCE in DMF-Tris-HCl buffer. The complexes having phenanthroline bases display good binding propensity to the calf thymus DNA giving an order: 4 (dppz) > 3 (dpq) > 2 (phen)> 1 (bpy). Control cleavage experiments using pUC19 supercoiled DNA and distamycin suggest major groove binding for the dppz and minor groove binding for the other complexes. Complexes 2-4 show efficient DNA cleavage activity on UV (365 nm) or visible light (694 nm ruby laser) irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. The amino acid l-lysine bound to the metal shows photosensitizing effect at red light, while the heterocyclic bases are primarily DNA groove binders. The dpq and dppz ligands display red light-induced photosensitizing effects in copper-bound form.     

Investigating bidentate and tridentate carbamoylmethylphosphine oxide ligand interactions with rare-Earth elements using electrospray ionization quadrupole ion trap mass spectrometry

Electrospray ionization (ESI) quadrupole ion trap mass spectrometry (QIT-MS) and collisionally activated dissociation (CAD) were used to evaluate the rare-earth binding properties of two hydrophobic carbamoylmethylphosphine oxide (CMPO) ligands, the normal bidentate variety, (t-BuC6H4)2P(O)CH2C(O)N(i-Bu)2 (A), a new potentially tridentate extractant, (t-BuC6H4)2P(O)CH[CH2C(O)N(i-Bu)2]C(O)N(i-Bu)2 (B), and tributyl phosphate. The mass spectral results obtained from analysis of 1% HNO3/methanol solution containing the ligands and dissolved lanthanide salts reveal that the favorable stoichiometries of the ligand/metal/nitrate complexes are 2:1:2 for the bidentate ligand A, 1:1:2 for the tridentate ligand B, and 3:1:2 for the monodentate tributyl phosphate. These observed stoichiometries correlate with the number of available binding sites on each ligand as well as with potential steric effects. Energy-variable collisionally activated dissociation experiments showed that for the 2:1:2 complexes involving ligand A or B, as the ionic radius of the bound metal decreased, the removal of nitric acid required less energy and resulted in less extensive spontaneous solvent coordination. This experimental trend suggests that, as the ionic radius of the lanthanide ion decreases, a pair of the carbamoylmethylphosphine ligands is able to more completely solvate the bound metal ion thereby weakening the nitrate-metal interaction.