Time-dependent binding mode of a cationic porphyrin dimer to poly[d(G-C)2] and Poly[d(A-T)2

The time-dependent binding mode of a porphyrin dimer to poly[d(G-C)2] and poly[d(A-T)2] was investigated by spectroscopic methods including absorption and circular and linear dichroism (CD and LD) spectroscopy. Immediately after mixing with poly[d(G-C)2], the porphyrin dimer exhibited red-shift and hypochromism in the absorption spectrum and negative CD and LD spectra. With further red-shift in absorption, the CD and LD magnitude in the Soret region became increasingly negative over time. After it was stabilized, the magnitude of the reduced LD (LDr) in the Soret region was larger than that in the DNA absorption region, indicating that the second porphyrin was also intercalated. Following the rapid intercalation of the first porphyrin, the very slow intercalation of the second followed with first-order kinetics. In the poly[d(A-T)2] case, a bisignate CD spectrum was observed in the Soret region suggesting stacking of the porphyrins. The small alteration in the CD spectrum and increased absorbance, which followed the initial rapid spectral change, was of the second order. This alteration in the spectral properties was attributed to the conformational change of poly[d(A-T)2] near the binding site because the overall shape of the CD spectrum was conserved in spite of the changes in the absorption spectrum.     

Monitoring the DNA binding kinetics of a binuclear ruthenium complex by energy transfer: evidence for slow shuffling

The semirigid binuclear ruthenium complex Delta,Delta-[mu-(11,11'-bidppz)(phen)(4)Ru(2)](4+) has been shown to rearrange slowly from an initial groove-bound nonluminescent state to a final intercalated emissive state by threading one of its bulky Ru(phen)(2) moieties through the DNA base stack. When this complex binds to poly[d(A-T)(2)], a further increase in emission from the complex is observed after completion of the intercalation, assigned to reorganization of the intercalated complex. We here report a study of the threading process in poly[d(A-T)(2)], in which the minor groove binding dye DAPI is used as an energy transfer probe molecule to assess the distribution of ruthenium complex during and also after the actual threading phase. The emission from DAPI is found to change with the same rate as the emission from the ruthenium complex, and furthermore, DAPI does not disturb the binding kinetics of the latter, justifying it as a good probe of both the threading and the reorganization processes. We conclude from the change in the emission from both DAPI and the ruthenium complex with time that DAPI-ruthenium interactions are most pronounced during the process of threading of the complex, suggesting that the complexes are initially threaded slightly anticooperatively and thereafter redistribute along the DNA to reach their thermodynamically most favorable distribution. The final distribution is characterized by a small but significant binding cooperativity, probably as a result of hydrophobic interactions between the complex ions despite their tetravalent positive charges. The mechanism of "shuffling" the complex along the DNA chain is discussed, i.e., whether the ruthenium complex remains threaded (requiring sequential base-pair openings) or if unthreading followed by lateral diffusion within the ionic atmosphere of the DNA and rethreading occurs.     

Binding of meso-tetrakis(N-methylpyridium-4-yl)porphyrin to triplex oligonucleotides: evidence for the porphyrin stacking in the major groove

Induced CD spectra of meso-tetrakis(N-methylpyridium-4-yl)porphyrin (TMPyP) complexed with d(A)12.d(T)12, d(G)12.d(C)12 duplex and d(A)12.[d(T)12]2, d(G)12.d(C)12.d(C)12+ triplex in the Soret band were compared in this study. When TMPyP is complexed with the duplex, a monomeric CD spectrum at a low [TMPyP]/[oligomer] ratio was apparent, while at a high mixing ratio, the excitonic CD was dominant. In contrast, when TMPyP was complexed with the triplex, the excitonic CD disappears at a relatively high mixing ratio, indicating the TMPyP exciton formation is inhibited by the third strand, which is located in the major groove. This observation indicates that the exciton is formed at the major groove of both AT- and GC-rich DNA, while the monomeric TMPyP binds at (or near) the minor groove of the AT site.     

四甲基吡啶卟啉与核酸相互作用的稳态和时间分辨光谱

采用稳态吸收和荧光光谱、圆二色谱和皮秒时间分辨荧光光谱手段, 研究了5,10,15,20-四[4-(N-甲基吡啶)]卟啉(TMPyP4)与腺嘌呤(A)、鸟嘌呤(G)、胸腺嘧啶(T)和胞嘧啶(C)等4种碱基, 以及相应的核苷、核苷酸和单链DNA的结合能力和光谱学性质. 研究结果发现, 嘌呤与TMPyP4的结合能力比嘧啶的强. 对于某一碱基系列, 结合能力强弱顺序依次为: 碱基~核苷<核苷酸<单链DNA. 时间分辨荧光谱研究发现, 除鸟嘌呤外, 核酸和TMPyP4复合物的荧光动力学均含有快(1~2 ns)和慢(约10 ns)两个衰减过程, 它们分别是由激基复合体和环境极性对激发态TMPyP4分子的影响所致. 单链DNA能诱导TMPyP4产生诱导圆二色信号, 而单分子(碱基、核苷、核苷酸)则无此功能.     

Aminoglycoside-nucleic acid interactions: remarkable stabilization of DNA and RNA triple helices by neomycin

The stabilization of poly(dA).2poly(dT) triplex, a 22-base DNA triplex, and poly(rA).2poly(rU) triple helix by neomycin is reported. The melting temperatures, the association and dissociation kinetic parameters, and activation energies (E(on) and E(off)) for the poly(dA).2poly(dT) triplex in the presence of aminoglycosides and other triplex binding ligands were determined by UV thermal analysis. Our results indicate that: (i) neomycin stabilizes DNA triple helices, and the double helical structures composed of poly(dA).poly(dT) are virtually unaffected. (ii) Neomycin is the most active and triplex-selective stabilization agent among all aminoglycosides, previously studied minor groove binders, and polycations. Its selectivity (DeltaT(m3-->2) vs DeltaT(m2)(-->)(1)) exceeds most intercalating drugs that bind to triple helices. (iii) Neomycin selectively stabilizes DeltaT(m3)(-->)(2) for a mixed 22-base DNA triplex containing C and T bases in the pyrimidine strand. (iv) The rate constants of formation of triplex (k(on)) are significantly enhanced upon increasing molar ratios of neomycin, making triplex association rates closer to duplex association rates. (v) E(on) values become more negative upon increasing concentration of aminoglycosides (paromomycin and neomycin). E(off) values do not show any change for most aminoglycosides except neomycin. (vi) Aminoglycosides can effectively stabilize RNA [poly(rA).2poly(rU)] triplex, with neomycin[being one of the most active ligands discovered to date (second only to ellipticine). (vii) The stabilization effect of aminoglycosides on triple helices is parallel to their toxic behavior, suggesting a possible role of intramolecular triple helix (H-DNA) stabilization by the aminoglycosides.     

Electrochemical and photophysical properties of DNA metallo-intercalators containing the ruthenium(II) tris(1-pyrazolyl)methane unit

Three new ruthenium(II) complexes containing the tris(1-pyrazolyl)methane (tpm) ligand have been prepared: [Ru(tpm)(L)(dppn)]n+ (where n = 1; L = Cl (5), n = 2; L = MeCN (6) and pyridine (7); dppn = benzo[i]dipyrido[3,2-a:2',3'-c]phenazine). Complex 6 was structurally characterized by single-crystal X-ray diffraction. Binding parameters of these complexes with calf thymus DNA are reported and compared to those obtained for a previously reported monocation, [RuCl(tpm)(dppz)]+. Binding studies with the dications and the synthetic oligonucleotides poly(dA).poly(dT) and poly(dG).poly(dC) have also been determined. Photophysical and electrochemical properties of 5-7 have been investigated and compared with their dipyridophenazine (dppz) analogues.     

Molecular electrotatic potential of a triple stranded helix: Poly(dT)·poly(dA)·poly(dT)

The molecular electrostatic potential of the triple helix poly(dT)·tpoly(dA)·poly(dT) is calculated, and the results are examined in relation to those obtained for its component double and single helical parts. For the double helix presenting the standard Watson–Crick hydrogen bonds, the deepest potentials are formed on the side of the major groove, a situation similar to that observed in the A-DNA duplex. For the double helix presenting Hoogsteen-type hydrogen bonds the deepest potentials lie in the major groove, on the side of the pyrimidine strand. In the triple helix the deepest potentials are located in the major groove in a narrow zone over the thymine bases of the Watson–Crick pair.     

Water-soluble porphyrins appending platinum(II) complexes as binders for synthetic nucleic acid polymers

Water-soluble porphyrins containing four platinum(II) complexes per molecule, [5alpha,10beta,15alpha,20beta-tetrakis(2-trans-(alpha,beta,alpha,beta-trans-Pt) and cis-(alpha,beta,alpha,beta-cis-Pt) [PtCl(NH(3))(2)]N-2-aminophenylporphyrin)], were synthesized and characterized. The binding of synthetic nucleotide polymers (poly(dG)-poly(dC), poly(dA)-poly(dT)) to the porphyrins was examined spectrophotometrically in aqueous solution. UV-vis spectral data suggested that these porphyrins bind to the nucleic acids by coordinative and Coulomb interactions.     

Neomycin-neomycin dimer: an all-carbohydrate scaffold with high affinity for AT-rich DNA duplexes

A dimeric neomycin-neomycin conjugate 3 with a flexible linker, 2,2'-(ethylenedioxy)bis(ethylamine), has been synthesized and characterized. Dimer 3 can selectively bind to AT-rich DNA duplexes with high affinity. Biophysical studies have been performed between 3 and different nucleic acids with varying base composition and conformation by using ITC (isothermal calorimetry), CD (circular dichroism), FID (fluorescent intercalator displacement), and UV (ultraviolet) thermal denaturation experiments. A few conclusions can be drawn from this study: (1) FID assay with 3 and polynucleotides demonstrates the preference of 3 toward AT-rich sequences over GC-rich sequences. (2) FID assay and UV thermal denaturation experiments show that 3 has a higher affinity for the poly(dA)·poly(dT) DNA duplex than for the poly(dA)·2poly(dT) DNA triplex. Contrary to neomycin, 3 destabilizes poly(dA)·2poly(dT) triplex but stabilizes poly(dA)·poly(dT) duplex, suggesting the major groove as the binding site. (3) UV thermal denaturation studies and ITC experiments show that 3 stabilizes continuous AT-tract DNA better than DNA duplexes with alternating AT bases. (4) CD and FID titration studies show a DNA binding site size of 10-12 base pairs/drug, depending upon the structure/sequence of the duplex for AT-rich DNA duplexes. (5) FID and ITC titration between 3 and an intramolecular DNA duplex [d(5'-A(12)-x-T(12)-3'), x = hexaethylene glycol linker] results in a binding stoichiometry of 1:1 with a binding constant ～10(8) M(-1) at 100 mM KCl. (6) FID assay using 3 and 512 hairpin DNA sequences that vary in their AT base content and placement also show a higher binding selectivity of 3 toward continuous AT-rich than toward DNA duplexes with alternate AT base pairs. (7) Salt-dependent studies indicate the formation of three ion pairs during binding of the DNA duplex d[5'-A(12)-x-T(12)-3'] and 3. (8) ITC-derived binding constants between 3 and DNA duplexes have the following order: AT continuous, d[5'-G(3)A(5)T(5)C(3)-3'] > AT alternate, d[5'-G(3)(AT)(5)C(3)-3'] > GC-rich d[5'-A(3)G(5)C(5)T(3)-3']. (9) 3 binds to the AT-tract-containing DNA duplex (B* DNA, d[5'-G(3)A(5)T(5)C(3)-3']) with 1 order of magnitude higher affinity than to a DNA duplex with alternating AT base pairs (B DNA, d[5'-G(3)(AT)(5)C(3)-3']) and with almost 3 orders of magnitude higher affinity than a GC-rich DNA (A-form, d[5'-A(3)G(5)C(5)T(3)-3']).     

Synthesis of tris- and tetrakis(pyrazol-1-yl)borate gold(III) complexes. Crystal structures of [Au[kappa(2)-N,N'-BH(Pz)(3)]Cl(2)] (pz = pyrazol-1-yl) and [Au[kappa(2)-N,N'-B(Pz)(4)](kappa(2)-C,N-C(6)H(4)CH(2)NMe(2)-2)]ClO(4).CHCl(3)

Na[BH(pz)(3)] and Na[AuCl(4)].2H(2)O react in water (1:1) to give [Au[kappa(2)-N,N'-BH(pz)(3)]Cl(2)] (1) or, in the presence of NaClO(4) (2:1:1), the cationic complex [Au[kappa(2)-N,N'-BH(pz)(3)](2)]ClO(4) (2). The reactions of Na[B(pz)(4)] with the cyclometalated gold complexes [AuRCl(2)] and NaClO(4) (1:1:1) produce [Au[kappa(2)-N,N'-B(pz)(4)](R)]ClO(4) [R = kappa(2)-C,N-C(6)H(4)CH(2)NMe(2)-2 (3)] or [Au[kappa(2)-N,N'-B(pz)(4)](R)Cl] [R = C(6)H(3)(N=NC(6)H(4)Me-4')-2-Me-5 (4)], respectively, although 4 is better obtained in the absence of NaClO(4). The crystal structures of 1 and 3.CHCl(3) are reported. Both complexes display the gold center in square planar environments, two coordination sites being occupied by the chelating poly(pyrazolyl)borate ligands.     

Synthesis and solution properties of poly(methacrylate)s with semipolar structures on the side chains

Poly{2‐(N,N‐dimethylamino)ethyl methacrylate [poly(DMMA)]}, which was prepared by radical polymerization initiated with dimethyl 2,2‐azobis(2‐methylpropionate), was reacted with hydrogen peroxide, diethyl sulfate, and chloroacetic acid to yield poly[N,N‐dimethyl‐N‐(2‐methacryloyloxyethyl)amine N‐oxide] [poly(DMANO)], poly[N‐ethyl‐N,N‐dimethyl‐N‐(2‐methacryloyloxyethyl)ammonium ethyl sulfate] [poly(EDMES)], and poly[N,N‐dimethyl‐N‐(2‐methacryloyloxy)ethylammonioacetate] [poly(DMEAA)] as ion‐containing water‐soluble polymers, respectively. The solution properties of these charged polymers were compared via the reduced viscosities of these three charged polymers in aqueous solutions as a function of the concentration. Poly(EDMES) showed typical polyelectrolyte behavior, and the other two polymers [poly(DMANO) and poly(DMEAA)] exhibited antipolyelectrolyte behavior. Furthermore, the antipolyelectrolyte behavior was different for poly(DMANO) and poly(DMEAA); that is, poly(DMANO) was less dependent on small electrolytes. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 129–141, 2005     

Synthesis, characterization, and DNA-binding and -photocleavage properties of water-soluble lanthanide porphyrinate complexes

A series of cationic lanthanide porphyrinate complexes of the general formula [(Por)Ln(H(2)O)(3)](+) (Ln(3+)=Yb(3+) and Er(3+)) were synthesized in moderate yields through the interaction of meso-pyridyl-substituted porphyrin free bases (H(2)Por) with [Ln{N(SiMe(3))(2)}(3)]·x[LiCl(thf)(3)], and the corresponding neutral derivatives [(Por)Ln(L(OMe))] (L(OMe)(-)=[(η(5)-C(5)H(5))Co{P(=O)(OMe)(2)}(3)](-)) were also prepared from [(Por)Ln(H(2)O)(3)](+) by the addition of the tripodal anion, L(OMe)(-), an effective encapsulating agent for lanthanide ions. Furthermore, the water-soluble lanthanide(III) porphyrinate complexes--including [(cis-DMPyDPP)Yb(H(2)O)(3)]Cl(3) (cis-DMPyDPP=5,10-bis(N-methylpyridinium-4'-y1)-15,20-di(phenyl)porphyrin), [(trans-DMPyDPP)Yb(H(2)O)(3)]Cl(3) (trans-DMPyDPP=5,15-bis(N-methylpyridinium-4'-y1)-10,20-di(phenyl)porphyrin), [(TMPyP)Yb(L(OMe))]I(4), and [(TMPyP)Er(L(OMe))]I(4) (TMPyP=tetrakis(N-methylpyridinium-4-y1)porphyrin)--were obtained by methylation of the corresponding complexes with methyl iodide and unambiguously characterized. The binding interactions and photocleavage activities of the water-soluble lanthanide(III) porphyrinate complexes towards DNA were investigated by UV-visible, fluorescence, and near-infrared luminescence spectroscopy, as well as circular dichroism and gel electrophoresis.     

Label-free emission assay of mercuric ions using DNA duplexes of poly(dT)

In this study, an assay to quantify the presence of mercuric ions and methyl mercury by double-stranded DNA containing a poly(dT) sequence was developed using a light switch compound, Ru(phen)(2)(dppz)(2+) (1), which is known to intercalate into double-stranded DNA. Upon treatment with mercuric ions, the metal-to-ligand charge transfer (MLCT) emission derived from the intercalation of 1 was reduced due to the formation of DNA duplexes containing T-Hg(2+)-T base pairs by the dehybridization of poly(dT)-poly(dA) duplexes at room temperature. As the concentration of Hg(2+) was increased, the emission of 1 gradually decreased. This label-free method had a detection limit of 5 nM. Other metal ions, such as K(+), Ag(+), Ca(2+), Mg(2+), Zn(2+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Cd(2+), Cr(3+), Fe(3+), had no significant effect on reducing emission. This emission method can differentiate matched and mismatched poly(dT) sequences based on the dehybridization rate of dsDNA and the rate decreased in the order of T(10)C·A(11)～ T(10)A·A(11) > T(10)G·A(11) > T(11)·A(11).     

Synthesis and nucleic acid-binding properties of water-soluble porphyrins appending platinum(II) complexes.

We synthesized two water-soluble porphyrins appending platinum(II) complexes [alpha,beta-(4a) and alpha,alpha-(4b) 5,15-bis(2-trans-[PtCl(NH3)2]N-2-aminoethylaminocarbonylphenyl) 2,3,7,8,12,13,17,18-octamethylporphyrin] and studied their reactions with a variety of nucleic acids [disodium adenosine-5'-monophosphate (AMP), disodium guanosine-5'-monophosphate (GMP), disodium thymidine-5'-monophosphate (TMP), disodium cytidine-5'-monophosphate (CMP), synthetic polymer poly(dG)-poly(dC), poly(dA)-poly(dT)] by 1H-NMR, UV-vis and FAB-MS spectroscopies. Based on the denaturation experiments of synthetic nucleic acid polymers, we conclude that the presence of the porphyrins (5.6 microM) does not cause significant changes in the melting temperature of poly(dA)-poly(dT) (28 microM) (deltaT=1 degrees C) and shows reannealing. On the other hand, gradual melting of poly(dG)-poly(dC) (28 microM) occurs at a low temperature (deltaT= -27 degrees C) in the presence of the porphyrins (5.6 microM), and the solutions do not show reannealing phenomena. The results of UV-vis and 1H-NMR experiments revealed that the porphyrins bind to guanine bases and that the porphyrins bind to GMP more strongly than to the other nucleotides. The binding modes between the porphyrins and synthetic nucleic acids are affected more by the coordination of the nucleobase [poly(dG)-poly(dC)] to the Pt(II) in the porphyrins than by Coulomb and hydrophobic interactions.     

Base-specific and enantioselective studies for the DNA binding of iron(II) mixed-ligand complexes containing 1,10-phenanthroline and dipyrido[3,2-a:2',3'-c]phenazine

Base specificity and enantioselectivity for the DNA binding of [Fe(phen)2(dppz)]2+ (phen=1,10-phenanthroline and dppz=dipyrido[3,2-a:2',3'-c]phenazine) have been studied by determining the equilibrium binding constant (Kb) of the iron(II) complex to calf thymus DNA (ct-DNA), poly[(dA-dT)2], poly[(dG-dC)2] and poly[(dI-dC)2] using spectrophotometric titration and by monitoring the CD spectral profile of the iron(II) complex in the presence and absence of different types of DNA using circular dichroism (CD) spectroscopy, respectively. It has been shown that [Fe(phen)2(dppz)]2+ prefers to intercalate into the A-T and I-C sequences of poly[(dA-dT)2] and poly[(dI-dC)2] rather than into the G-C sequences of poly[(dG-dC)2] or into the base pairs of ct-DNA. In contrast to previous reports, it is a surprising observation that the enantioselectivity of the DNA binding for [Fe(phen)2(dppz)]2+ is base-dependent in nature. The Delta-enantiomer of [Fe(phen)2(dppz)]2+ is preferentially intercalated into the base pairs of poly[(dG-dC)2] or ct-DNA as indicated by its CD spectral profiles. On the other hand, the Lambda-enantiomer of [Fe(phen)2(dppz)]2+ is favorably intercalated into poly[(dA-dT)2] or poly[(dI-dC)2] as suggested by the opposite CD spectral profile. This preferential binding of Lambda-[Fe(phen)2(dppz)]2+)for the A-T sequence may be attributed to the fact that the binding site for the A-T sequence is relatively facile and thus the steric effect caused by the ancillary (non-intercalated) phen ligands is alleviated. The degree of enantioselectivity represented by inversion constants (Kinv) decreases as the salt concentration in the solution increases, indicating that electrostatic interaction is also operating in the ct-DNA-binding events of the iron (II) complex.     

Comparison of the heat- and pressure-induced helix-coil transition of two DNA copolymers

The helix-coil transition of poly[d(I-C)] and poly[d(A-T)] was studied as a function of hydrostatic pressure, temperature, and sodium ion concentration. These studies were undertaken in light of a recently published phase diagram for double stranded nucleic acids [Dubins et al. J. Am. Chem. Soc. 2001, 123, 9254-9259]. The sign and magnitude of the volume change for the heat-induced helix-coil transition, DeltaV(T), of poly[d(I-C)] and poly[d(A-T)] were dependent on the helix-coil transition temperature, T(M), at atmospheric pressure. The sign of DeltaV(T) changed from negative to positive as T(M) was increased by increasing the sodium ion concentration. For poly[d(I-C)], DeltaV(T) = 0 cm(3) mol(-1), when the sodium ion concentration is such that the spectroscopically monitored T(M) = 55 degrees C at atmospheric pressure. For poly[d(A-T)], the value of DeltaV(T) = 0 under conditions such that T(M) = 47 degrees C at atmospheric pressure. Negative values of DeltaV(T) imply that the helical form is destabilized at high pressure. Under experimental conditions where the DeltaV(T) for the transition is negative, the transition could be caused by increasing the pressure under isothermal conditions. At temperatures below T(M) measured at atmospheric pressure the midpoint of the pressure-induced helix-coil transition, P(M), decreases with increasing temperature. The volume change of the pressure-induced transitions helix-coil transition, DeltaV(P), was calculated assuming a two-state model. The magnitude of DeltaV(P) (per cooperative length) was much larger than the volume change (per base pair) measured for the heat-induced transition, DeltaV(T), calculated using the Clapeyron equation. The ratio of these two volume changes was used to calculate the cooperative length for the pressure-induced transition. This parameter depends strongly on temperature, becoming greater closer to T(M) measured at atmospheric pressure. At temperatures approaching T(M) the magnitude of the cooperative length of the pressure-induced transition is approximately twice that observed for the heat-induced transition (N(T)). On the basis of the temperature dependence of the DeltaV(T) for the two polymers the coefficient of thermal expansion of the two polymers was found to be 0.17 and 0.16 cm(3) K(-1) mol(-1) for poly[d(I-C)] and poly[d(A-T)], respectively.     

Fine-tuning water exchange on Gd(III) poly(amino carboxylates) by modulation of steric crowding

In the objective of optimizing water exchange rate on stable, nine-coordinate, monohydrated Gd(III) poly(amino carboxylate) complexes, we have prepared monopropionate derivatives of DOTA4- (DO3A-Nprop4-) and DTPA5- (DTTA-Nprop5-). A novel ligand, EPTPA-BAA(3-), the bisamylamide derivative of ethylenepropylenetriamine-pentaacetate (EPTPA5-) was also synthesized. A variable temperature 17O NMR study has been performed on their Gd(III) complexes, which, for [Gd(DTTA-Nprop)(H2O)]2- and [Gd(EPTPA-BAA)(H2O)] has been combined with multiple field EPR and NMRD measurements. The water exchange rates, k(ex)(298), are 8.0 x 10(7) s(-1), 6.1 x 10(7) s(-1) and 5.7 x 10(7) s(-1) for [Gd(DTTA-Nprop)(H2O)]2-, [Gd(DO3A-Nprop)(H2O)]- and [Gd(EPTPA-BAA)(H2O)], respectively, all in the narrow optimal range to attain maximum proton relaxivities, provided the other parameters (electronic relaxation and rotation) are also optimized. The substitution of an acetate with a propionate arm in DTPA5- or DOTA4- induces increased steric compression around the water binding site and thus leads to an accelerated water exchange on the Gd(III) complex. The k(ex) values on the propionate complexes are, however, lower than those obtained for [Gd(EPTPA)(H2O)]2- and [Gd(TRITA)(H2O)]- which contain one additional CH(2) unit in the amine backbone as compared to the parent [Gd(DTPA)(H2O)]2- and [Gd(DOTA)(H2O)]-. In addition to their optimal water exchange rate, [Gd(DTTA-Nprop)(H2O)]2- has, and [Gd(DO3A-Nprop)(H2O)]- is expected to have sufficient thermodynamic stability. These properties together make them prime candidates for the development of high relaxivity, macromolecular MRI contrast agents.     

Molybdenum- and tungsten(II) monometallic 3-(2-pyridyl)pyrazole and bimetallic 3-(2-pyridyl)pyrazolate complexes

Molybdenum and tungsten complexes containing the pypzH (3-(2-pyridyl)pyrazole) ligand as a chelating bidentate are prepared: [Mo(CO)(4)(pypzH)], cis-[MoBr(η(3)-allyl)(CO)(2)(pypzH)], cis-[MoCl(η(3)-methallyl)(CO)(2)(pypzH)], [MI(2)(CO)(3)(pypzH)] (M = Mo, W) from [Mo(CO)(4)(NBD)] or the adequate bis(acetonitrile) complexes. The deprotonation of the molybdenum allyl or methallyl complexes affords the bimetallic complexes [cis-{Mo(η(3)-allyl)(CO)(2)(μ(2)-pypz)}](2) or [cis-{Mo(η(3)-methallyl)(CO)(2)(μ(2)-pypz)}](2) (μ(2)-pypz = μ(2)-3-(2-pyridyl-κ(1)N)pyrazolate-2κ(1)N). The allyl complex was subjected to an electrochemical study, which shows a marked connection between both metallic centres through the bridging pyridylpyrazolates.     

A series of dinuclear homo- and heterometallic complexes with two or three bridging sulfido ligands derived from the tungsten tris(sulfido) complex [Et(4)N][(Me(2)Tp)WS(3)] (Me(2)Tp = hydridotris(3,5-dimethylpyrazol-1-yl)borate)

The generation of heterobimetallic complexes with two or three bridging sulfido ligands from mononuclear tris(sulfido) complex of tungsten [Et(4)N][(Me(2)Tp)WS(3)] (1; Me(2)Tp = hydridotris(3,5-dimethylpyrazol-1-yl)borate) and organometallic precursors is reported. Treatment of 1 with stoichiometric amounts of metal complexes such as [M(PPh(3))(4)] (M = Pt, Pd), [(PtMe(3))(4)(micro(3)-I)(4)], [M(cod)(PPh(3))(2)][PF(6)] (M = Ir, Rh; cod = 1,5-cyclooctadiene), [Rh(cod)(dppe)][PF(6)] (dppe = Ph(2)PCH(2)CH(2)PPh(2)), [CpIr(MeCN)(3)][PF(6)](2) (Cp = eta(5)-C(5)Me(5)), [CpRu(MeCN)(3)][PF(6)], and [M(CO)(3)(MeCN)(3)] (M = Mo, W) in MeCN or MeCN-THF at room temperature afforded either the doubly bridged complexes [Et(4)N][(Me(2)Tp)W(=S)(micro-S)(2)M(PPh(3))] (M = Pt (3), Pd (4)), [(Me(2)Tp)W(=S)(micro-S)(2)M(cod)] (M = Ir, Rh (7)), [(Me(2)Tp)W(=S)(micro-S)(2)Rh(dppe)], [(Me(2)Tp)W(=S)(micro-S)(2)RuCp] (10), and [Et(4)N][(Me(2)Tp)W(=S)(micro-S)(2)W(CO)(3)] (12) or the triply bridged complexes including [(Me(2)Tp)W(micro-S)(3)PtMe(3)] (5), [(Me(2)Tp)W(micro-S)(3)IrCp][PF(6)] (9), and [Et(4)N][(Me(2)Tp)W(micro-S)(3)Mo(CO)(3)] (11), depending on the nature of the incorporated metal fragment. The X-ray analyses have been undertaken to clarify the detailed structures of 3-5, 7, and 9-12.