Association of polynucleotides with nucleolipid bilayers driven by molecular recognition

This contribution reports on the interaction of ss-polynucleotides of various length and sequence with liposomal dispersions of anionic lipids. No appreciable structural and morphological variations were detected for POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-glycerol) liposomes, as expected from the high negative charge density both of liposomal surface and of the poly or oligonucleotide. Conversely, when similarly charged POPN nucleolipids (1-palmitoyl-2-oleoylphosphatidyl-nucleosides) were used, meaningful differences could be observed both on size and morphology of the mixed aggregates. The comparison with POPG/nucleic acids mixed systems points to the conclusion that the driving force for association of nucleolipid liposomes with nucleic acids can be ascribed to selective interactions at the polar head level which overcome electrostatic repulsion. Dynamic light scattering, Cryo-TEM and circular dichroism provided an ensemble of results where an interesting dependence on the polynucleotide base nature and contour length emerges. The extent of interaction can be modulated, in terms of size of the complexes, by choice of background buffer, ionic strength and polynucleotide length.     

Interaction of Ca2+ with uracil and its thio derivatives in the gas phase

The structures and relative stabilities of the complexes formed by uracil and its sulfur derivatives, namely, 2-thio-, 4-thio, and 2,4-dithio-uracil when interacting with Ca(2+) in the gas phase have been analyzed by means of density functional theory (DFT) calculations carried out at the B3LYP/6-311++G(3df,2p)//B3LYP/6-31+G(d,p) level. For uracil and 2,4-dithiouracil, where the two basic sites are the same, Ca(2+) attachment to the heteroatom at position 4 is preferred. However, for the systems where both types of basic centers, a carbonyl or a thiocarbonyl group, are present, Ca(2+)-oxygen association is favored. The most stable complexes correspond to structures with Ca(2+) bridging between the heteroatom at position 2 of the 4-enol (or the 4-enethiol) tautomer and the dehydrogenated ring nitrogen, N3. The enhanced stability of these enolic forms is two-fold, on the one hand Ca(2+) interacts with two basic sites and on the other triggers a significant aromatization of the ring. Besides, Ca(2+) association has a clear catalytic effect on the tautomerization processes which connect the oxo-thione forms with the enol-enethiol tautomers. Hence, although the enol-enethiol tautomers of uracil and its thio derivatives should not be observed in the gas phase, the corresponding Ca(2+) complexes are the most stable species and should be accessible, because the tautomerization barriers are smaller than the Ca(2+) binding energies.     

Letter: collision-induced dissociation of [metal(L)(2)](2+) complexes (metal = Cu, Ca and Mg) of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine allows distinction of the acyl groups at the sn1 and sn2 positions

The collision induced dissociation (CID) spectra of the divalent metal complexes of 1-palmitoyl-2-oleoyl-sn- glycero-3-phosphocholine, [Metal(lI)(L)(2)](2+) (where metal = Cu(2+), Mg(2+) and Ca(2+), L = [16:0/18:1GPCho]), formed by electrospray ionization, reveal interesting metal dependant fragmentation chemistry. Six main classes of reaction are observed corresponding to: two competing carboxylate abstraction pathways (from the sn1 and sn2 positions); phosphate abstraction; competing losses of the two different carboxylic acids from the sn1 and sn2 positions; loss of a protonated ligand, [L + H](+). The relative ratios of the competing carboxylate abstraction reactions are dependant on the metal, with the Cu and Ca complexes favouring the abstraction of the larger carboxylate (18:1) and the Mg complex favoring the abstraction of the smaller carboxylate (16:0).     

Formation of interfacial milk protein complexation to stabilize oil-in-water emulsions against calcium

The interactions between cationic liposomes doped with the anionic nucleolipid 1,2-dipalmitoyl-sn-glycero-3-cytidine diphosphate (DP-Cyt) and deoxyribonucleic acid (DNA) were investigated. Toward this goal, new liposomal and lipoplex formulations characterized by the presence of the anionic amphiphile DP-Cyt were proposed. The effects of incorporation of the cytosine functionalized lipid DP-Cyt into the cationic bilayers were analyzed by means of electrophoretic mobility, dynamic light scattering (DLS) and fluorescence spectroscopy techniques. These approaches allowed us to follow the DNA condensation process and to identify specific electrokinetic characteristics of liposome and DNA-liposome complexes formation. Specifically, DP-Cyt liposomes and DNA were shown to form electrically stable or unstable complexes depending on the charge ratio between the phosphate group of DNA and the cationic lipid. Remarkably, a prominent role for DP-Cyt in enhancing the DNA binding capacity on liposomes was demonstrated. Zeta potential experiments performed on systems with different liposomes/DNA ratio showed that the value of the charge neutralization point is a function of the content of the incorporated DP-Cyt. As a whole, our data demonstrate that the association of cationic DP-Cyt doped liposomes with DNA is driven by both electrostatic interaction and additional specific interactions at the polar head level based on the cytidine nucleobase.     

Capillary electrophoresis of liposomes functionalized for protein binding

CE enabled assessing the attachment of hexa-histidine-tagged proteins to functionalized phospholipid liposomes. The liposomes were made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, phosphatidyl-ethanolamine, cholesterol and distearoyl-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol) in a molar ratio of 29:26:40:5. The unilamellar vesicles, which had an average diameter of 170 nm, were labelled by inclusion of FITC-dextran for fluorescence detection. CE was carried out in poly(vinyl alcohol) (PVA)-coated capillaries at 25 degrees C with a BGE consisting of Tris-HCl (50 mM, pH 8.0). For conjugation of the liposomes with the proteins (soluble synthetic receptor fragments with molecular mass of 60 and 70 kDa, respectively), Ni(2+) was implanted into the vesicle surface by an anchor lipid containing a nitrilotriacetate acid (NTA) group as complexation agent for the metal ions. The difference in surface charge enabled the separation of the different species of interest by CE: plain vesicles, vesicles functionalised with Ni-NTA, vesicle-protein complexes and the species formed upon removal of the Ni-ions by complexation with EDTA. Loss of the Ni-ions resulted in the release of the proteins and the reappearance of the plain Ni-free NTA-liposome species in the electropherograms.     

Synthesis and spectroscopic and structural characterization of two novel photoactivatable Ca2+ compounds

Two novel photoactivatable Ca(2+) compounds were synthesized to achieve a fast concentration jump of calcium ions in solution; this is of paramount importance for investigating the physiological cellular response. The light-sensitive ligands 4-(2-nitrophenyl)-3,6-dioxaoctane dioic acid (H2L1) and 4-(4,5-dimethoxy-2-nitrophenyl)-3,6-dioxaoctane dioic acid (H2L2) were generated by multistep syntheses, and the corresponding calcium complexes, Ca1 and Ca2, were isolated and characterized. The solution equilibria of H2L1 and H2L2 with Ca2+ were investigated; for both ligands, the formation of a 1:2 Ca2+/ligand species is detected and the complete characterization is presented. The crystal structures of Ca1 and Ca2 were determined. In Ca1 the solid state assembly is attained by a polymeric association of [(CaL1(H2O))2(mu-OH2)] dimeric units. Each calcium ion coordinates four oxygen atoms of one ligand (two ethereal, one carboxylic, and one bridging carboxylic oxygen atom), one water molecule, one bridging water molecule, and a carboxylate group of the other ligand within the dimer. The octacoordination of the metal is completed by an interaction with the adjacent dimeric unit. The crystal structure of the complex Ca2 does not show a polymeric nature, but it is a centrosymmetric dimer. The coordination number of the metal ion is still 8:4 oxygen atoms of the ligand; 3 water molecules; 1 bridging carboxylate group. A preliminary study of the photochemical features of the complexes Ca1 and Ca2 is reported: photoexcitation by a nanosecond pulsed UV laser induces the cleavage of the ligand. This drastically reduces the affinity of the ligand toward Ca2+, which is then released in solution.     

Zn2+,Cu2+及Ni2+对二甲双胍的配合作用及降血糖活性研究

二甲双胍盐酸盐、硝酸盐及与Zn²⁺, Cu²⁺, Ni²⁺三种金属离子配合物的结构特点、电荷分布和二甲双胍配合物对四氧嘧啶糖尿病小鼠血糖影响的研究表明:Zn²⁺配合物表现为较为少见的单齿配位,而Cu²⁺, Ni²⁺配合物表现为双齿配位.进一步电荷分布计算发现,与端基N原子相比,二甲双胍的桥基N原子具有较高的负电荷.三种金属离子配合物对四氧嘧啶糖尿病小鼠血糖的影响研究显示,桥基N配位掩蔽后,二甲双胍的降血糖功能丧失.说明桥基N对二甲双胍的降血糖作用具有重要意义.     

Electron capture dissociation of complexes of diacylglycerophosphocholine and divalent metal ions: Competition between charge reduction and radical induced phospholipid fragmentation

Divalent metal complexes of phosphocholines, [Metal(II)(L)(n)](2+) (where Metal=Cu(2+), Co(2+), Mg(2+), and Ca(2+), L=1,2-dihexanoyl-sn-glycero-3-phosphocholine [6:0/6:0GPCho] and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [16:0/18:1GPCho] and n=2-5), were formed upon electrospray ionization mass spectrometry (ESI/MS) of 8 mM solution of phosphocholine (L) with 4 mM metal salt (Metal). The electron capture dissociation (ECD) reactions of these [Metal(II)(L)(n)](2+) complexes were examined via Fourier-transform ion-cyclotron resonance mass spectrometry. A rich and complex chemistry was observed, including charge reduction and fragmentation involving losses of a methyl radical, trimethylamine, and the acyl chains. The predominant reaction channel was dependent on the size (n) of the complex, the metal and ligand used, and the size of the acyl chain. Thus charge reduction dominates the ECD spectra of the larger phosphocholine, 16:0/18:1GPCho, but is largely absent in the smaller 6:0/6:0GPCho. For complexes of 16:0/18:1GPCho, n=4-5, fragmentation from the head group mainly occurs via loss of the methyl radical and trimethylamine. At n=3, the relative abundance of fragments due to loss of acyl chain radicals increases. The abundances of ions arising from these radical losses increase further for the n=2 complexes, thereby providing information on the composition and position of the 16:0 and 18:1 acyl groups. Thus ECD of metal complexes provides structurally useful information on the phosphocholine, including the nature of the head group, the acyl chains, and the positions of the acyl chains.     

Polyadenylic acid binding on cationic liposomes doped with the non-ionic nucleolipid Lauroyl Uridine

In this work unilamellar liposomes doped with a novel non-ionic 5′-Uridine-head nucleolipid, Lauroyl Uridine (LU), were prepared and characterized for their ability to interact with the polynucleotide polyadenylic acid (poly-A). Vesicles, were made up of the cationic lipid DOTAP (1,2-Dioleoyl-3-Trimethylammonium-Propane), the zwitterionic lipid DOPE (1,2-Dioleoyl-sn-Glycero-3-Phosphoethanolamine), and the novel amphiphile Lauroyl Uridine. The influence of the non-ionic nucleolipid on essential liposomes properties, such as the structure and net charge was first investigated by a comparative analysis performed on the different lipoplex preparations by means of ζ-potential and size measurements. Both structure and net charge of liposomes were shown to be not modified by the presence of the non-ionic nucleolipid.The role of the synthetic lipid inserted as anchor in the liposome bilayer in the condensation process between vesicles and the polynucleotide poly-A was then analyzed by UV–vis, Circular Dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopies. The data presented comparative UV–vis analyses that evidenced the occurrence of staking interactions in the poly-A only in LU containing lipoplexes. CD and NMR studies indicated the presence of H-bonding interaction between Lauroyl Uridine containing vesicles and the polynucleotide poly-A. The results presented in this work support a role for Lauroyl Uridine in A-U molecular recognition, thus, suggesting that cationic liposomes doped with the non-ionic nucleolipid Lauroyl Uridine could represent a model system to study molecular interactions among single stranded polynucleotides and lipid anchor bearing the complementary bases.     

Metal complexes of tetrapodal ligands: synthesis, spectroscopic and thermal studies, and X-ray crystal structure studies of Na(I), Ca(II), Sr(II), and Ba(II) complexes of tetrapodal ligands N,N,N',N'-tetrakis(2-hydroxypropyl)ethylenediamine and N,N,N',N'-tetrakis(2-hydroxyethyl)ethylenediamine

Twelve complexes 1-12 of general category [M(ligand)(anion)(x)(water)(y)], where ligand = N,N,N',N'-tetrakis(2-hydroxypropyl/ethyl)ethylenediamine (HPEN/HEEN), anion = anions of picric acid (PIC), 3,5-dinitrobenzoic acid (DNB), 2,4-dinitrophenol (DNP), and o-nitrobenzoic acid (ONB), M = Ca(2+), Sr(2+), Ba(2+), or Na(+), x = 1 and 2, and y = 0-4, were synthesized. All of these complexes were characterized by elemental analysis, IR, (1)H and (13)C NMR, and thermal studies. X-ray crystal studies of these complexes 1-12, [Ca(HPEN)(H(2)O)(2)](PIC)(2).H(2)O (1), [Ca(HEEN)(PIC)](PIC) (2), Ba(HPEN)(PIC)(2) (3), [Na(HPEN)(PIC)](2) (4), Ca(HPEN)(H(2)O)(2)](DNB)(2).H(2)O (5),Ca(HEEN)(H(2)O)](DNB)(2).H(2)O (6), [Sr(HPEN)(H(2)O)(3)](DNB)(2) (7), [Ba(HPEN)(H(2)O)(2)](DNB)(2).H(2)O](2) (8), [[Ba(HEEN)(H(2)O)(2)](ONB)(2)](2) (9), [[Sr(HPEN)(H(2)O)(2)](DNP)(2)](2) (10), [[Ba(HPEN)(H(2)O)(2)](DNP)(2)](2) (11), and [Ca(HEEN)(DNP)](DNP) (H(2)O) (12), have been carried out at room temperature. Factors which influence the stability and the type of complex formed have been recognized as H-bonding interactions, presence/absence of solvent, nature of the anion, and nature of the cation. Both the ligands coordinate the metal ion through all the six available donor atoms. The complexes 1 and 5-11 have water molecules in the coordination sphere, and their crystal structures show that water is playing a dual character. It coordinates to the metal ion on one hand and strongly hydrogen bonds to the anion on the other. These strong hydrogen bonds stabilize the anion and decrease the cation-anion interactions by many times to an extent that the anions are completely excluded out of the coordination sphere and produce totally charge-separated complexes. In the absence of water molecules as in 2 and 3 the number of hydrogen bonds is reduced considerably. In both the complexes the anions case interact more strongly with the metal ion to give rise to a partially charge-separated 2 or tightly ion-paired 3 complex. High charge density Ca(2+) forms only monomeric complexes. It has more affinity toward stronger nucleophiles such as DNP and PIC with which it gives partially charge-separated eight-coordinated complexes. But with relatively weaker nucleophile like DNB, water replaces the anion and produces a seven coordinated totally charge-separated complex. Sr(2+) with lesser charge/radius ratio forms only charge-separated monomeric as well as dimeric complexes. Higher coordination number of Sr(2+) is achieved with coordinated water molecules which may be bridging or nonbridging in nature. All charge-separated complexes of the largest Ba(2+) are dimeric with bridging water molecules. Only one monomeric ion-paired complex was obtained with Ba(PIC)(2). Na(+) forms a unique dinuclear cryptand-like complex with HPEN behaving as a heptadentate chelating-cum-bridging ligand.     

Langmuir films of (alpha-amino) phosphorus amphiphiles on various ion-containing subphases

Monolayers of amphiphilic (alpha-amino)phosphonocarboxylic and (alpha-amino)phosphonic acids have been formed by adsorption at the air/water interface. The influence of both the ionic strength and the pH of the subphase on the stability and compactness of the monolayers have been studied. The stability and the compactness of the Langmuir films are enhanced by introduction of metallic ions such as Ca(2+) or Mg(2+) in the subphases. These effects are more pronounced with Ca(2+). These metal ions can form dimeric complexes with the phosphorus moieties of the surfactant polar heads and therefore bring the amphiphiles closer. For the less hydrophobic derivative, complexation with Ca(2+) or Mg(2+) is required to ensure the formation of a stable monomolecular film. For both phosphonocarboxylic and phosphonic compounds, models have been proposed to represent the complexation phenomenon at the air/water interface.     

Relative calcium-binding strengths of amino acids determined using the kinetic method

We have measured the relative calcium-binding energies of amino acids using tandem mass spectrometry of Ca(2+)-bound trimeric amino acids. Although calcium-bound dimeric amino acid complexes coordinated too strongly to allow observation of the two competing dissociation products (calcium-bound monomeric ions) required for analysis of their metal binding affinities using the conventional kinetic method, the Ca(2+)-bound trimeric cluster ions dissociated readily to form dimeric cluster ions through simple ligand losses. The calcium-binding energies were obtained by comparing the ratio of the [Ca(2+)(A(1))(2) - H(+)](+) and [Ca(2+) (A(1))(A(2)) - H(+)](+) ions that dissociated from the [Ca(2+) (A(1))(2)(A(2)) - H(+)](+) ion and the ratio of the [Ca(2+)(A(2))(2) - H(+)](+) and [Ca(2+)(A(1)) (A(2)) - H(+)](+) ions that dissociated from the [Ca(2+)(A(1))(A(2))(2) - H(+)](+) ion, where A(1) and A(2) represent two amino acids. The energies deduced from this analysis represent the relative average binding energies of complexes having the form [Ca(2+)(A(1))(2) - H(+)](+). The relative Ca(2+)-binding strengths of the alpha-amino acid complexes follow the order Cys < Ser < Thr < Ile < Leu < Val < Gly < Ala < Pro < Phe < Met < Tyr < Asn < His < Gln < Trp < Lys < Arg. To our knowledge, this report provides the first example of using kinetic methods to determine the relative binding strengths of divalent metal-amino acid complexes.     

The effect of protein dielectric coefficient on the ionic selectivity of a calcium channel

Calcium-selective ion channels are known to have carboxylate-rich selectivity filters, a common motif that is primarily responsible for their high Ca(2+) affinity. Different Ca(2+) affinities ranging from micromolar (the L-type Ca channel) to millimolar (the ryanodine receptor channel) are closely related to the different physiological functions of these channels. To understand the physical mechanism for this range of affinities given similar amino acids in their selectivity filters, we use grand canonical Monte Carlo simulations to assess the binding of monovalent and divalent ions in the selectivity filter of a model Ca channel. We use a reduced model where the electolyte is modeled by hard-sphere ions embedded in a continuum dielectric solvent, while the interior of protein surrounding the channel is allowed to have a dielectric coefficient different from that of the electrolyte. The induced charges that appear on the protein/lumen interface are calculated by the induced charge computation method [Boda et al., Phys. Rev. E 69, 046702 (2004)]. It is shown that decreasing the dielectric coefficient of the protein attracts more cations into the pore because the protein's carboxyl groups induce negative charges on the dielectric boundary. As the density of the hard-sphere ions increases in the filter, Ca(2+) is absorbed into the filter with higher probability than Na(+) because Ca(2+) provides twice the charge to neutralize the negative charge of the pore (both structural carboxylate oxygens and induced charges) than Na(+) while occupying about the same space (the charge/space competition mechanism). As a result, Ca(2+) affinity is improved an order of magnitude by decreasing the protein dielectric coefficient from 80 to 5. Our results indicate that adjusting the dielectric properties of the protein surrounding the permeation pathway is a possible way for evolution to regulate the Ca(2+) affinity of the common four-carboxylate motif.     

Binding of the two-valence-electron metal ions Sc(+), Ti(2+), and V(3+) to the second-row hydrides BeH(2), BH(3), NH(3), OH(2), and FH: a computational study

We report results from a computational study of the binding in complexes formed from one of the transition-metal ions Sc(+), Ti(2+), or V(3+), each of which has two valence electrons outside an argon core, and one of the second-row hydrides FH, OH(2), NH(3), BH(3), or BeH(2). The complexes that involve the electron-rich ligands FH, OH(2), and NH(3) have strong ion-dipole components to their binding. There are large stabilization energies for sigma-interactions that transfer charge from occupied lone-pair natural bond orbitals on the F, O, or N atom of the (idealized) Lewis structure into empty non-Lewis orbitals on the metal ions; these interactions effectively increase electron density in the bonding region between the metal ion and liganded atom, and the metal ions in these complexes act in the capacity of Lewis acids. The complexes formed from the electron-poor hydrides BH(3) and BeH(2) consistently incorporate bridging hydrogen atoms to support binding, and there are large stabilization energies for interactions that transfer charge from the Be-H or B-H bonds into the region between the metal ion and liganded atom. The metal ions in Sc(+)-BeH(2), Ti(2+)-BeH(2), Ti(2+)-BH(3), and V(3+)-BH(3) act in the capacity of Lewis acids, whereas the scandium ion in Sc(+)-BH(3) acts as a Lewis base.     

Photoinduced Electron Transfer in Pentaammineruthenium(II) Complexes of 1-(4-Cyanophenyl)imidazole

A new bridging ligand, 1-(4-cyanophenyl)imidazole (CPI) has been prepared, as well as its N-methylated derivative 1-methyl-3-(4-cyanophenyl)imidazolium iodide (CPI-Me(+)I(-)). The mononuclear and binuclear complexes [(NH(3))(5)Ru-CPI-Me](3+) and [(NH(3))(5)Ru-CPI-Ru(NH(3))(5)](4+) have been obtained. Free CPI is planar, according to theoretical calculations (MMX and MNDO), and its luminescence properties suggest the occurence of a twisted internal charge transfer (TICT) state. The comparison of the two ruthenium complexes reveals the spectral and electrochemical features of coordination by the cyanophenyl or by the imidazole groups. Controlled oxidation of the binuclear complex [(NH(3))(5)Ru-CPI-Ru(NH(3))(5)](4+) yields the mixed valence species [(NH(3))(5)Ru-CPI-Ru(NH(3))(5)](5+) in which the ruthenium coordinated to the cyanophenyl group is ruthenium(II) while the ruthenium linked to imidazole is ruthenium(III). An intervalence band is observed at 640 nm (epsilon = 188), from which the effective metal-metal coupling through the bridging ligand is determined as 0.032 eV. This value is satisfactorily reproduced by a theoretical calculation using the effective Hamiltonian theory. Finally the binuclear complex exhibits a weak luminescence when excited either on the ligand band near 260 nm or on the metal-to-ligand charge transfer band near 410 nm. The CPI ligand is the first example of a TICT-forming species with appreciable coupling between metallic sites and can be considered as a first step toward a molecular switch.     

Effect of divalent cations on DMPC/DHPC bicelle formation and alignment

Many important classes of biomolecules require divalent cations for optimal activity, making these ions essential for biologically relevant structural studies. Bicelle mixtures composed of short-chain and long-chain lipids are often used in solution- and solid-state NMR structure determination; however, the phase diagrams of these useful orienting media and membrane mimetics are sensitive to other solution components. Therefore, we have investigated the effect of varying concentrations of four divalent cations, Ca(2+), Mg(2+), Zn(2+), and Cd(2+), on cholesterol sulfate-stabilized DMPC/DHPC bicelles. We found that low concentrations of all the divalent ions are tolerated with minimal perturbation. At higher concentrations Zn(2+) and Cd(2+) disrupt the magnetically aligned phase while Ca(2+) and Mg(2+) produce more strongly oriented phases. This result indicates that divalent cations are not only required to maintain the biological activity of proteins and nucleic acids; they may also be used to manipulate the behavior of the magnetically aligned phase.     

Facile synthesis and relaxation properties of novel bispolyazamacrocyclic Gd3+ complexes: an attempt towards calcium-sensitive MRI contrast agents

Three novel GdDO3A-type bismacrocyclic complexes, conjugated to Ca (2+) chelating moieties like ethylenediaminetetraacetic acid and diethylenetriamine pentaacetic acid bisamides, were synthesized as potential "smart" magnetic resonance imaging contrast agents. Their sensitivity toward Ca (2+) was studied by relaxometric titrations. A maximum relaxivity increase of 15, 6, and 32% was observed upon Ca (2+) binding for Gd 2L (1), Gd 2L (2), and Gd 2L (3), respectively (L (1) = N, N-bis{1-[{[({1-[1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-10-yl]eth-2-yl}amino)carbonyl]methyl}-(carboxymethyl)amino]eth-2-yl}aminoacetic acid; L (2) = N, N-bis[1-({[({alpha-[1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-10-yl]- p-tolylamino}carbonyl)methyl]-(carboxymethyl)}amino)eth-2-yl]aminoacetic acid; L (3) = 1,2-bis[{[({1-[1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-10-yl]eth-2-yl}amino)carbonyl]methyl}(carboxymethyl)amino]ethane). The apparent association constants are log K A = 3.6 +/- 0.1 for Gd 2L (1) and log K A = 3.4 +/- 0.1 for Gd 2L (3). For the interaction between Mg (2+) and Gd 2L (1), log K A = 2.7 +/- 0.1 has been determined, while no relaxivity change was detected with Gd 2L (3). Luminescence lifetime measurements on the Eu (3+) complexes in the absence of Ca (2+) gave hydration numbers of q = 0.9 (Eu 2L (1)), 0.7 (Eu 2L (2)), and 1.3 (Eu 2L (3)). The parameters influencing proton relaxivity of the Gd (3+) complexes were assessed by a combined nuclear magnetic relaxation dispersion (NMRD) and (17)O NMR study. Water exchange is relatively slow on Gd 2L (1) and Gd 2L (2) ( k ex (298) = 0.5 and 0.8 x 10 (6) s (-1)), while it is faster on Gd 2L (3) (k ex (298) = 80 x 10 (6) s (-1)); in any case, it is not sensitive to the presence of Ca (2+). The rotational correlation time, tau R (298), differs for the three complexes and reflects their rigidity. Due to the benzene linker, the Gd 2L (2) complex is remarkably rigid, with a correspondingly high relaxivity despite the low hydration number ( r 1 = 10.2 mM (-1)s (-1) at 60 MHz, 298 K). On the basis of all available experimental data from luminescence, (17)O NMR, and NMRD studies on the Eu (3+) and Gd (3+) complexes of L (1) and L (3) in the absence and in the presence of Ca (2+), we conclude that the relaxivity increase observed upon Ca (2+) addition can be mainly ascribed to the increase in the hydration number, and, to a smaller extent, to the Ca (2+)-induced rigidification of the complex.     

Ru(II) electron transfer systems containing S-donor ligands

The synthesis and properties of 3 new ligand-bridged bimetallic complexes, 1(2+), 2(2+), and 3(2+), containing [RuCl([9]aneS(3))](+) metal centers are reported. Each complex was bridged by a different ditopic ligand. 1(2+) is bridged by 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine (bptz), while 2(2+) and 3(2+) are bridged by 2,3-bis(2-pyridyl)pyrazine (dpp) and 2,2'-bipyrimidine (bpym), respectively. The Ru([II]) isovalent states of these complexes have been investigated using a variety of techniques. In the case of 3(2+), X-ray crystallography studies show preferential crystallization of an anti form with respect to coordinated chloride ligands (crystal data for [3][Cl(2)].4H(2)O: C(20)H(38)Cl(4)N(4)O(4)Ru(2)S(6), monoclinic, space group P2(1)/a, a = 10.929(14), b = 13.514(17), c = 11.299(16) A, beta = 90.52(1), V = 1669 A(3), Z = 2). UV/vis spectroscopy shows that spectra of these complexes are dominated by intraligand (pi-->pi) and metal-to-ligand Ru(d)-->L(pi) charge transfer transitions. Electrochemical studies reveal that metal-metal interactions are sufficiently intense to generate the Ru(III)/Ru(II) mixed valence [[RuCl([9]aneS(3))(2)](L-L)](3+) state, where L-L = individual bridging ligands. Although the 1(3+), 2(3+), and 3(3+) mixed valence states were EPR silent at room temperature and 77 K, isotropic solution spectra were observed for the electrochemically generated radical cations 1(+), 2(+), and 3(+), with 1(+) displaying well-resolved hyperfine coupling to bridging ligand nitrogens. Using UV/vis/NIR spectroelectrochemistry, we investigated optical properties of the mixed valence complexes. All three showed intervalence charge transfer (IVCT) bands that are much more intense than electrochemical data indicate. Indeed, a comparison of IVCT data for 1(3+) with an analogous structure containing [(NH3)(3)Ru](2+) metal centers shows that the IVCT in the new complex is an order of magnitude more intense. It is concluded that although the new complexes show relatively weak electrostatic interactions, they possess large resonance energies.     

A new family of Ru(II) polypyridyl complexes containing open-chain crown ether for Mg2+ and Ca2+ probing

Six polypyridyl bridging ligands BL(1-6) containing open-chain crown ether, where BL(1-3) formed by the condensation of 4,5-diazafluoren-9-hydrazine with 1,7-bis-(4-formylphenyl)-1,4,7-trioxaheptane, 1,10-bis-(4-formylphenyl)-1,4,7,10-tetraoxadecane, and 1,13-bis-(4-formylphenyl)-1,4,7,10,13-pentaoxatridecane, respectively, BL(4-6) formed by the reaction of 9-(4-hydroxy)phenylimino-4,5-diazafluorene with diethylene glycol di-p-tosylate, triethylene glycol di-p-tosylate, and tetraethylene glycol di-p-tosylate, respectively, have been synthesized. Reaction of Ru(bpy)(2)Cl(2).2H(2)O with BL(1-6), respectively, afforded six bimetallic complexes [(bpy)(2)RuBL(1-6)Ru(bpy)(2)](4+) as PF(6)(-) salts. Cyclic voltammetry of these complexes is consistent with one Ru(II)-centered oxidation around 1.32V and three ligand-centered reductions. These complexes show metal-to-ligand charge transfer absorption at 413-444 nm and emission at 570 nm. Binding behavior of complexes with alkali and alkaline-earth metal ions are investigated by UV-vis absorption, fluorescence, and cyclic voltammetry. Addition of alkali and alkaline-earth metal ions to the solution of [(bpy)(2)RuBL(1-6)Ru(bpy)(2)](PF(6))(4) all result in a progressive quenching of fluorescence, a hyperchromic effect of UV-vis absorption, and a progressive cathodal shift of Ru(II)-centered E(1/2). Ru-BL(2) and Ru-BL(5) show the highest binding ability toward Mg(2+) among the five cations examined while Ru-BL(3) and Ru-BL(6) exhibit good selective recognition ability to Ca(2+).