Equilibrium, 1H and 13C NMR spectroscopy,and X-ray diffraction studies on the complexes Bi(DOTA)- and Bi(DO3A-Bu)

Several Bi(III) complexes are used in medicine as drugs. Bi(DO3A-Bu) has recently been proposed as a nonionic contrast agent in X-ray imaging (H(3)DO3A-Bu = 10-[2,3-dihydroxy-(1-hydroxymethyl)propyl]-1,4,7,10-tetraazacyclododecane-1,4,7,-triacetic acid). The solution equilibria and NMR structure and dynamics of Bi(DO3A-Bu) and of the similar Bi(DOTA)(-) have been investigated (H(4)DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The stability constants were determined with the study of the competition equilibria between Br(-) ions and the ligands DOTA or DO3A-Bu for the Bi(III) by spectrophotometry. The stability constants, obtained for Bi(DOTA)(-) and Bi(DO3A-Bu), are very high, log K = 30.3 and 26.8, respectively. Potentiometric titrations indicated the dissociation of one of the protons among the three alcoholic OH groups in Bi(DO3A-Bu). The dissociation constant is log K = 7.53 (0.09) indicating that at physiological pH about 50% of the species possess -1 charge. It was shown by (1)H and (13)C NMR spectroscopy that the OH group attached to the middle carbon atom of the "butriol" side chain is coordinated to the Bi(III) and starts to deprotonate at pH > 5.5. The crystal structure of NaBi(DOTA).H(2)O shows an octacoordinated arrangement of the donor atoms around the Bi(III), with no water in the inner sphere. The crystals belong to the centrosymmetric space group C2/c. The temperature dependent (1)H and (13)C NMR spectra indicate that both Bi(DOTA)(-) and Bi(DO3A-Bu)(-) complexes are fluxional. For Bi(DOTA), the Delta(deltadeltadeltadelta) right harpoon over left harpoon Lambda(lambdalambdalambdalambda) fluxionality was identified, and on the basis of the activation parameters, a synchronous motion was suggested for the fluxional motion resulting in the change of ring conformation and of the helicity of the complex. The transition state is supposed to be more symmetrical than the initial state. The deprotonated Bi(DO3A-Bu) has a highly asymmetric NMR structure in solution, and its fluxional motion is slower than that of Bi(DOTA)(-).     

Revealing the mechanisms behind SnO2 nanoparticle formation and growth during hydrothermal synthesis: an in situ total scattering study

The formation and growth mechanisms in the hydrothermal synthesis of SnO(2) nanoparticles from aqueous solutions of SnCl(4)·5H(2)O have been elucidated by means of in situ X-ray total scattering (PDF) measurements. The analysis of the data reveals that when the tin(IV) chloride precursor is dissolved, chloride ions and water coordinate octahedrally to tin(IV), forming aquachlorotin(IV) complexes of the form [SnCl(x)(H(2)O)(6-x)]((4-x)+) as well as hexaaquatin(IV) complexes [Sn(H(2)O)(6-y)(OH)(y)]((4-y)+). Upon heating, ellipsoidal SnO(2) nanoparticles are formed uniquely from hexaaquatin(IV). The nanoparticle size and morphology (aspect ratio) are dependent on both the reaction temperature and the precursor concentration, and particles as small as ~2 nm can be synthesized. Analysis of the growth curves shows that Ostwald ripening only takes place above 200 °C, and in general the growth is limited by diffusion of precursor species to the growing particle. The c-parameter in the tetragonal lattice is observed to expand up to 0.5% for particle sizes down to 2-3 nm as compared to the bulk value. SnO(2) nanoparticles below 3-4 nm do not form in the bulk rutile structure, but as an orthorhombic structural modification, which previously has only been reported at pressures above 5 GPa. Thus, adjustment of the synthesis temperature and precursor concentration not only allows control over nanoparticle size and morphology but also the structure.     

Synthesis, potentiometric, kinetic, and NMR Studies of 1,4,7,10-tetraazacyclododecane-1,7-bis(acetic acid)-4,10-bis(methylenephosphonic acid) (DO2A2P) and its complexes with Ca(II), Cu(II), Zn(II) and lanthanide(III) ions

A cyclen-based ligand containing trans-acetate and trans-methylenephosphonate pendant groups, H 6DO2A2P, was synthesized and its protonation constants (12.6, 11.43, 5.95, 6.15, 2.88, and 2.77) were determined by pH-potentiometry and (1)H NMR spectroscopy. The first two protonations were shown to occur at the two macrocyclic ring N-CH 2-PO 3 (2-) nitrogens while the third and fourth protonations occur at the two phosphonate groups. In parallel with protonation of the two -PO 3 (2-) groups, the protons from the NH (+)-CH 2-PO 3 (2-) are transferred to the N-CH 2-COO (-) nitrogens. The stability constants of the Ca (2+), Cu (2+), and Zn (2+) (ML, MHL, MH 2L, and M 2L) complexes were determined by direct pH-potentiometry. Lanthanide(III) ions (Ln (3+)) form similar species, but the formation of complexes is slow; so, "out-of-cell" pH-potentiometry (La (3+), Eu (3+), Gd (3+), Y (3+)) and competitive spectrophotometry with Cu(II) ion (Lu (3+)) were used to determine the stability constants. By comparing the log K ML values with those of the corresponding DOTA (H 4DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and DOTP (H 8DOTP = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonic acid) complexes, the order DOTA < DO2A2P < DOTP was found for all the metal ion complexes examined here with the exception of the Ca (2+) complexes, for which the order is reversed. The relaxivity of Gd(DO2A2P) decreases between pH 2 and 7 but remains constant in the pH range of 7 < pH < 12 ( r 1 = 3.6 mM (-1) s (-1)). The linewiths of the (17)O NMR signals of water in the absence and presence of Gd(DO2A2P) (at pH = 3.45 and 8.5) between 274 and 350 K are practically the same, characteristic of a q = 0 complex. Detailed kinetic studies of the Ce (3+) and Gd (3+) complexes with DO2A2P showed that complex formation is slow and involves a high stability diprotonated intermediate Ln(H 2DO2A2P)*. Rearrangement of the diprotonated intermediate into the final complex is an OH (-) assisted process but, unlike formation of Ln(DOTA) complexes, rearrangement of Ln(H 2DO2A2P)* also takes place spontaneously likely as a result of transfer of one of the protons from a ring nitrogen to a phosphonate group. The order of the OH (-) assisted formation rates of complexes is DOTA > DO2A2P > DOTP while the order of the proton assisted dissociation rates of the Gd (3+) complexes is reversed, DOTP > DO2A2P > DOTA. (1)H and (13)C NMR spectra of Eu(DO2A2P) and Lu(DO2A2P) were assigned using two-dimensional correlation spectroscopy (2D COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear chemical shift correlation (HETCOR), and exchange spectroscopy (EXSY) NMR methods. Two sets of (1)H NMR signals were observed for Eu(DO2A2P) characteristic of the presence of two coordination isomers in solution, a twisted square antiprism (TSAP) and a square antiprism (SAP), in the ratio of ~93% and ~7%, respectively. Line shape analysis of the (1)H NMR spectra of Lu(DO2A2P) gave lower activation parameters compared to La(DOTP) for interconversion between coordination isomers. This indicates that the Ln(DO2A2P) complexes are less rigid probably due to the different size and spatial requirements of the carboxylate and phosphonate groups.     

Formation kinetics and stability studies on the lanthanide complexes of 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid by capillary electrophoresis

In this study, the kinetic behaviors of four lanthanide ions, Sm(3+), Dy(3+), Yb(3+) and Lu(3+), when mixed with a polyazamacrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA), were investigated by capillary electrophoresis (CE) in the pH range of 2.0-6.0. At pH 2.0, the formation rate of DOTA-metal complex is extremely low as very little complex was detected after 5 days reaction, whereas almost no free DOTA was found in the mixture of metal ion and DOTA after 4 min at pH 6.0. The second-order kinetic association rate constants of the four lanthanide ions chelates at pH 4.2 were calculated as 1.44 x 10(-2) mM(-1)min(-1), 5.20 x 10(-2) mM(-1)min(-1), 4.56 x 10(-2) mM(-1)min(-1) and 4.54 x 10(-2) mM(-1)min(-1) at 25 degrees C with CE, respectively. In addition, the stability constants of the four lanthanide ions with DOTA were determined by CE at pH 3.0 where approximately 80-90% of the metal ions were associated with DOTA at 25 degrees C. The measured stability constants (log K(f)) of the four DOTA-metal complexes were 23.36, 23.93, 23.39 and 23.06, respectively, and correlated well with published data obtained by different methods. The percentage of metal ion bound with DOTA was evaluated as a function of reactant concentration in pH 6.0 buffer. After adding excess strong acid (0.1 M HCl) to each solution of DOTA-metal was formed at pH 6.0, no released DOTA was detected after 24 h; thus, dissociation of these lanthanide complexes did not occur under strongly acidic conditions. The Ln(DOTA)(-) species for the four DOTA-metal complexes were characterized by electrospray ionization-mass spectroscopy (ESI-MS), and the results correlated with proposed structures.     

Novel macrocyclic EuII complexes: fast water exchange related to an extreme M-O water distance

Eu(II) complexes are potential candidates for pO(2)-responsive contrast agents in magnetic resonance imaging. In this regard, we have characterized two novel macrocyclic Eu(II) chelates, [Eu(II)(DOTA)(H(2)O)](2-) and [Eu(II)(TETA)](2-) (H(4)DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, H(4)TETA=1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid) in terms of redox and thermodynamic complex stability, proton relaxivity, water exchange, rotation and electron spin relaxation. Additionally, solid-state structures were determined for the Sr(II) analogues. They revealed no inner-sphere water in the TETA and one inner-sphere water molecule in the DOTA complex. This hydration pattern is retained in solution, as the (17)O chemical shifts and (1)H relaxation rates proved for the corresponding Eu(II) compounds. The thermodynamic complex stability, determined from the formal redox potential and by pH potentiometry, of [Eu(II)(DOTA)(H(2)O)](2-) (lg K(Eu(II))=16.75) is the highest among all known Eu(II) complexes, whereas the redox stabilities of both [Eu(II)(DOTA)(H(2)O)](2-) and [Eu(II)(TETA)](2-) are inferior to that of 18-membered macrocyclic Eu(II) chelates. Variable-temperature (17)O NMR, NMRD and EPR studies yielded the rates of water exchange, rotation and electron spin relaxation. Water exchange on [Eu(II)(DOTA)(H(2)O)](2-) is remarkably fast (k298(ex)=2.5 x 10(9) s(-1)). The near zero activation volume (DeltaV++ =+0.1+/-1.0 cm(3) mol(-1)), determined by variable-pressure (17)O NMR spectroscopy, points to an interchange mechanism. The fast water exchange can be related to the low charge density on Eu(II), to an unexpectedly long M-O(water) distance (2.85 A) and to the consequent interchange mechanism. Electron spin relaxation is considerably slower on [Eu(II)(DOTA)(H(2)O)](2-) than on the linear [Eu(II)(DTPA)(H(2)O)](3-) (H(5)DTPA=diethylenetriaminepentaacetic acid), and this difference is responsible for its 25 percent higher proton relaxivity (r(1)=4.32 mM(-1) s(-1) for [Eu(II)(DOTA)(H(2)O)](2-) versus 3.49 mM(-1) s(-1) for [Eu(II)(DTPA)(H(2)O)](3-); 20 MHz, 298 K).     

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.     

Complex formation of vanadium(IV) with 1,3,5-triamino-1,3,5-trideoxy-cis-inositol and related ligands

The complex formation of vanadium(IV) with 1,3,5-triamino-1,3,5-trideoxy-cis-inositol (taci) and 1,3,5-trideoxy-1,3,5-tris(dimethylamino)-cis-inositol (tdci) was studied in aqueous solution and in the solid state. The formation constants of [V(IV)O(taci)](2+), [V(IV)O(tdci)](2+), and [V(IV)(tdci)(2)](4+) and of the deprotonation product [V(IV)(tdci)(2)H(-)(1)](3+) were determined (25 degrees C, 0.1 M KNO(3)). Cyclic voltammetry measurements established a reversible one-electron transfer for the [V(IV)(tdci)(2)H(-)(m)]((4)(-)(m))/[V(III)(tdci)(2)H(-)(n)]((3)(-)(n)) couple (0 相似文献   

NMR and EPR structural delineation of copper(II) complexes formed by kanamycin A in water

The complexes formed by kanamycin A at three different pH values (5.5, 7.4 and 12.0) were investigated by NMR and EPR spectroscopy. Paramagnetic relaxation contributions to proton relaxation rates were measured using a combination of the TOCSY sequence with the inversion recovery experiment in order to gain signal resolution in the bulk region. Measured contributions were converted into distances and used for structural determination by restrained simulated annealing where all possible chair and boat conformations of the rings were taken into account. The interaction of the Cu(II) ion with the nitrogen of the C ring is apparent at all pH values. At higher pH also the amino group of ring A starts to be involved in the metal coordination sphere. This is accompanied by a switch in conformation of ring C. Structures are consistent with the involvement in the coordination sphere either of the 2' or 4' hydroxyl oxygens at pH 5.5 and the 5 and the 6' hydroxyl oxygens (or the ring oxygen) at pH 12.0.     

Molecular understanding of the formation of surface zirconium hydrides upon thermal treatment under hydrogen of [([triple bond]SiO)Zr(CH2tBu)3] by using advanced solid-state NMR techniques

The reaction of [([triple bond]SiO)Zr(CH(2)tBu)(3)] with H(2) at 150 degrees C leads to the hydrogenolysis of the zirconium-carbon bonds to form a very reactive hydride intermediate(s), which further reacts with the surrounding siloxane ligands present at the surface of this support to form mainly two different zirconium hydrides: [([triple bond]SiO)(3)Zr-H] (1a, 70-80%) and [([triple bond]SiO)(2)ZrH(2)] (1b, 20-30%) along with silicon hydrides, [([triple bond]SiO)(3)SiH] and [([triple bond]SiO)(2)SiH(2)]. Their structural identities were identified by (1)H DQ solid-state NMR spectroscopy as well as reactivity studies. These two species react with CO(2) and N(2)O to give, respectively, the corresponding formate [([triple bond]SiO)(4-x)Zr(O-C(=O)H)(x)] (2) and hydroxide complexes [([triple bond]SiO)(4-x)Zr(OH)(x)] (x = 1 or 2 for 3a and 3b, respectively) as major surface complexes.     

Coordination features of a terpyridine-containing polyamine receptor. Effect of protonation on the photophysical properties of the complexes

The synthesis of the new terpyridine-containing macrocycle 2,6,10,14-tetraaza[15](6,6')cyclo(2,2':6',2')terpyridinophane (L) is reported. The ligand contains a tetraamine chain linking the 6,6' positions of a terpyridine unit. A potentiometric, (1)H NMR, UV-vis spectrophotometric and fluorescence emission study on the basicity properties of in aqueous solutions shows that the first four protonation steps occur on the polyamine chain, while the terpyridine nitrogens are involved in proton binding only in the last protonation step at strongly acidic pH values. Cu(II), Zn(II), Cd(II) and Pb(II) complexation was studied in aqueous solution by means of potentiometric, spectrophotometric and spectrofluorimetric measurements. Cu(II) and Zn(II) can form both mono- and dinuclear complexes in solution, while the larger Cd(II) and Pb(II) give only mononuclear complexes. In the [ML](2+) complexes (M = Zn(II) or Cd(II)) the metal is unequivocally bound to the terpyridine unit. Some amine groups are not coordinated and can quench the fluorescence emission of the terpyridine unit thanks to an electron transfer process. Protonation of the unbound amine groups inhibits the eT process, affording fluorescent [MLH(x)]((2+x)+) complexes.     

NMR studies of coupled low- and high-barrier hydrogen bonds in pyridoxal-5'-phosphate model systems in polar solution

The 1H and 15N NMR spectra of several 15N-labeled pyridoxal-5'-phosphate model systems have been measured at low temperature in various aprotic and protic solvents of different polarity, i.e., dichloromethane-d2, acetonitrile-d3, tetrahydrofuran-d8, freon mixture CDF3/CDClF2, and methanol. In particular, the 15N-labeled 5'-triisopropyl-silyl ether of N-(pyridoxylidene)-tolylamine (1a), N-(pyridoxylidene)-methylamine (2a), and the Schiff base with 15N-2-methylaspartic acid (3a) and their complexes with proton donors such as triphenylmethanol, phenol, and carboxylic acids of increasing strength were studied. With the use of hydrogen bond correlation techniques, the 1H/15N chemical shift and scalar coupling data could be associated with the geometries of the intermolecular O1H1N1 (pyridine nitrogen) and the intramolecular O2H2N2 (Schiff base) hydrogen bonds. Whereas O1H1N1 is characterized by a series of asymmetric low-barrier hydrogen bonds, the proton in O2H2N2 faces a barrier for proton transfer of medium height. When the substituent on the Schiff base nitrogen is an aromatic ring, the shift of the proton in O1H1N1 from oxygen to nitrogen has little effect on the position of the proton in the O2H2N2 hydrogen bond. By contrast, when the substituent on the Schiff base nitrogen is a methyl group, a proton shift from O to N in O1H1N1 drives the tautomeric equilibrium in O2H2N2 from the neutral O2-H2...N2 to the zwitterionic O2-...H2-N(2+) form. This coupling is lost in aqueous solution where the intramolecular O2H2N2 hydrogen bond is broken by solute-solvent interactions. However, in methanol, which mimics hydrogen bonds to the Schiff base in the enzyme active site, the coupling is preserved. Therefore, the reactivity of Schiff base intermediates in pyridoxal-5'-phosphate enzymes can likely be tuned to the requirements of the reaction being catalyzed by differential protonation of the pyridine nitrogen.     

Ternary complexes between cationic GdIII chelates and anionic metabolites in aqueous solution: an NMR relaxometric study

The (1)H and (17)O NMR relaxometric properties of two cationic complexes formed by Gd(III) with a macrocyclic heptadentate triamide ligand, L(1), and its Nmethylated analogue, L(2), have been investigated in aqueous media as a function of pH, temperature and magnetic field strength. The complexes possess two water molecules in their inner coordination sphere for which the rate of exchange has been found to be sensibly faster for the Nmethylated derivative and explained in terms of electronic effects (decrease of the charge density at the metal center) and perturbation of the network of hydrogen-bonded water molecules in the outer hydration sphere. The proton relaxivity shows a marked dependence from pH and decreases of about six units in the pH range 6.5 to 9.0. This has been accounted for by the displacement of the two water molecules by dissolved carbonate which acts as a chelating anion. The formation of ternary complexes with lactate, malonate, citrate, acetate, fluoride and hydrogenphosphate has been monitored by (1)H NMR relaxometric titrations at 20 MHz and pH 6.3 and the value of the affinity constant, K, and of the relaxivity of the adducts could be obtained. Lactate, malonate and citrate interact strongly with the complexes (log K > or =3.7) and coordinate in a bidendate mode by displacing both water molecules. Larger affinity constants have been measured for GdL(2). Acetate, fluoride and hydrogenphosphate form monoaqua ternary complexes which were investigated in detail with regard to their relaxometric properties. The NMR dispersion (NMRD) profiles indicate a large contribution to the relaxivity of the adducts from water molecules belonging to the second hydration shell of the complexes and hydrogen-bonded to the anion. A VT (17)O NMR study has shown a marked increase of the rate of water exchange upon binding which is explained by coordination of the anion in an equatorial site, thus leaving the water molecule in an apical position, more accessible for interactions with the solvent molecules of the second hydration shell which facilitate the exchange process.     

17O NMR and computational study of a tetrasiliconiobate ion, [H(2+x)Si4Nb16O56](14-x)-

Rates of oxygen-isotope exchange were measured in the tetrasiliconiobate ion [H(2+x)Si(4)Nb(16)O(56)]((14-x)-) to better understand how large oxide ions interact with water. The molecule has 19 nonequivalent oxygen sites and is sufficiently complex to evaluate hypotheses derived from our previous work on smaller clusters. We want to examine the extent to which individual oxygen atoms react independently with particular attention given to the order of protonation of the various oxygen sites as the pH decreases from 13 to 6. As in our previous work, we find that the set of oxygen sites reacts at rates that vary over approximately 10(4) across the molecule at 6相似文献   

1H NMR spectroscopic study of complexation of citalopram with beta-cyclodextrin in aqueous solution

(1)H NMR spectroscopic study of citalopram (CT) in the absence as well as in the presence of beta-cyclodextrin (beta-CD) in aqueous solution revealed the formation of four 1:1 beta-CD-CT inclusion complexes. The stoichiometry of the complexes was determined by the continuous variation (Job) method, which was further confirmed by Scott's method. The binding constants (K(R) and K(R, S)) were calculated using Scott's method. The structures of all the complexes have been proposed as shown in the diagrams. All the CT proton resonances showed splitting in the presence of beta-CD, owing to chiral discrimination by the beta-CD, between the two enantiomers. The chiral discrimination appears to be due to different modes of binding of the R- and S-CT in the complexes involving a CN-containing aromatic ring.     

First total H+/Li+ ion exchange in garnet-type Li5La3Nb2O12 using organic acids and studies on the effect of Li stuffing

Garnet-type Li(5+x)Ba(x)La(3-x)Nb(2)O(12) (x = 0, 0.5, 1) was prepared using a ceramic method, and H(+)/Li(+) ion exchange was performed at room temperature using organic acids, such as CH(3)COOH and C(6)H(5)COOH, as proton sources. Thermogravimetric analysis showed that H(+)/Li(+) ion exchange was nearly (100%) completed using the x = 0 member with CH(3)COOH, while it proceeded to about 40% for x = 0.5 and 13% for x = 1. In C(6)H(5)COOH, proton exchange proceeded to about 82% for x = 0, ～40% for x = 0.5, and ～25% for x = 1. Similar proton-exchange trends were reported in H(2)O, where ion exchange occurs more readily for garnets with lower Li content in Li(5+x)Ba(x)La(3-x)Nb(2)O(12), that is, when excess Li ions preferentially reside in the tetrahedral sites of the garnet structure.     

Behaviors of nitrato complexes of nitrosylruthenium in aqueous solutions (author's transl)

Nitrato nitrosylruthenium complexes [RuNO(NO3)x(H2O)5-x] (3-x)+ readily dissociate in aqueous solutions with decrease in pH and increase in electrical conductivity of the solutions. This study aimed to elucidate the behaviours of dissociation of the complexes with time. The change in the amount of undissociated complexes was determined with time. The results indicated that the dissociation was a multi-order reaction involving both protolysis and hydrolysis. The protolysis completed in relatively short period within(several tens of minutes), but it depended on the concentration of the complexes in the solution. The completion of the protolysis and the formation of the resulting dissociation products were observed by absorption spectrometry. The dissociation products, which were assumed as aquohydroxy complexes, underwent the successive step-wise dissociation for a prolonged period as revealed by pH measurements. The rate constants involved in the step-wise dissociation, process were obtained. The degree of dissociation and dissociation constant of the complexes were measured by conductometry.     

Coupling of functional hydrogen bonds in pyridoxal-5'-phosphate-enzyme model systems observed by solid-state NMR spectroscopy

We present a novel series of hydrogen-bonded, polycrystalline 1:1 complexes of Schiff base models of the cofactor pyridoxal-5'-phosphate (PLP) with carboxylic acids that mimic the cofactor in a variety of enzyme active sites. These systems contain an intramolecular OHN hydrogen bond characterized by a fast proton tautomerism as well as a strong intermolecular OHN hydrogen bond between the pyridine ring of the cofactor and the carboxylic acid. In particular, the aldenamine and aldimine Schiff bases N-(pyridoxylidene)tolylamine and N-(pyridoxylidene)methylamine, as well as their adducts, were synthesized and studied using 15N CP and 1H NMR techniques under static and/or MAS conditions. The geometries of the hydrogen bonds were obtained from X-ray structures, 1H and 15N chemical shift correlations, secondary H/D isotope effects on the 15N chemical shifts, or directly by measuring the dipolar 2H-15N couplings of static samples of the deuterated compounds. An interesting coupling of the two "functional" OHN hydrogen bonds was observed. When the Schiff base nitrogen atoms of the adducts carry an aliphatic substituent such as in the internal and external aldimines of PLP in the enzymatic environment, protonation of the ring nitrogen shifts the proton in the intramolecular OHN hydrogen bond from the oxygen to the Schiff base nitrogen. This effect, which increases the positive charge on the nitrogen atom, has been discussed as a prerequisite for cofactor activity. This coupled proton transfer does not occur if the Schiff base nitrogen atom carries an aromatic substituent.     

Binding of an acetic acid ligand to adenosine: a low-temperature NMR study

Binding of an acetic acid (HAc) ligand to adenosine (A) was studied by (1)H NMR spectroscopic techniques. Using a low-melting deuterated Freon mixture as solvent, liquid-state measurements could be performed in the slow exchange regime and allowed a detailed characterization of the formed associates. Thus, at 128 K, trimolecular complexes A.HAc(2) and A(2).HAc with both Watson-Crick and Hoogsteen sites of the central adenine base occupied coexist in various amounts depending on the adenosine:acetic acid molar ratio. Whereas the carboxylic acid OH proton is located closer to the acid for all hydrogen bonds formed, a more deshielded proton at the Watson-Crick site is evidence for a stronger hydrogen bond as compared to the Hoogsteen interaction. For the binding of acetic acid to an adenosine-thymidine base pair in either a Watson-Crick or a Hoogsteen configuration, hydrogen bonds to the available adenine binding site are strengthened as compared to the corresponding hydrogen bonds in the A.HAc(2) complex.     

Chelators for radioimmunotherapy: I. NMR and ab initio calculation studies on 1,4,7,10-tetra(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO4Pr) and 1,4,7-tris(carboxymethyl)-10-(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO3A1Pr)

This work describes the modification of the chelating agent 1,4,7,10-tetraazacyclododecane-N,N',N' ',N' "-tetraacetic acid (DOTA) to improve the rate of metal loading for radioimmunotherapy applications. Previous ab initio calculations predicted that the compounds 1,4,7,10-tetra(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO4Pr) and 1,4,7-tris(carboxymethyl)-10-(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO3A1Pr) have a ca. 2000-fold improvement in yttrium metal loading rates compared to those of DOTA (Jang, Y. H.; Blanco, M.; Dasgupta, S.; Keire, D. A.; Shively, J. E.; Goddard, W. A., III. J. Am. Chem. Soc. 1999, 121, 6142-6151). In this study, we report the synthesis, purification, (1)H-NMR chemical shift assignments, pK(a) values, metal loading rate measurements, and additional ab initio calculations of these two compounds. The yttrium loading rates of DO3A1Pr are approximately twice those of DOTA, at pH 4.6 and 37 degrees C. The NMR data indicates that the DO4Pr analogue forms a stable type I complex but does not form a type II complex. The new ab initio calculations performed on DO4Pr and DO3A1Pr indicate that the rate-determining step is the deprotonation of the first macrocycle amine proton, not the second proton as assumed in the previous calculations. The new calculations predict an improvement in the rate of metal loading that more closely matches the experimentally observed change in the rate.     

Intrinsic surface reaction equilibrium constants of structurally charged amphoteric hydrotalcite-like compounds

The relative equations among intrinsic surface reaction equilibrium constants (K in 1-pK model, K(a1)(int) and K(a2)(int) in 2-pK model, and *K(Na)(int) and *K(Cl)(int) in inert electrolyte chemical binding model), points of zero charge (PZC), and structural charge density (sigma(st)) for amphoteric solids with structural charge were established to investigate the effects of sigma(st) on intrinsic equilibrium constants and PZC. The intrinsic equilibrium constants of HTlc with general formulas [(Zn,Mg)(1-x)Al(x)(OH)(2)](Cl,OH)(x) and [Mg(1-x)(Fe,Al)(x)(OH)(2)](Cl,OH)(x) were evaluated. The following main conclusions were obtained. For amphoteric solids with structural charge, a point of zero net charge (PZNC) independent of electrolyte concentration (c) exists. A common intersection point (CIP) should appear among the acid-base titration curves at different c, and the pH at the CIP is pH(PZNC). The pK, pK(a1)(int), and pK(a2)(int) may be expressed as a function of pH(PZNC) and sigma(st), and these intrinsic equilibrium constants can be directly calculated from pH(PZNC) and sigma(st). The inert electrolyte chemical binding does not exist for amphoteric surfaces with structural charge. PZNC is not equal to the point of zero net proton charge (PZNPC) when sigma(st) not equal 0. pH(PZNC) > pH(PZNPC) when sigma(st)>0; pH(PZNC) < pH(PZNPC) when sigma(st)<0; and pH(PZNC) = pH(PZNPC) only when sigma(st)=0. With increasing c, the difference between pH(PZNC) and pH(PZNPC) decreases; i.e., pH(PZNPC) moves forward to pH(PZNC) with increasing c. For the HTlc samples studied, with increasing x, the pH(PZNC) and the pK(a1)(int) and pK(a2)(int) decrease, and the pK increases. These results can be explained on the basis of the affinity of metal cations for H(+) or OH(-) and the electrostatic interaction between the charging surface and H(+) or OH(-).