Solution-state Studies Research Articles

A Solution and Solid State Study on 2-Hydroxypropyl-β-Cyclodextrin Complexation with Hyodeoxycholic Acid

Hyodeoxycholic acid (HDCA) isa 6-α dihydroxylated natural bile acid capable ofpreventing gallstone formation by reducing the bilecholesterol saturation. However, any attempt to enrichthe bile acid pool with HDCA have failed owing to thepoor solubility of the molecule. To resolve thebioavailability problems, the complexation of HDCAinto the HPβCD cavity was studied in solution(solubility methods, 13C- and 1H-NMRspectroscopy and circular dichroism) and in the solidstate (IR spectroscopy, X-ray diffractometry andthermal analysis). According to the results, the HDCAinclusion took place with 1 : 1 stoichiometry. Theinfluence of different preparation methods of thesolid complex was evaluated for its potential use inappropriate pharmaceutical formulations to improve thebioavailability of HDCA.

Structural studies of two protonated forms of a C2 symmetrical optically active cyclam derivative

Detailed structural analyses, including solid-state (X-Ray), solution-state (NMR) and theoretical (AM1) studies of the two most stable protonated forms — di 3H22+ and tetraprotonated 3H44+ — of a C2 symmetrical, optically active cyclam derivative 3 have been carried out. Important conformational changes in the 14-membered and cyclohexane rings accompany the protonation. A rigid conformation with C2 symmetry stabilized by bifurcated intramolecular hydrogen bonds is obtained for 3H22+, whereas for 3H44+ a dynamic system in solution and a loss of the C2 symmetry in the solid state are found. The effects of temperature and the counter-ion are also discussed.

Palladium(II) Complexation by p-Cyclophane Receptors. A Solution and Solid State Study.

The coordination properties of the macrocyclic ligands 1,4,7,16,19,22-hexamethyl-1,4,7,16,19,22-hexaaza[9.9]-p-cyclophane (L1) and 1,4,7-trimethyl-19,22,28,31-tetraoxa-1,4,7,14,23-pentaaza[9.25]-p-cyclophane (L2) have been studied by means of potentiometric and (1)H and (13)C measurements in aqueous solution. L1 is composed of two equal triamine binding units connected by p-phenylene spacers. L2 presents a similar molecular architecture, a triamine moiety of L1 being replaced by a cyclic N(2)O(4) binding unit. L1 can form both mono- and dinuclear complexes in aqueous solution, while L2 gives only mononuclear species. The potentiometric data indicate that in the L1 dinuclear complex each metal is coordinated by a triamine moiety. In the L2 mononuclear complex the Pd(II) ion is coordinated by the N(3) unit. The N(2)O(4) moiety does not show any binding ability toward Pd(II), but exhibits a high tendency to protonate. These solution data are confirmed by the crystal structures of [Pd(2)Cl(2)L1](ClO(4))(2).H(2)O (a) and [PdClL2H(2)(H(2)O)](ClO(4))(3) (b). In complex a, each Pd(II) ion is four coordinated by the three amine groups of the triaza moiety and a chloride anion, in a square planar geometry. In the mononuclear complex b, the metal is coordinated by the N(3) moiety, with a coordination environment almost equal to that found in complex a. The N(2)O(4) moiety is diprotonated and encapsulates in its cavity a water molecule, held by a hydrogen-bond network. The solution structures of the L1 and L2 complexes have been studied by means of (1)H and (13)C NMR measurements. The analysis of the NMR data reveals that the dinuclear L1 complex and the L2 mononuclear one show structural features in solution almost equal to those found in the solid state. Solution and solid state data indicate that the Pd(II) complexation gives a marked stiffening of the macrocyclic structures.

Complexation of aluminium(III) with 3-hydroxy-2(1H )-pyridinone. Solution state study and crystal structure of tris(3-hydroxy-2(1H )-pyridinonato)aluminium(III)

The formation of complexes between aluminium(III) and 3-hydroxy-2(1H)-pyridinone (HL) in aqueous 0.6 m (Na)Cl at 25 °C has been investigated by means of potentiometric titrations. The following complex stability constants have been evaluated (pKa = 8.590 ± 0.008): log βAlL = 8.59 ± 0.01, log βAlL2 = 16.34 ± 0.03, log βAlL3 = 23.11 ± 0.05, log βAlL3H–1 = 13.85 ± 0.04. The qualitative and quantitative results obtained have been confirmed in part by UV spectrophotometry and 1H NMR spectroscopy. Some potentiometric titrations were executed at 37 °C as well, and the following stability constants were obtained (pKa = 8.452 ± 0.004): log βAlL = 8.19 ± 0.02, log βAlL2 = 16.03 ± 0.04, log βAlL3 = 21.77 ± 0.08, and log βAlL3H–1 = 13.0 ± 0.2. Crystals of the complex AlL3 were obtained and analysed by X-ray diffraction. The neutral species is an octahedral six-co-ordinate complex with the ligand chelating in a bidentate fashion through the pyridinone oxygen and the deprotonated hydroxylic group.

Aqueous co-ordination chemistry using electrospray mass spectrometry of anions: metal(VI)–monosaccharide complexes (M = W or Mo)

Electrospray mass spectrometry has been applied for the first time to the co-ordination chemistry of aqueous anions, using as a model system the reaction of tungstate or molybdate with galactaric (mucic) acid and galacturonic acid; 1∶1, 2∶1 and 1∶2 complexes are found, thus confirming and extending previous solution-state studies. The gas-phase ions may undergo minor dehydration, and some decarboxylation. Nevertheless, the method is shown to provide a rapid and simple means for identifying mixtures of anionic complexes in dilute aqueous solution, even when their binding constants are modest.

4-Amino-6-methoxy-2-methylthiopyrimidine and Hg (II) system: solution and solid state studies on metalated and N-coordinated species Crystal structure of [Hg 2 (HL) 2(μ-Cl) 2Cl 2

The acid-base behaviour of the pyrimidine analogue 4amino-6-methoxy-2-methylthiopyrimidine (HL) and the reactivity with HG(II) ion have been studied by potentiometric methods at 25 °C and 0.1 M KCl ionic strength. By fixing the appropriate pH conditions, solid species with stoichiometries HgLCl·H 2O and Hg 2(HL) 2Cl 4 have been isolated. The spectroscopic study of the solids shows that HgLCI·H 2O is a C(5)-organomercurial species, whereas the structure of Hg 2(HL) 2Cl 4 has been determined by single crystal X-ray diffraction methods. Hg 2(HCL) 2Cl 4 is a binuclear complex with two Hg(II) ions tetrahedrally coordinated by a terminal chloride ion, a HL molecule and two bridging chloride ions. The Hg(II) ion is coordinated to HL via the N(3) endocyclic atom.

Coordination of 2-hydroxyhippuric acid to the copper(II) ion: a solution and solid state study

Abstract The solution and solid state behaviour of the binary system Cu(II)-2-hydroxyhippuric acid (2-OHhipH) and the corresponding ternary system with 2,2′-bipyridine (bpy) were investigated through pH-metric titrations and X-ray crystallography. In solution the species [CuLH −1 ] − and [CubpylL] were found to prevail in the binary and in the ternary system, respectively, both involving metal coordination of the phenolate oxygen. A spectrophotometric p K a of 5.2(2) was determined for the deprotonation of the phenolic hydroxy group in the ternary system. The crystals of the complex [Cu(bpy)(2-OHhip)] 2 ·8H 2 O were found suitable for X-ray structure determination. The crystals of the compound C 19 H 23 CuN 3 O 8 are monoclinic, space group P2 1 /c,a = 7.717(2), b = 11.502(2), c = 23.275(4) A , β = 94.86(3)°, Z = 4, R = 0.033, R w = 0.035 . The structure consists of dimeric [Cu(bpy) (2-OHhip)] 2 units and lattice water molecules. The Cu(II) atom is pentacoordinated by the two nitrogen atoms of the bpy molecule and carbonyl and phenolate ocygen atoms of the ligand in the equatorial plane, and by a bridged phenolate oxygen in the apical position, giving rise to a distorted square pyramidal geometry. The binding mode of 2-OHhipH is discussed by reference to related ligands.

CO(2) Fixation by Novel Copper(II) and Zinc(II) Macrocyclic Complexes. A Solution and Solid State Study.

Solutions containing Zn(II) and Cu(II) complexes with [15]aneN(3)O(2) rapidly adsorb atmospheric CO(2) to give {[ZnL](3)(&mgr;(3)-CO(3))}.(ClO(4))(4) (2) and {[CuL](3)(&mgr;(3)-CO(3))}.(ClO(4))(4) (4) complexes. The crystal structures of both complexes have been solved (for 2, space group R3c, a, b = 22.300(5) Å, c = 17.980(8) Å, V = 7743(4) Å(3), Z = 6, R = 0.0666, R(w)(2) = 0.1719; for 4, space group R3c, a, b = 22.292(7) Å, c = 10.096(8) Å, V = 7788(5) Å(3), Z = 6, R = 0.0598, R(w)(2) = 0.1611), and the spectromagnetic behavior of 4 has been studied. In both compounds a carbonate anion triply bridges three metal cations. Each metal is coordinated by one oxygen of the carbonate, three nitrogens, and an oxygen of the macrocycle; the latter donor weakly interacts with the metals. Although the two compounds are isomorphous, they are not isostructural, because the coordination geometries of Zn(II) in 2 and Cu(II) in 4 are different. The mixed complex {[CuZn(2)L(3)](&mgr;(3)-CO(3))}.(ClO(4))(4) has been synthesized. X-ray analysis (space group R3c, a, b = 22.323(7) Å, c = 17.989(9) Å, V = 7763(5) Å(3), Z = 6, R = 0.0477, R(w)(2) = 0.1371) and EPR measurements are in accord with a &mgr;(3)-carbonate bridging one Cu(II) and two Zn(II) ions in {[CuZn(2)L(3)](&mgr;(3)-CO(3))}(4+). Both the Zn(II) and Cu(II) cations exhibit the same coordination sphere, almost equal to that found in the trinuclear Zn(II) complex 2. The systems Zn(II)/L and Cu(II)/Lhave been studied by means of potentiometric measurements in 0.15 mol dm(-)(1) NaCl and in 0.1 mol dm(-)(3) NaClO(4) aqueous solutions; the species present in solution and their stability constants have been determined. In both systems [ML](2+) species and hydroxo complexes [M(II)LOH](+) (M = Zn, Cu) are present in solution. In the case of Cu(II), a [CuL(OH)(2)] complex is also found. The process of CO(2) fixation is due to the presence of such hydroxo-species, which can act as nucleophiles toward CO(2). In order to test the nucleophilic ability of the Zn(II) complexes, the kinetics of the promoted hydrolysis of p-nitrophenyl acetate has been studied. The [ZnLOH](+) complex promotes such a reaction, where the Zn(II)-bound OH(-) acts as a nucleophile to the carbonyl carbon. The equilibrium constants for the addition of HCO(3)(-) and CO(3)(2)(-) to the [ZnL](2+) complex have been potentiometrically determined. Only [ML(HCO(3))](+) and [ML(CO(3))] species are found in aqueous solution. A mechanism for the formation of {[ML](3)(&mgr;(3)-CO(3))}.(ClO(4))(4) is suggested.

Design, Synthesis, and Evaluation of Bile Acid-Based Molecular Tweezers

A family of bile acid-based molecular tweezers (7−9) has been constructed readily from simple precursors. Binding experiments with various electron deficient aromatic compounds showed that tweezer 8 binds trinitrofluorenone 10e with an association constant of 220 M-1 in CDCl3. Single-crystal X-ray analysis of compound 8 shows aromatic−aromatic interactions producing a two-dimensional lattice of pyrene units. Tweezer 8 was immobilized on Merrifield resin, and binding studies have shown that these data compare well with those of the solution state studies.

Analysis of the hyperfine-shifted nitrogen-15 resonances of the oxidized form of Anabaena 7120 heterocyst ferredoxin.

Hyperfine-shifted nitrogen signals have been detected in one-dimensional 15N NMR spectra of oxidized Anabaena 7120 heterocyst ferredoxin labeled uniformly with 15N. Several of these have been classified by amino acid type by reference to results from selective 15N-labeling studies. Remarkable agreement is seen between a dipole-dipole analysis of the 15N T1 relaxation and the distances of several of the nitrogens from the irons of the cluster as derived from the X-ray structure of this protein [Jacobson, B. L., Chae, Y. K., Markley, J. L., Rayment, I., & Holden, H. M. (1993) Biochemistry 32, 6788-6793]. The agreement is within experimental error for hyperfine-shifted nitrogens that are at least 4.2 A distant from either of the irons of the cluster; however, the simple model appears to fail for hyperfine-shifted nitrogens that are closer to the cluster. The failure of the model for short distances may stem either from a breakdown of the point-dipole approximation and/or from neglect of delocalization of unpaired electron density from the iron ions to other atoms. Even with the above limitations, dipolar analysis of 15N relaxation should provide useful distance constraints for solution-state studies of iron-sulfur proteins.

Solution and solid state studies of mixed ligand binuclear complexes containing one binucleating ligand

Stability constants of homobinuclear binary Cu(II) complexes of the dinucleating ligands, having equivalent coordination sites, 5,5′-methylene-bis-salicylaldehyde (H2A1), 5,5′-methylene-bis-(3-bromosalicylaldehyde) (H2A2), and 5,5′-methylene-bis-(3-nitrosalicylaldehyde) (H2A3), and mixed ligand Cu(II) complexes with one of the above ligands and bipyridyl (L1) or 1,10-phenanthroline (L2) as second ligand, have been determined potentiometrically in water:dioxane medium (50:50 and 30:70,v/v using a computer programme. The values of [Formula: see text] and [Formula: see text] have been compared within the series of complexes having different H2A and L. Probable explanations for the stability order have been extended. The complexes (Cu2AL2)(ClO4)2 have been isolated and characterized by elemental analysis, electronic and ESR spectral, and magnetic studies.

A molecular model for membrane fusion based on solution studies of an amphiphilic peptide from HIV gp41.

The mechanism of protein-mediated membrane fusion and lysis has been investigated by solution-state studies of the effects of peptides on liposomes. A peptide (SI) corresponding to a highly amphiphilic C-terminal segment from the envelope protein (gp41) of the human immunodeficiency virus (HIV) was synthesized and tested for its ability to cause lipid membranes to fuse together (fusion) or to break open (lysis). These effects were compared to those produced by the lytic and fusogenic peptide from bee venom, melittin. Other properties studied included the changes in visible absorbance and mean particle size, and the secondary structure of peptides as judged by CD spectroscopy. Taken together, the observations suggest that protein-mediated membrane fusion is dependent not only on hydrophobic and electrostatic forces but also on the spatial arrangement of the amino acid residues to form an amphiphilic structure that promotes the mixing of the lipids between membranes. A speculative molecular model is proposed for membrane fusion by alpha-helical peptides, and its relationship to the forces involved in protein-membrane interactions is discussed.

Mixed valence in conjugated anion radicals, solution and solid state studies

Electron localization in anion radicals of aromatic compounds built with two electrophores was studied using Vis, NIR, IR and ESR spectroscooy and electrochemistry. N,N′,-Bis (2,5-di-tert-butylphenyl)-2,3,6,7-anthracene-docarboximide anion radical has the odd electron mainly localized on the anthracene bridge. This contrasts with its diquinone analog, 1,4,8,11-pentacenetetrone, which has the odd electron localized on one quinone at a time. The anion radical of the tatrakis-(N-cyanoimine) derivative of 5,7,12,14-pentacenetetrone ( 3 − ) is delocalized. The solid state conductivity of the salts M +, 3 − ranges from 10 −4 S cm −1 for M=Bu 4 N to 0.4 S cm −1 for M=Na

Some Multinuclear NMR Solution and Solid State Studies on 1,8-Bis(dimethylamino)naphthalene and Its Complex with Tetrazole

Abstract 13C and 15N NMR spectra are measured for 1,8-bis(dimethylamino)naphthalene and its complex with tetrazole in both solution and the solid state. On the basis of the solution and solid state 15N results, an equilibrium involving the half protonated form of the base in the solution of the complex salt was identified. On the other hand, it is found that the 13C results for the solutions are closely similar to those found for the solid state, and are rather insensitive to salt formation.

Solution and solid state studies of some ternary complexes of Cu(II) involving heteroaromatic N-bases and o-hydroxy aromatic carbonyls

Stability constants of some ternary complexes of o-hydroxy aldehydes (HL) with Cu(II) as central metal ion and bis(2-pyridyl)amine (dpa) and 5-nitro-1,10-phenanthroline (5-N-phen) as primary ligands (A) have been determined potentiometrically in 50% aqueous dioxane medium using a computer technique. The values of [Formula: see text] have been compared within the series as well as with the corresponding bipyridyl complexes. The stability order has been explained on the basis of the electron repulsion concept. The complexes have been isolated in the solid state and characterized by elemental analysis, conductance and magnetic measurements, and ir and electronic spectral studies. Shifts in ligand field absorption wave numbers of the mixed ligand complex from the average value of the ligand field absorption wave numbers of [MA2]2+ and [ML2] have been correlated with the potentiometrically determined Δ log K values.

1H/29Si cross-polarization dynamics in amorphous hydrogenated silicon

A modified cross-polarization method is used to simplify the solid-state magic-angle spinning 29Si-NMR spectrum of a-Si:H. At least three magnetically distinct environments are resolved. A microscopic model for the cross-polarization dynamics is used to assign the components of the spectrum. Contrary to expectations from solution state studies of low-molecular-weight silanes, the signals from 29Si bonded directly to hydrogen are shifted to a lower field compared to quaternary Si. This observation is rationalized on the basis of theoretical models and photoemission spectroscopy results published by other groups. A suggestion for the nature of shallow states is offered on the basis of the NMR results.

Structural analysis of the urinary lignan 2,3-bis-(3-hydroxybenzyl)butan-4-olide (‘enterolactone’). A 400 MHz nuclear magnetic resonance study for the solution state and X-ray study for the crystal state

Studies of the 13C and 1H (at 400 MHz) spectra of the title compound, with application of the nuclear Overhauser effect (n.O.e.) and decoupling difference methods, have permitted the first complete spectral assignments for a lignan of the dibenzylbutane type, including distinction between the two benzylic groups, which differ in their relationship to the lactone ring. It is now clear that previous analyses of n.m.r. spectra for some structurally related plant lignans have led to incorrect 1H assignments, whereas 13C assignments have previously been incomplete. An X-ray crystallographic study has established the conformation of enterolactone in the solid state, which corresponds to the preferred conformation in solution, inferred from n.m.r. data.

Solution and Solid State Studies of Tetrafluoro-7,7,8,8-Tetracyano-p-Quinodimethane, TCNQF4. Evidence for Long-Range Amphoteric Intermolecular Interactions and Low-Dimensionality in the Solid State Structure

Abstract Solution and solid state studies of TCNQF4 are reported. The electron affinity of TCNQF4 has been derived from spectral observations of the visible-near IR charge-transfer band for the pyrene complex and compared to that derived from the half-wave potentials used to characterize its reactivity in solution. It is demonstrated that the series, TCNQ, TCNQF to TCNQF4 shows a monotonic increase in reactivity with increasing fluorine substitution. Crystals of TCNQF4, grown from acetonitrile, are orthorhombic; space group Pbca, with the following crystal data: a = 14.678(7)A, b = 9.337(5)A, c = 8.174(2)A, V = 1120.0(6)A3, Z = 4 [based on a molecular weight for C12N4F4 = 276.22], Dmeasd = 1.65(1) g cm−3, Dcalcd = 1.64 g cm−3. Full matrix least-squares refinement (including anisotropic thermal parameters for all atoms) using 1763 counter-collected Fa's led to a final R value of 0.067 and a final weighted R value of 0.036. The observed molecular geometry of TCNQF4 is compared to that of its parent molecule TCNQ and to its monoanion found in some charge-transfer complexes. Crystal packing of TCNQF4 affords two interesting types of intermolecular acid/base (or donor/acceptor) interactions utilizing the cyano nitrogen atoms and the fluorinated carbon atoms of the quininoid ring. This subtle amphoterism exhibited by TCNQF4 leads to reduced dimensionality for the crystalline motif and is compared to similar solid state interactions found in several other molecules with π-bonded ring systems containing highly-electronegative substituents.

Solution and Solid State Studies on the Interactions of Protonated Cytosine Salts. IV. Asymmetric Interbase Hydrogen Bonding and Interpyrimidine Base Stacking in Triply Hydrogen-Bonded Cytosine Complexes. Crystal and Molecular Structure of Bis[1-Methylcytosine, 1-Methylcytosinium] Hexafluorosilicate Dihydrate

Abstract The crystal and molecular structures of the complex bis(1-methylcytosine, 1-methylcytosinium) hexafluorosilicate dihydrate are reported. In the solid, a 1:1 triply hydrogen-bonded complex consisting of one protonated and one neutral 1-methylcytosine base is observed. The hydrogen bonding in the complex cation is asymmetric, and the asymmetry in the interbase hydrogen bonding is stimulated to a large part by base stacking. The observed infinite, helical array of stacked complexes, in which the base stacking is strong [mean stacking distance = 3.36A] is such that the molecular overlap is between protonated and neutral 1-methylcytosine bases. The asymmetric interbase hydrogen bonding and the protonated/neutral base stacking mode coexist in a synergistic interrelationship which maximizes the molecular and crystal forces. The results found in this study are compared with a variety of other systems in which asymmetrically hydrogen-bonded cytosine complexes are observed, and it is found that although base stacking is also a predominant feature of these complexes in the solid, the base stacking found in this study is different.

STEREOCHEMICAL STUDIES ON CYCLIC PEPTIDES

Conformational analysis of cyclic pentapeptides having two intra-ring 3 leads to 1 hydrogen bonds has been carried out. It is found that the structure can easily be formed with trans planar peptide units without causing significant angular strain at the alpha-carbon atoms. Four different types of conformations designated Types I--IV are possible for the backbone structure. Details of these four types of conformations and also the accommodating possibility of these types for allglycyl and all-alanyl residues are presented. Three of the four types have relatively low energies for glycyl residues whereas the other one has a slightly higher energy. When alanyl residues are introduced at the five alpha-carbon atoms, the types that are energetically favourable depend upon the sequence of isomers. Energy calculations have also been carried out for the combinations of glycyl, L- and D-alanyl residues. The theoretical results are compared with available experimental observations both from solution and solid state studies.