Arginine Complexes Research Articles

Effect of some solvents, IR characterization and TGA investigation of complexes prepared by reactions between Arginine with some metal ions of Hg(II),Cd(II) and Mn(II)

Arginine complexes were prepared with some metal ions of Hg(II),Cd(II) and Mn(II) in a stoichiometric ratio of 1: 2 (Mn+: L), where Mn+ = Mn2+, Cd2+ and Hg+2 ions. The Complexes were characterized by the physicochemical and spectroscopic techniques as electric conductivity, metal contents, IR, UV–Visible, and molar conductance techniques. Thermal studies were carried out by thermo gravimetric analysis. The stoichiometric ratios of the synthesized complexes were confirmed by using molar ratio method. Solvent effect on the electronic spectra of the arginine ligand was examined using solvents with different polarities.

Electrical conductivity measurements of association phenomena for arginine complexes with some transition metals in mono and disaccharide _ water mixture at 310.16K

In the present study we have measured the electrical conductivity of Mn(II), Ni(II), Fe(II) complexes with Arginine in aqueous solutions of mono and di saccharide at (310.16 K), The data were analyzed using Lee-Wheaton(LW) conductivity equation for asymmetrical electrolytes. The conductivity parameter: ionic conductivity (λ) association constant (KA) and the average distance parameter between the ions (R) at the best fit values of the standard deviation () have been calculated, The results are discussed depends on the basis of solvent effect on the conductivity parameter of these complexes. Walden products have also been calculated for each solvent composition.

Isothiocyanate controlled architecture, spectroscopic, and magnetic behavior of copper(II) l–arginine complexes

We synthesized an l–arginine complex with the formula [Cu(l–Arg)2(NCS)]·(NCS)·H2O (1) (l–Arg = l–arginine). Two cis-chelated l–arginine zwitterions form the basal plane, while the weakly N-bonded isothiocyanate is located at the apex of the distorted square pyramidal structure (τ = 0.143). The non-coordinated NCS− anions held layers together in a 3-D supramolecular network. The crystal structure, spectroscopic (FT–IR, Raman, NIR–Vis–UV, EPR) and magnetic properties of 1 have been compared with [Cu(l–Arg)(NCS)2] (2). For 1, two absorptions are observed for ν(C = N) stretching vibrations, corresponding to NCS− ions N-bonded to the central Cu(II) (2077 cm−1) and in the lattice (2057 cm−1). In 2 a single band is observed at 2102 cm−1, indicating equivalent NCS− ions in the structure. The EPR spectra of complexes show anisotropic signal with g⊥ and g|| 2.062, 2.235 (1), and 2.08, 2.225 (2) characteristic for cis-N2O2 and N3O donor sets in the xy plane, respectively. The unpaired electron mainly occupies the dx2–y2 orbital, also confirmed by the single envelope of d–d bands at ca. 16,000 cm−1 for 1 and 16,500 cm−1 for 2. The magnetic properties ofcompounds are characteristic of a very weak antiferromagnetic interaction with J = −0.055 cm−1 and J = −0.096 cm−1 for 1 and 2, respectively.

Arginine Complexes with Simvastatin: Apparent Solubility, In Vitro Dissolution and Solid State Characterization.

Categorized as a Biopharmaceutics Classification System (BCS) Class II drugs, statin exhibit low aqueous solubility and bioavailability thus presenting an obstacle and great challenge to formulation researchers. This paper describes a de novo approach to enhance the aqueous solubility of one of the most commonly prescribed statins i.e., simvastatin (SMV) by forming a complex (SMV-ARG) with cosolute arginine (ARG). The complex has been characterized for its apparent solubility and in vitro dissolution. The solid state characterization has been carried out using Fourier Transform Infra-Red (FTIR) Spectroscopy, Elemental Analysis, X-Ray Powder Diffraction (XRD), Differential Scanning Calorimetry (DSC) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscopy (SEM). Simvastatin-Arginine (SMV-ARG) complex exhibited massive solubility enhancement by 12,000 fold and significant improvement in both acidic and alkaline dissolution media. A conversion of coherent crystalline to non-coherent pattern, and certain extent of amorphization in SMV-ARG complex, fully justifies the enhanced solubility, and hence the dissolution profile. The present study provides a significant evidence that ARG molecules are capable to form a complex with small molecules and increase their aqueous solubility which prove to be beneficial in drug formulation and development.

Experimental and theoretical investigations of infrared multiple photon dissociation spectra of arginine complexes with Zn2+ and Cd2.

Arginine (Arg) complexes with Zn2+ and Cd2+ were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy using light from a free electron laser. Electrospray ionization generated complexes of deprotonated Arg with Zn2+, [Zn(Arg-H)]+, and Arg with CdCl+, CdCl+(Arg). Possible low-energy conformers of these species were found using quantum chemical calculations, and their calculated IR spectra were compared to experimentally measured IRMPD spectra. Calculations were performed at the B3LYP/6-311+G(d,p) level for Zn2+ complexes and B3LYP/def2-TZVP with an SDD effective core potential on cadmium for CdCl+ complexes. [Zn(Arg-H)]+ was found to adopt a charge-solvated, tridentate [N,CO-,Nω'] structure where Zn2+ binds to the backbone amine, carbonyl oxygen, and side-chain terminal guanidine nitrogen (Nω'). The CdCl+(Arg) species was suggested to be a mixture of a dominant (∼85%) charge-solvated, tridentate [N,CO,Nω'] structure where the CdCl+ binds to the backbone amine, carbonyl, and side-chain imine (Nω') and a minor (∼15%) bidentate [N,CO-](Nω'H2+) zwitterionic structure where the metal center binds to the backbone amine and carbonyl oxygen with intramolecular proton migration from the hydroxyl to the Nω' guanidine nitrogen (as designated in parenthesis).

Preparation and Impedance Analysis of Biodegradable Polymer Polyvinyl Alcohol with Amino Acid, Arginine

ABSTRACTBiodegradable polymers have an innumerable use in the field of biomedicine, especially in drug delivery system. Polyvinyl alcohol is one of the biodegradable polymer used as a carrier for drug delivery. Amino acids are necessary for maintaining good health for human beings. The present study focuses on the interaction between polyvinyl alcohol and amino acids. An effort is being taken to prepare polymer membrane based on polyvinyl alcohol complexed with different concentration of arginine, a type of amino acids using water as solvent by solution-casting technique. The amphorousity and complex formation between polyvinyl alcohol and Arignine have been confirmed by X-ray diffraction and FTIR spectroscopy, respecticvely. The thermal behavior of PVA–arginine complexes has been analyzed by differential scanning calorimetry. From AC impedance spectroscopy, ion transport mechanism has been investigated in detail. By using Almond and West formulisms, the parameter such as ion hopping frequency ωp, has been calculated. The polymer membrane 75 Mwt% PVA:25 Mwt% arginine has the highest ionic conductivity as 1.97 × 10−6 S cm−1 at ambient temperature.

Performance of M06, M06-2X, and M06-HF Density Functionals for Conformationally Flexible Anionic Clusters: M06 Functionals Perform Better than B3LYP for a Model System with Dispersion and Ionic Hydrogen-Bonding Interactions

We present a comparative assessment of the performance of the M06 suite of density functionals (M06, M06-2X, and M06-HF) against an MP2 benchmark for calculating the relative energies and geometric structures of the Cl(-)·arginine and Br(-)·arginine halide ion-amino acid clusters. Additional results are presented for the popular B3LYP density functional. The Cl(-)·arginine and Br(-)·arginine complexes are important prototypes for the phenomenon of anion-induced zwitterion formation. Results are presented for the canonical (noncharge separated) and zwitterionic (charge separated) tautomers of the clusters, as well as the numerous conformational isomers of the clusters. We find that all of the M06 functions perform well in terms of predicting the general trends in the conformer relative energies and identifying the global minimum conformer. This is in contrast to the B3LYP functional, which performed significantly less well for the canonical tautomers of the clusters where dispersion interactions contribute more significantly to the conformer energetics. We find that the M06 functional gave the lowest mean unsigned error for the relative energies of the canonical conformers (2.10 and 2.36 kJ/mol for Br(-)·arginine and Cl(-)·arginine), while M06-2X gave the lowest mean unsigned error for the zwitterionic conformers (0.85 and 1.23 kJ/mol for Br(-)·arginine and Cl(-)·arginine), thus providing insight into the types of physical systems where each of these functionals should perform best.

Complexation of anions to gas-phase amino acids: Conformation is critical in determining if the global minimum is canonical or zwitterionic

We report the first MP2 computational study of the Cl−·Arginine and Br−·Arginine complexes, with the clusters being systematically classified into conformational families prior to optimization. The canonical tautomers in particular adopt numerous conformeric structures with close relative energies. Conformer energy differences are of similar magnitude to the canonical–zwitterionic tautomer differences, indicating that it is essential to obtain reliable conformer energies to determine whether the global minimum structure is zwitterionic or canonical for these prototype anionic systems. The zwitterionic and canonical minima are found to be very close in energy for Br−·Arginine, whereas the canonical form is significantly lower for Cl−·Arginine.

Collision-Induced Dissociation of Halide Ion–Arginine Complexes: Evidence for Anion-Induced Zwitterion Formation in Gas-Phase Arginine

We report the first low-energy collisional-induced dissociation studies of the X(-)·arginine (X(-) = F(-), Cl(-), Br(-), I(-), NO(3)(-), ClO(3)(-)) series of clusters to investigate the novel phenomenom of anion-induced zwitterion formation in a gas-phase amino acid. Fragmentation of the small halide ion clusters (F(-)·arginine and Cl(-)·arginine) is dominated by deprotonation of the arginine, whereas the major fragmentation channel for the largest ion clusters (I(-)·arginine and ClO(3)(-)·arginine) corresponds to simple cluster fission into the ion and neutral molecule. However, the fragmentation profiles of Br(-)·arginine and NO(3)(-)·arginine, display distinctive features that are consistent with the presence of the zwitterionic form of the amino acid in these clusters. The various dissociation pathways have been studied as a function of % collision energy and are discussed in comparison to the fragmentation profiles of protonated and deprotonated arginine. Electronic structure calculations are presented for Br(-)·arginine to support the presence of the zwitterionic amino acid in this complex. The results obtained in this work provide important information on the low-energy potential energy surfaces of these anion-amino acid clusters and reveal the presence of several overlapping surfaces in the low-energy region for the Br(-)·arginine and NO(3)(-)·arginine systems.

Exogenous and Cell Surface Glycosaminoglycans Alter DNA Delivery Efficiency of Arginine and Lysine Homopeptides in Distinctly Different Ways

Glycosaminoglycans (GAGs) expressed ubiquitously on the cell surface are known to interact with a variety of ligands to mediate different cellular processes. However, their role in the internalization of cationic gene delivery vectors such as liposomes, polymers, and peptides is still ambiguous and seems to be controlled by multiple factors. In this report, taking peptides as model systems, we show that peptide chemistry is one of the key factors that determine the dependence on cell surface glycosaminoglycans for cellular internalization and gene delivery. Arginine peptides and their complexes with plasmid DNA show efficient uptake and functional gene transfer independent of the cell surface GAGs. On the other hand, lysine peptides and complexes primarily enter through a GAG-dependent pathway. The peptide-DNA complexes also show differential interaction with soluble GAGs. In the presence of exogenous GAGs under certain conditions, arginine peptide-DNA complexes show increased transfection efficiency that is not observed with lysine. This is attributed to a change in the complex nature that ensures better protection of the compacted DNA in the case of arginine complexes, whereas the lysine complexes get destabilized under these conditions. The presence of a GAG coating also ensures better cell association of arginine complexes, resulting in increased uptake. Our results indicate that the role of both the cell surface and exogenous glycosaminoglycans in gene delivery is controlled by the nature of the peptide and its complex with DNA.

Infrared Spectroscopy of Arginine Cation Complexes: Direct Observation of Gas-Phase Zwitterions

The structures of cationized arginine complexes [Arg + M]+, (M = H, Li, Na, K, Rb, Cs, and Ag) and protonated arginine methyl ester [ArgOMe + H]+ have been investigated in the gas phase using calculations and infrared multiple-photon dissociation spectroscopy between 800 and 1900 cm-1 in a Fourier transform ion cyclotron resonance mass spectrometer. The structure of arginine in these complexes depends on the identity of the cation, adopting either a zwitterionic form (in salt-bridge complexes) or a non-zwitterionic form (in charge-solvated complexes). A diagnostic band above 1700 cm-1, assigned to the carbonyl stretch, is observed for [ArgOMe + H]+ and [Arg + M]+, (M = H, Li, and Ag), clearly indicating that Arg in these complexes is non-zwitterionic. In contrast, for the larger alkali-metal cations (K+, Rb+, and Cs+) the measured IR-action spectra indicate that arginine is a zwitterion in these complexes. The measured spectrum for [Arg + Na]+ indicates that it exists predominantly as a salt bridge with zwitterionic Arg; however, a small contribution from a second conformer (most likely a charge-solvated conformer) is also observed. While the silver cation lies between Li+ and Na+ in metal-ligand bond distance, it binds as strongly or even more strongly to oxygen-containing and nitrogen-containing ligands than the smaller Li+. The measured IR-action spectrum of [Arg + Ag]+ clearly indicates only the existence of non-zwitterionic Arg, demonstrating the importance of binding energy in conformational selection. The conformational landscapes of the Arg-cation species have been extensively investigated using a combination of conformational searching and electronic structure theory calculations [MP2/6-311++G(2d,2p)//B3LYP/6-31+G(d,p)]. Computed conformations indicate that Ag+ is di-coordinated to Arg, with the Ag+ chelated by both the N-terminal nitrogen and Neta of the side chain but lacks the strong M+-carbonyl oxygen interaction that is present in the tri-coordinate Li+ and Na+ charge-solvation complexes. Experiment and theory show good agreement; for each ion species investigated, the global-minimum conformer provides a very good match to the measured IR-action spectrum.

Voltage gating and anions, especially phosphate: A model system

The voltage sensor of voltage gated sodium and potassium channels consists of four sets of transmembrane segments, of which one, called S4, contains at least four arginines; these are presumed to each carry positive charges. The channel opening is usually attributed to the outward (i.e., toward the extracellular side of the membrane) motion of S4. The evidence for this motion is based on certain experiments that appear to show differential access to parts of S4 from the intracellular and extracellular sides of the membrane in the open and closed states. A newly available structure [S.B. Long, E.B. Campbell and R. MacKinnon, Crystal structure of a mammalian voltage-dependent Shaker family K + channel. Science 309 (2005) 897–903; S.B. Long, E.B. Campbell, R. MacKinnon, Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 309 (2005) 903–908][1,2] has now been used to argue for a large scale motion, although, as a static structure, it is not conclusive. In this paper, we consider the effect of anions in the surrounding medium. Phosphate is present in the intracellular as well as the extracellular fluid, apparently at hundreds of micromolar concentration, or more. There is evidence in the literature suggesting that phosphate–arginine complexes are rather strong. In a recent calculation one of us [M.E. Green, A possible role for phosphate in complexing the arginines of S4 in voltage gated channels J. Theor. Biol. 233 (2005) 337–341][3] has shown that a model peptide with a 2:1 arg:phosphate complex should have a favorable geometry. Here, we present NMR evidence of the existence of phosphate complexes of a model peptide with two arginines separated by two hydrophobic residues, the same spacing as in S4 segments. The complexes (there are different complexes for HPO 4 2− and for H 2PO 4 − [3]) form with concentrations of peptide in the range of hundreds of micromolar, making it significant in the biological context. NMR spectra provide changes in chemical shift as functions of both phosphate concentration and pH. The resulting curves show titration of the phosphate, with its standard pK. Possible implications for other anion–S4 interactions, including ion pairs rather than complexes, as with Cl −, are also discussed.

X-ray studies on crystalline complexes involving amino acids and peptides. XLII. Adipic acid complexes of L- and DL-arginine and supramolecular association in arginine–dicarboxylic acid complexes

The adipic acid complexes of DL-arginine and L-arginine are made up of zwitterionic, singularly positively charged arginium ions and doubly negatively charged adipate ions, with a 2:1 stoichiometry. One of the two crystallographically independent arginium ions in the L-arginine complex has a conformation hitherto unobserved in crystal structures containing the amino acid. In the present study the structural data on arginine complexes of saturated dicarboxylic acids with 0-5 C atoms separating the two carboxyl functions are given. In terms of molecular aggregation, formic and acetic acid complexes behave in a similar way to those involving fairly long carboxylic acids such as adipic acid. By and large, the supramolecular assembly in complexes involving dicarboxylic acids with 3 or more C atoms separating the carboxyl groups (glutaric, adipic and pimelic acids), and those involving formic and acetic acids, have common features. The aggregation patterns in complexes involving oxalic, malonic and maleic acids do not share striking features among themselves (except for the mode of hydrogen-bonded dimerization of arginium ions) or with those involving larger dicarboxylic acids. Complexes of succinic acid, the shortest linear dicarboxylic acid, share features with those involving shorter as well as longer dicarboxylic acids. The difference in the behaviour of long and short dicarboxylic acids and the ambiguous behaviour of succinic acid can be broadly related to their lengths.

A possible role for phosphate in complexing the arginines of S4 in voltage gated channels

Phosphate ions are known to complex guanidinium groups, which are the side chains of arginine. Voltage gated channels that allow passage of ions through cell membranes, producing, for example the nerve impulse, are in many cases composed of four domains, each with six transmembrane segments. The S4 transmembrane segments of these channels have arginines placed in such a way that they would be expected to complex phosphate. Known phosphate–arginine complexes are reasonably strong. Here, an ab initio calculation reinforces the expectation that a strong complex could form. As a consequence, if the S4 moved, it would carry either no charge, or at most half of what is expected from fully charged arginines. This suggests that it may be necessary to rethink voltage gating models in which the gating current is produced by physical motion of the S4 transmembrane segments.

Programmed Self‐Assembly of Copper(II)‐L‐ and ‐D‐Arginine Complexes with Aromatic Dicarboxylates to Form Chiral Double‐Helical Structures

Programmed Self‐Assembly of Copper(<scp>II</scp>)‐<scp>L</scp>‐ and ‐<scp>D</scp>‐Arginine Complexes with Aromatic Dicarboxylates to Form Chiral Double‐Helical Structures

Electron paramagnetic resonance spectroscopy of the heme domain of inducible nitric oxide synthase: binding of ligands at the arginine site induces changes in the heme ligation geometry.

The electron paramagnetic resonance spectra of the heme domain of inducible nitric oxide synthase (iNOS) demonstrate a close relationship to the corresponding spectra of the neuronal isoform (nNOS). The binding of ligands to the iNOS arginine site perturbs the environment of the high-spin ferriheme in a highly ligand-specific manner. The iNOS forms five-coordinate, high-spin complexes with arginine analogs which are clearly related to the corresponding complexes of nNOS. Studies indicate that the binding of L-arginine, N(omega)-hydroxy-L-arginine (NHA), and N(omega)-methyl-L-arginine (NMA) produces various spectroscopic species closely corresponding to the equivalent complexes of nNOS, while N(omega)-nitro-L-arginine (NNA) binding produces a state which appears intermediate in character between the nNOS NNA and arginine complexes. These spectroscopic studies have permitted the determination of ligand-specific high-spin states which reveal similarities and differences between iNOS and nNOS.

X-ray studies on crystalline complexes involving amino acids and peptides. XXVII. Effect of chirality, specific interactions and characteristic aggregation patterns in the structures of arginine and its complexes with formic acid.

The crystal structures of DL-arginine dihydrate, DL-arginine formate dihydrate and L-arginine formate have been determined and refined using X-ray crystallographic techniques. The three structures, along with other related ones, demonstrate the conformational variability of arginine. The amino acid molecules aggregate essentially in a similar manner in DL-arginine dihydrate and in the known structure of L-arginine dihydrate; the effects arising out of the reversal of the chirality of half the amino acid molecules are absorbed by small local adjustments. However, such a reversal leads to profound differences in aggregation in DL-arginine and L-arginine formates, in contrast to the situation in the corresponding acetates. Thus the effect of chirality on biomolecular aggregation cannot be easily predicted or even rationalized. Arginine-carboxylate interactions in the complexes primarily involve the guanidyl groups and contain specific interactions. Indeed the primary mode of arginine-carboxylic acid aggregation is substantially invariant in the arginine complexes of succinic, acetic and formic acids.

ChemInform Abstract: Interaction Between Copper(II)‐Arginine Complexes and HO2/O‐ 2 Radicals, a Pulse Radiolysis Study.

AbstractSuperoxide radicals are shown to react with all four Cu(II)‐arginine complexes (1:1 and 1:2 complex with the neutral acid, 1:1 complex with the monoanion and 1:2 with one anionic and one neutral ligand) existing between pH 1.5 and 12.5.

Interaction between copper(II)-arginine complexes and HO2/O2- radicals, a pulse radiolysis study

Superoxide radicals were shown to react with all four Cu(II)-arginine complexes that exist between pH 1.5 and 12.5; k/sub 10/(O/sub 2//sup -/ + CuArgH/sup 2 +/) = 3.3 x 10/sup 9/ M/sup -1/ s/sup -1/, k/sub 12/(O/sub 2//sup -/ + Cu(ArgH)/sub 2//sup 2 +/) = 1.3 x 10/sup 7/ M/sup -1/ s/sup -1/, k/sub 13/(O/sub 2//sup -/ + CuArg/sub 2/H/sup +/) = 1 x 10/sup 6/ M/sup -1/ s/sup -1/, k/sub 14/(O/sub 2//sup -/ + CuArg/sup +/) = 1 x 10/sup 8/ M/sup -1/ s/sup -1/. The system was studied in detail at pH 2.0 and pH greater than or equal to7. At low pH the mechanism was shown to proceed via a CuO/sub 2/H/sup 2 +/ complex while at higher pH a superoxide complex of the Cu(II)-arginine complexes was formed. The results are discussed in terms of the currently accepted mechanism by which SOD-Cu/sup 2 +/ dismutates O/sub 2//sup -/ radicals.

The relaxation spectra of nickel(II) and cobalt(II) arginine complexes

AbstractThe temperature‐jump method has been used to determine the nickel(II)‐ and cobalt(II)‐arginine complexation kinetics. In the pH range studied, the neutral form of the ligand, HL, is the attacking, as well as the complexed, ligand species. The reactions reported on are of the type equation image where n = 1, 2, 3 and M is Ni or Co. At 25° and ionic strength 0.1M the association rate constants are: for nickel(II) k1 = 2.3 × 103(±20%), k2 = 2.4 × 104(±20%), k3 = 3.5 × 104(±40%) M−1 sec−1; for cobalt(II) k1 = 1.5 × 105(±20%), k2 = 8.7 × 105(±20%), k3 = 2.0 × 105(±40%) M−1 sec−1. Arginine binds to metal ions less well than homologous chelating agents due to the electrostatic repulsion arising from the positively charged terminus of the zwitterion. Kinetically, the effect appears in the association rate constants with nickel reactions more strongly influenced than cobalt.