Arginine In Aqueous Solution Research Articles

Arginine-Functional Methacrylic Block Copolymer Nanoparticles: Synthesis, Characterization, and Adsorption onto a Model Planar Substrate.

Recently, we reported the synthesis of a hydrophilic aldehyde-functional methacrylic polymer (Angew. Chem., 2021, 60, 12032-12037). Herein we demonstrate that such polymers can be reacted with arginine in aqueous solution to produce arginine-functional methacrylic polymers without recourse to protecting group chemistry. Careful control of the solution pH is essential to ensure regioselective imine bond formation; subsequent reductive amination leads to a hydrolytically stable amide linkage. This new protocol was used to prepare a series of arginine-functionalized diblock copolymer nanoparticles of varying size via polymerization-induced self-assembly in aqueous media. Adsorption of these cationic nanoparticles onto silica was monitored using a quartz crystal microbalance. Strong electrostatic adsorption occurred at pH 7 (Γ = 14.7 mg m-2), whereas much weaker adsorption occurred at pH 3 (Γ = 1.9 mg m-2). These findings were corroborated by electron microscopy, which indicated a surface coverage of 42% at pH 7 but only 5% at pH 3.

Near-IR Fluorescent Recognition of Arginine: High Chemoselectivity and Enantioselectivity Promoted by La3.

The first near IR fluorescent probe for the chemoselective and enantioselective recognition of arginine in aqueous solution is reported in this work. This probe, made of a 1,1'-binaphthyl-based chiral aldehyde unit and a rhodamine-based near IR chromophore, in combination with La3+ exhibits highly chemoselective as well as enantioselective fluorescent enhancement with arginine at λ=764 nm upon excitation at λ=690 nm. Little or no fluorescent response is observed toward the chirality miss-matched arginine enantiomer or other common amino acids and their enantiomers. This probe also allows visual discrimination of the arginine enantiomers because of its fast and distinct color change upon interaction with the substrate.

Effect of Functionalization of the Polycaprolactone Film Surface on the Mechanical and Biological Properties of the Film Itself.

The lack of suitable functional groups for cell adhesion on the surface of Polycaprolactone (PCL) is one of the main limitations in order to use PCL for biomedical applications. The aim of this research is to modify the PCL film surface using arginine, via an aminolysis reaction. In this regard, after PCL films formation by casting method, they were immersed in arginine solutions of various concentration at room temperature or then heated to 40 °C and in the presence of isopropanol or without it. To assess the structure of the modified surface, its wettability, and mechanical properties, methods of measuring the contact angle and the strip tensile test were used, and to compare the degree of attachment and the rate of cell proliferation, the method of fluorescent staining of cultured cells was used. The change in protein synthesis by cells on the modified surface was assessed using Western blotting. The results obtained show that the treatment of PCL films with an aqueous solution of arginine at room temperature for 1 day increases the hydrophilicity of the surface. Wherein surface modification led to a two-fold decrease of mechanical strength and flow stress, but elongation increase by about 30% for PCL films after modification in 0.5 M aqueous arginine solution at room temperature. Moreover, cell attachment and proliferation, as well as collagen synthesis, were significantly enhanced after arginine modification. The proposed simple and effective method for modifying PCL films with arginine significantly expands the possibilities for developing biocompatible scaffolds for tissue engineering.

Influence of Aqueous Arginine Solution on Regulating Conformational Stability and Hydration Properties of the Secondary Structural Segments of a Protein at Elevated Temperatures: A Molecular Dynamics Study.

The effects of aqueous arginine solution on the conformational stability of the secondary structural segments of a globular protein, ubiquitin, and the structure and dynamics of the surrounding water and arginine were examined by performing atomistic molecular dynamics (MD) simulations. Attempts have been made to identify the osmolytic efficacy of arginine solution, and its influence in guiding the hydration properties of the protein at an elevated temperature of 450 K. The similar properties of the protein in pure water at elevated temperatures were computed and compared. Replica exchange MD simulation was performed to explore the arginine solution's sensitivity in stabilizing the protein conformations for a wide range of temperatures (300-450 K). It was observed that although all the helices and strands of the protein undergo unfolding at elevated temperature in pure water, they exhibited native-like conformational dynamics in the presence of arginine at both ambient and elevated temperatures. We find that the higher free energy barrier between the folded native and unfolded states of the protein primarily arises from the structural transformation of α-helix, relative to the strands. Our study revealed that the water structure around the secondary segments depends on the nature of amino acid compositions of the helices and strands. The reorientation of water dipoles around the helices and strands was found hindered due to the presence of arginine in the solution; such hindrance reduces the possibility of exchange of hydrogen bonds that formed between the secondary segments of protein and water (PW), and as a result, PW hydrogen bonds take longer time to relax than in pure water. On the other hand, the origin of slow relaxation of protein-arginine (PA) hydrogen bonds was identified to be due to the presence of different types of protein-bound arginine molecules, where arginine interacts with the secondary structural segments of the protein through multiple/bifurcated hydrogen bonds. These protein-bound arginine formed different kinds of bridged PA hydrogen bonds between amino acid residues of the same secondary segments or among multiple bonds and helped protein to conserve its native folded form firmly.

Analyzing the driving forces of insulin stability in the basic amino acid solutions: A perspective from hydration dynamics.

Amino acids having basic side chains, as additives, are known to increase the stability of native-folded state of proteins, but their relative efficiency and the molecular mechanism are still controversial and obscure as well. In the present work, extensive atomistic molecular dynamics simulations were performed to investigate the hydration properties of aqueous solutions of concentrated arginine, histidine, and lysine and their comparative efficiency on regulating the conformational stability of the insulin monomer. We identified that in the aqueous solutions of the free amino acids, the nonuniform relaxation of amino acid-water hydrogen bonds was due to the entrapment of water molecules within the amino acid clusters formed in solutions. Insulin, when tested with these solutions, was found to show rigid conformations, relative to that in pure water. We observed that while the salt bridges formed by the lysine as an additive contributed more toward the direct interactions with insulin, the cation-π was more prominent for the insulin-arginine interactions. Importantly, it was observed that the preferentially more excluded arginine, compared to histidine and lysine from the insulin surface, enriches the hydration layer of the protein. Our study reveals that the loss of configurational entropy of insulin in arginine solution, as compared to that in pure water, is more as compared to the entropy loss in the other two amino acid solutions, which, moreover, was found to be due to the presence of motionally bound less entropic hydration water of insulin in arginine solution than in histidine or lysine solution.

Uranyl Organic Framework as a Highly Selective and Sensitive Turn-on and Turn-off Luminescent Sensor for Dual Functional Detection Arginine and MnO4.

Five new uranyl coordination polymers were prepared by the hydrothermal method based on 5-nitroisophthalic acid (H2nip) as (UO2)(nip)(2,2'-bpy) (1), (H24,4'-bpy)·[(UO2)3(nip)4]·(4,4'-bpy) (2), (H2bpe)·[(UO2)0.5(nip)] (3), (H2 bpp)·[(UO2)2-(nip)3]·H2O (4), and (H2tmp)·[(UO2)(nip)2](5) [2,2'-bpy = 2,2'-bipyridine, 4,4'-bpy = 4,4'-bipyridine, bpe = 4,4'-vinylenedipyridine, bpp = 4,4' -trimethylenedipyridine, tmp = tetramethylpyrazine]. All of these synthesized complexes have been characterized by single crystal and powder X-ray diffraction, IR spectra, thermogravimetric analysis, elemental analysis, and luminescent properties. In particular, it is found that compounds 1 and 4 can be used as a luminescent sensor to efficiently detect arginine in aqueous solution by means of "turn-on"; the detection limits were 1.06 × 10-6 and 6.42 × 10-6 mol/L, respectively. Moreover, 4 can also be used as a bifunctional sensor for selective sensing of MnO4- anion by "turn-off". The detection limit of MnO4- in water was 1.79 × 10-6 mol/L; the Ksv was 1.88 × 104. The sensing effect of arginine in simulated grape juice samples and MnO4- in simulated river water samples was also investigated by this sensing system with high recovery. In addition, the possible mechanism of sensing arginine and MnO4- in the aqueous solution was discussed.

Thermodynamics and solute-solvent interactions of lovastatin in an aqueous arginine solution

Lovastatin (LVS) is an effective therapeutic and prophylactic agent in several cardiovascular disorders. However, it has low bioavailability. This study investigated solute-solvent and solute-cosolute interactions and assessed thermodynamic parameters that contributed to LVS solubility enhancement in the presence of arginine (ARG) as a hydrotropic agent. The electrolytic conductance of LVS-ARG binary system was measured at temperatures from 298.15 K to 313.15 K. Conductometric parameters such as limiting molar conductance was evaluated. Additionally, thermodynamic parameters (ΔG0, ΔH0, ΔS0 and ES) involved in the association process of the solute in the aqueous solution of ARG solution were determined systematically. Solubility markedly improved 43-fold in the LVS-ARG complex compared to LVS alone. The analysed data from values of molar conductance and activation energy suggested favourable solubilisation, with a stronger solute-solvent interaction between LVS-ARG in water at higher temperatures. ARG and LVS complexation caused by strong molecular interactions was confirmed by spectral results. Hence, the addition of ARG as a co-solute was proven to enhance LVS solubility in water. The obtained data will ultimately enable the development of desired highly soluble, more efficient and safer LVS preparations.

A polyelectrolyte based ratiometric optical sensor for Arginine and Lysine

The crucial involvement of amino acids in various physiological processes and their ability to function as effective biomarkers for a variety of diseased conditions has inspired a significant activity in conceptualizing sensor system for amino acids, although there are still limited reports which aim to detect basic amino acids with simpler design yet with high sensitivity and selectivity. Herein, we report a ratiometric optical sensor that is based on Arginine and Lysine-induced disintegration of a supramolecular assembly, leading to significant modulation in the monomer-aggregate equilibrium, which yields a ratiometric signal that has been used for quantification of Lysine and Arginine in aqueous solutions. Our sensor design overcomes many disadvantages that are associated with the existing optical sensing schemes, such as, technically demanding and time-consuming synthetic protocols for probe synthesis, limited aqueous solubility, and more importantly, most of the previously reported sensors operate via single wavelength based measurements, which makes their performance error prone to a variety of analyte-independent factors which can be overcome by ratiometric detection as achieved here. Overall, we have devised a label free, rapid, simple, dual-sensing, ratiometric sensor for the detection of basic amino acids. Importantly, our sensing system also shows response in the human serum matrix.

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.

Supramolecular Dye Aggregate Assembly Enables Ratiometric Detection and Discrimination of Lysine and Arginine in Aqueous Solution.

Constructing sensor systems for rapid and selective detection of small biomolecules such as amino acids is a major area of focus in bioanalytical chemistry. Considering the biological relevance of arginine and lysine, significant efforts have been directed to develop fluorescent sensors for their detection. However, these developed sensors suffer from certain disadvantages such as poor aqueous solubility, technically demanding and time-consuming synthetic protocols, and more importantly, most of them operate through single wavelength measurements, making their performance prone to small variations in experimental conditions. Herein, we report a ratiometric sensor that operates through lysine- and arginine-induced dissociation of a supramolecular assembly consisting of emissive H-aggregates of a molecular rotor dye, thioflavin-T (ThT), on the surface of a polyanionic supramolecular host, sulfated β-cyclodextrin. This disassembly brings out the modulation of monomer–aggregate equilibrium in the system which acts as an ideal scheme for the ratiometric detection of lysine and arginine in the aqueous solution. Besides facile framework of our sensor system, it employs a commercially available inexpensive probe molecule, ThT, which provides an added advantage over other sensor systems that employ synthetically demanding probe molecules. Importantly, the distinctive feature of the ratiometric detection of arginine and lysine provides an inherent advantage of increased accuracy in quantitative analysis. Interestingly, we have also demonstrated that arginine displays a multiwavelength distinctive recognition pattern which distinguishes it from lysine, using a single supramolecular ensemble. Furthermore, our sensor system also shows response in heterogeneous, biologically complex media of serum samples, thus extending its possible use in real-life applications.

Spray drying of poorly soluble drugs from aqueous arginine solution

Co-amorphous drug-amino acid mixtures have shown potential for improving the solid-state stability and dissolution behavior of amorphous drugs. In previous studies, however these mixtures have been produced mainly with small-scale preparation methods, or with methods that have required the use of organic solvents or other dissolution enhancers. In the present study, co-amorphous ibuprofen-arginine and indomethacin-arginine mixtures were spray dried from water. The mixtures were prepared at two drug-arginine molar ratios (1:1 and 1:2). The properties of the prepared mixtures were investigated with differential scanning calorimetry, X-ray powder diffractometry, Fourier-transform infrared spectroscopy and a 24h, non-sink, dissolution study. All mixtures exhibited a single glass transition temperature (Tg), evidence of the formation of homogenous single-phase systems. Fourier transform infrared spectroscopy revealed strong interactions (mainly salt formation) that account for the positive deviation between measured and estimated Tg values. No crystallization was observed during a 1-year stability study in either 1:1 or 1:2 mixtures, but in the presence of moisture, handling difficulties were encountered. The formation of co-amorphous salts led to improved dissolution characteristics when compared to the corresponding physical mixtures or to pure crystalline drugs.

Guanidinium Group Remains Protonated in a Strongly Basic Arginine Solution.

Knowledge of the acid dissociation constant of an amino acid has very important ramifications in the biochemistry of proteins and lipid bilayers in aqueous environments because charge and proton transfer depend on its value. The acid dissociation constant for the guanidinium group in arginine has historically been posited as 12.5, but there is substantial variation in published values over the years. Recent experiments suggest that the dissociation constant for arginine is much higher than 12.5, which explains why the arginine guanidinium group retains its positive charge under all physiological conditions. In this work, we use X-ray photoelectron spectroscopy to study unsupported, aqueous arginine nanoparticles. By varying the pH of the constituent solution, we provide evidence that the guanidinium group is protonated even in a very basic solution. By analyzing the energy shifts in the C and N X-ray photoelectron spectra, we establish a molecular level picture of how charge and proton transport in aqueous solutions of arginine occur.

Solubility enhancement of simvastatin by arginine: thermodynamics, solute-solvent interactions, and spectral analysis.

We examined the solubility of simvastatin in water in 0.01 mol·dm−3, 0.02 mol·dm−3, 0.04 mol·dm−3, 0.09 mol·dm−3, 0.18 mol·dm−3, 0.36 mol·dm−3, and 0.73 mol·dm−3 arginine (ARG) solutions. The investigated drug is termed the solute, whereas ARG the cosolute. Phase solubility studies illustrated a higher extent of solubility enhancement for simvastatin. The aforementioned system was subjected to conductometric and volumetric measurements at temperatures (T) of 298.15 K, 303.15 K, 308.15 K, and 313.15 K to illustrate the thermodynamics involved and related solute–solvent interactions. The conductance values were used to evaluate the limiting molar conductance and association constants. Thermodynamic parameters (ΔG0, ΔH0, ΔS0, and Es) for the association process of the solute in the aqueous solutions of ARG were calculated. Limiting partial molar volumes and expansibilities were evaluated from the density values. These values are discussed in terms of the solute–solvent and solute–cosolute interactions. Further, these systems were analyzed using ultraviolet–visible analysis, Fourier-transform infrared spectroscopy, and 13C, 1H, and two-dimensional nuclear overhauser effect spectroscopy nuclear magnetic resonance to complement thermophysical explanation.

Ternary system based on fluorophore-surfactant assemblies--Cu²⁺ for highly sensitive and selective detection of arginine in aqueous solution.

A new cationic dansyl derivative-based (DIlSD) fluorescence probe was designed and synthesized. Its combination with anionic surfactant SDS assemblies shows enhanced fluorescence intensity and blue-shifted maximum wavelength. Its fluorescence can be slightly quenched by Cu(2+); however, the fluorescence quenching efficiency by Cu(2+) is highly increased upon titration of arginine (Arg). As a result, the ternary system containing the cationic fluorophore, anionic surfactant, and Cu(2+) functions as a highly sensitive and selective sensor to Arg. The optimized sensor system displays a detection limit of 170 nM, representing the highest sensitivity to Arg in total aqueous solution by a fluorescent sensor. Control experiments reveal that the imidazolium groups in the fluorophore, the anionic surfactant, and Cu(2+) all play important roles in the process of sensing Arg. The electrostatic interaction between the cationic fluorophore and anionic surfactants facilitates the binding of imidazolium rings with Cu(2+), the surfactant surface-anchored Cu(2+) is responsible for further binding of Arg, and the electrostatic interaction between anionic surfactants and positively charged amino acids accounts for the selective responses to Arg.

Effect of acidity on the equilibria of formation of mixed Co2+ complexes with heparin and arginine in aqueous solutions at 37°C

Results from studying interactions in the heparin-Co2+ ion-arginine system are presented. The constants of formation of mixed Co2+ complexes with heparin and arginine in aqueous solutions in a broad pH range at 37°C are determined potentiometrically. The chemical equilibria in the system are simulated and the stoichiometry of formation of the complex forms is determined.

Effect of Hydroxylamine Sulfate on Volumetric Behavior of Glycine, L‐Alanine, and L‐Arginine in Aqueous Solution

The apparent molar volumes of glycine, L‐alanine, and L‐arginine in aqueous hydroxylamine sulfate solutions have been determined at T = 298.15 K and atmospheric pressure. The standard partial molar volumes, , corresponding partial molar volumes of transfer, , and hydration numbers, NH, have been calculated for these α‐amino acids from the experimental data. The values are positive for glycine, L‐alanine, and L‐arginine and are all increased with the increase in the concentration of hydroxylamine ions. These parameters obtained from the volumetric data are interpreted in terms of various mixing effects between amino acids and hydroxylamine sulfate in aqueous solutions.

Protein-Associated Cation Clusters in Aqueous Arginine Solutions and Their Effects on Protein Stability and Size

Arginine is one of the most prominent residues in protein interactions, and arginine hydrochloride is widely used as an additive in protein solutions because of its exceptional effects on protein association and folding. The molecular origins of arginine effects on protein processes remain, however, controversial, and little is known about the molecular interactions between arginine cations and protein surfaces in aqueous arginine solutions. In this study, we report a unique biochemical phenomenon whereby clusters of arginine cations (Arg(+)) are associated with a protein surface. The formation of protein-associated Arg(+) clusters is initiated by Arg(+) ions that associate with specific protein surface loci through cooperative interactions with protein guanidinium and carboxyl groups. Molecular dynamics simulations indicate that protein-associated Arg(+) ions subsequently attract other Arg(+) ions and form dynamic cation clusters that extend further than 10 Å from the protein surface. The effects of arginine on the thermal stability and size of lysozyme and ovalbumin are measured over a wide concentration range (0 to 2 M), and we find that the formation of protein-associated Arg(+) clusters consistently explains the complex effects of arginine on protein stability and size. This study elucidates the molecular mechanisms and implications of cluster formation of Arg(+) ions at a protein surface, and the findings of this study may be used to manipulate synthetic and biological systems through arginine-derived groups.

Comparative DFT Study To Determine if α-Oxoaldehydes are Precursors for Pentosidine Formation

We report a comprehensive density functional theory (DFT) study of the mechanism of pentosidine formation. This work is a continuation of our earlier studies in which we proposed pathways for formation of glucosepane (J. Mol. Model. 2011, pp 1-15, DOI 10.1007/s00894-011-1161-x), GODIC (glyoxal-derived imidazolium cross-link), and MODIC (methyl glyoxal-derived imidazolium cross-link; J. Phys. Chem. 2011, 115, pp 13542-13555). Here we show that formation of pentosidine via reaction of α-oxoaldehydes with lysine and arginine in aqueous solution is possible thermodynamically and kinetically, in good agreement with the available experimental evidence. Five pathways, A-E, were characterized, as in our previous GODIC and MODIC work. In pathways A and B, a Schiff base is first formed from lysine and methyl glyoxal (MGO), and this is followed by addition of arginine and glyoxal (GO). By contrast, in pathways C, D, and E, addition of arginine to MGO occurs first, resulting in the formation of imidazolone, which then reacts with lysine and GO to give pentosidine. Our calculations show that the reaction process is highly exergonic and that the three pathways A, C, and E are competitive. These results serve to underline the potentially important role that α-oxoaldehydes play as precursors in pentosidine formation in the complex field of glycation.

Enantioselective permeation of α-amino acid isomers through polymer membrane containing chiral metal–Schiff base complexes

Herein we report the preparation of thin film composite membranes containing metal complexes with chiral ligands, their characterization and performance evaluation for resolution of racemic amino acids. Schiff base complexes of Cu and Zn metals with chiral ligand were synthesized and cross-linked through amide linkage on polysulfone ultrafiltration membrane by in-situ interfacial polymerization reaction. The membranes were characterized using ATR-FTIR Spectroscopy, Scanning Electron Microscopy and Atomic Forced Microscopy. The permeability and enantiomers selectivity of the membranes were determined in pressure driven process at 1034.64kPa pressure using aqueous solutions of racemic lysine and arginine as feeds. The effects of permeation process parameters such as, concentration of feed and permeation time, on the performance of membranes were determined. Membranes permeated d-enantiomers of α-amino acids preferentially. Membrane containing Zn complex exhibited better enantioseparation compared to that containing Cu complex. Both of the membranes exhibited higher enantiomeric excess (ee, >94%) for d-lysine.

Preferential Interaction Coefficients of Proteins in Aqueous Arginine Solutions and Their Molecular Origins

Preferential interaction coefficients provide a thermodynamic measure to quantify the interactions between cosolutes and a protein. Preferential interactions of cosolutes can be measured experimentally using dialysis/densimetry and vapor pressure osmometry (VPO) techniques. The cosolute arginine is a widely used aggregation suppressor with a seemingly unique behavior. Its role in protein aggregation has been studied extensively, although a complete mechanistic understanding of its behavior is lacking. Moreover, due to experimental limitations, experimental preferential interaction data for arginine has only been reported at low concentrations. Schneider and Trout ( J. Phys. Chem. B 2009 , 113 , 7 ) have reported experimental preferential interaction data for argHCl (up to 0.7 m), and their study raised several interesting questions about the preferential interaction of arginine with proteins. Arginine is attracted to proteins at low concentrations but it was highly excluded at high concentrations. Furthermore, the preferential interaction coefficient values were found to vary as a square of the concentration, which is different from commonly observed linear relationship for other cosolutes like urea, glycerol, guanidinium hydrochloride, etc. In this study, preferential interaction coefficients of argHCl have been estimated computationally for two proteins (lysozyme and α-chymotripsinogen A) for a large concentration range (up to 2.8 m). On the basis of these results, the molecular level interactions responsible for the nonlinear exclusion of arginine from the protein surface are identified.