Glutamic Acid Complexes Research Articles

Evaluation of an experimental bio-nutrient feedlot premix on health, growth performance, carcass merit, and prevalence and severity of liver abscesses in feedlot cattle managed under a natural feeding protocol

This research evaluates the efficacy of an experimental diet premix on growth performance, carcass traits, liver abscesses, lung lesions, and health of naturally raised feedlot cattle. A randomized complete block design trial was conducted at a commercial feedlot using 32 pens of steers and heifers (initial BW = 382 kg) and fed an average of 223 d. Antimicrobials, medicated feed additives, or growth-promoting implants were not administered. Treatments included (1) standard diets (CON) and (2) standard diets including a premix (TST) providing lysine and glutamic acid complexes of zinc and manganese, cobalt pectinate, organic iodine (ethylenediamine dihydroiodide), and rumen protected folate. Mortality rate was not affected (P = 0.68) by treatment. Removal for respiratory issues and the natural program fallout rate were greater (P < 0.01) for TST cattle compared with CON. Control cattle had greater DMI, final BW, ADG, and carcass weight (P ≤ 0.05) compared with TST. Control cattle had greater G:F than TST cattle when deads and fallouts were included (P = 0.02), but not when deads and fallouts were excluded (P = 0.92). Percentage carcasses qualifying for each USDA quality grade category did not differ between treatments (P ≥ 0.07). No treatment differences were observed for the percentage of abscessed livers (P = 0.62) or for the percentage of cattle with lung lesions (P = 0.51). The TST diet premix evaluated did not improve growth performance, carcass merit, or feedlot health attributes under the conditions of this study.

Amino Acid Complexes of Zirconium in a Carbon Composite for the Efficient Removal of Fluoride Ions from Water.

Amino acid complexes of zirconia represent an entirely new class of materials that were synthesized and studied for the first time for the decontamination of fluoride ion containing aqueous solutions. Glutamic and aspartic acid complexes of zirconia assembled with thin carbon (stacked graphene oxide) platelets deriving from graphite oxide (GO) were synthesized by a two-step method to prepare adsorbents. The characterization of the complexes was carried out using infrared spectroscopy to determine the functional groups and the types of interaction between the composites and fluoride ions. To reveal the mechanisms and extent of adsorption, two types of batch adsorption measurements were performed: (i) varying equilibrium fluoride ion concentrations to construct adsorption isotherms at pH = 7 in the absence of added electrolytes and (ii) using fixed initial fluoride ion concentrations (10 mg/L) with a variation of either the pH or the concentration of a series of salts that potentially interfere with adsorption. The experimental adsorption isotherms were fitted by three different theoretical isotherm equations, and they are described most appropriately by the two-site Langmuir model for both adsorbents. The adsorption capacities of Zr-glutamic acid-graphite oxide and Zr-aspartic acid-graphite oxide are 105.3 and 101.0 mg/g, respectively. We found that two distinct binding modes are combined in the Zr-amino acid complexes: at low solution concentrations, F− ions are preferentially adsorbed by coordinating to the surface Zr species up to a capacity of ca. 10 mg/g. At higher concentrations, however, large amounts of fluoride ions may undergo anion exchange processes and physisorption may occur on the positively charged ammonium moieties of the interfacially bound amino acid molecules. The high adsorption capacity and affinity of the studied dicarboxylate-type amino acids demonstrate that amino acid complexes of zirconia are highly variable materials for the safe and efficient capture of strong Lewis base-type ions such as fluoride.

The Value of Monomer Hydrogen Proton Magnetic Resonance Spectra in the Diagnosis of Liver Benign and Malignant Lesions

The early diagnosis and treatment of liver disease are very important in clinics. Magnetic resonance spectroscopy (MRS) provides a non-invasive 'window' on the biochemical processes in the body. This study deployed research based on application of monomer element 1HMRS in the diagnosis of benign or malignant liver lesions. Patients with different liver diseases were recruited along with healthy controls. GE Signa Twinspeed 1.5T MRI was performed on livers along with monomeric hydrogen MRS, followed by SAGE software analysis. In healthy patient's livers, both choline and lipid peaks were observed under MRS, with occasionally glutamine and glutamic acid complex (Glx) peak and glucogen and glucose complex (Glu) peak. Malignant liver lesions had significantly elevated choline peak and choline/lipid ratio compared to control or benign lesions (P &lt; 0.05). The accuracy, sensitivity and specificity of MRI against malignant tumors were 89.4%, 86.2% and 91.1%, respectively. These figures for choline/lipid and MRI plus choline/lipid were 87.2%, 92.3% and 90.1%, and 94.1%, 89.1% and 90.4%, respectively. Our study shows that monomeric hydrogen proton MRS might be used as the diagnostic evidences for malignant liver diseases, especially for choline peak level and choline/lipid ratio. However, large cohort multi-center study is required to confirm the findings in the future.

A redetermination of the crystal structure of the mannitol complex NH4[Mo2O5(C6H11O6)]·H2O: hydrogen-bonding scheme and Hirshfeld surface analysis.

The redetermined structure [for the previous study, see: Godfrey & Waters (1975 ▸). Cryst. Struct. Commun. 4, 5-8] of ammonium μ-oxido-μ-[1,5,6-tri-hydroxy-hexane-2,3,4-tris-(olato)]bis-[dioxidomolybdenum(V)] monohydrate, NH4[Mo2(C6H11O6)O5]·H2O, was obtained from an attempt to prepare a glutamic acid complex from the [Co2Mo10H4O38]6- anion. Subsequent study indicated the complex arose from a substantial impurity of mannitol in the glutamic acid sample used. All hydrogen atoms have been located in the present study and the packing displays N-H⋯O, O-H⋯O and C-H⋯O hydrogen bonds. A Hirshfeld surface analysis was also performed.

Targeted PEG-poly(glutamic acid) complexes for inhalation protein delivery to the lung

Pulmonary delivery is increasingly seen as an attractive, non-invasive route for the delivery of forthcoming protein therapeutics. In this context, here we describe protein complexes with a new ‘complexing excipient’ - vitamin B12-targeted poly(ethylene glycol)-block-poly(glutamic acid) copolymers. These form complexes in sub-200nm size with a model protein, suitable for cellular targeting and intracellular delivery. Initially we confirmed expression of vitamin B12-internalization receptor (CD320) by Calu-3 cells of the in vitro lung epithelial model used, and demonstrated enhanced B12 receptor-mediated cellular internalization of B12-targeted complexes, relative to non-targeted counterparts or protein alone. To develop an inhalation formulation, the protein complexes were spray dried adopting a standard protocol into powders with aerodynamic diameter within the suitable range for lower airway deposition. The cellular internalization of targeted complexes from dry powders applied directly to Calu-3 model was found to be 2–3 fold higher compared to non-targeted complexes. The copolymer complexes show no complement activation, and in vivo lung tolerance studies demonstrated that repeated administration of formulated dry powders over a 3 week period in healthy BALB/c mice induced no significant toxicity or indications of lung inflammation, as assessed by cell population count and quantification of IL-1β, IL-6, and TNF-α pro-inflammatory markers. Importantly, the in vivo data appear to suggest that B12-targeted polymer complexes administered as dry powder enhance lung retention of their protein payload, relative to protein alone and non-targeted counterparts. Taken together, our data illustrate the potential developability of novel B12-targeted poly(ethylene glycol)-poly(glutamic acid) copolymers as excipients suitable to be formulated into a dry powder product for the inhalation delivery of proteins, with no significant lung toxicity, and with enhanced protein retention at their in vivo target tissue.

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

Complexes of glutamic acid (Glu) cationized with Zn2+ and Cd2+ were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy using light generated from a free electron laser. Complexes of deprotonated Glu with Zn2+, [Zn(Glu-H)ACN]+ (where ACN = acetonitrile, CH3CN), and intact Glu with CdCl+, CdCl+(Glu) were formed. Notably, photodissociation induces Glu fragmentation rather than ACN loss in the Zn2+ complex. In order to identify the structures formed experimentally, the experimentally obtained spectra were compared to those calculated from optimized structures at the B3LYP/6-311+G(d,p) level for [Zn(Glu-H)ACN]+ and B3LYP/def2-TZVP level with an SDD effective core potential on cadmium for the CdCl+(Glu) system. The main binding motif observed for the heavy metal complex is a charge solvated, tridentate [N,COs,CO] structure where the metal binds to the backbone amino group and carbonyl oxygens of the side-chain and backbone carboxylic acid groups. The Zn2+ system similarly prefers a [N,CO-,COs] binding motif, where binding is observed at one oxygen of the backbone carboxylate site along with the backbone amino and side-chain carbonyl groups. In both cases, the theoretically determined lowest-energy conformers explain the experimental [Zn(Glu-H)ACN]+ and CdCl+(Glu) spectra well.

Correction: Experimental and theoretical investigations of infrared multiple photon dissociation spectra of glutamic acid complexes with Zn2+ and Cd2.

Correction for 'Experimental and theoretical investigations of infrared multiple photon dissociation spectra of glutamic acid complexes with Zn2+ and Cd2+' by Georgia C. Boles et al., Phys. Chem. Chem. Phys., 2017, 19, 12394-12406.

Tunable Aggregation-Induced Emission of Polyoxometalates via Amino Acid-Directed Self-Assembly and Their Application in Detecting Dopamine

In this work, through the aqueous phase self-assembly of an Eu-containing polyoxometalate (POM), Na9[EuW10O36]·32H2O (EuW10) and different amino acids, we obtained spontaneously formed vesicles that showed luminescence enhancement for EuW10 and arginine (Arg), lysine (Lys), or histidine (His) complexes, but luminescence quenching for EuW10 and glutamic acid (Glu) or aspartic acid (Asp) complexes. The binding mechanisms between them have been explored at the molecular level by using different characterization techniques. It was found that EuW10 acted as polar head groups interact with the positively charged residues for alkaline amino acids, protonated amide groups for acidic amino and nonpolar acid aminos through electrostatic interactions, and the remaining segments of amino acids served as relatively hydrophobic parts aggregated together forming bilayer membrane structures. Moreover, the different influences of amino acids on the fluorescence property of EuW10 revealed that the electrostatic interaction between the positive charged group of amino acid and the polyanionic cluster dominates the fluorescence properties of assemblies. Furthermore, a turn-off sensing application of the EuW10/Arg platform to probe dopamine (DA) against various other biological molecules such as neurotransmitters or amino acids was also established. The concept of combining POMs with amino acids extends the research category of POM-based functional materials and devices.

Oxidation mechanism of molecular oxygen over cyclohexene catalyzed by a cobaltl-glutamic acid complex

We introduce a new strategy towards the cyclohexene oxidation reaction, which is driven by molecular oxygen with a cobalt(ii)/amine acid complex as the catalyst without any solvents.

Feasibility of Antibody–Poly(Glutamic Acid) Complexes: Preparation of High-Concentration Antibody Formulations and Their Pharmaceutical Properties

Development of high-concentration antibody formulations for subcutaneous administration remains challenging. Recently, a precipitation-redissolution method was proposed to prepare suspensions or precipitates of salt-dissociable protein-poly(amino acid) complexes. To elucidate the utility of this method for protein therapy, we investigated the feasibility of a precipitation-redissolution method using poly(amino acid) for high-concentration antibody formulation. Omalizumab and adalimumab formulations of 150 mg/mL could be prepared using poly-l-glutamic acid (polyE) from low-concentration stock solutions. Enzyme-linked immunosorbent assay, circular dichroism, and size-exclusion chromatography revealed that the formation of antibody-polyE complex and precipitation-redissolution process did not significantly affect the immunoreactivity or secondary structure of the antibodies. The precipitation-redissolution method was less time-consuming and more effective than lyophilization-redissolution, evaporation-redissolution, and ultrafiltration from the viewpoint of final yield. Scalability was confirmed from 400 μL to 1.0 L. The general toxicity and pharmacokinetic profiles of the antibody-polyE complex formulations were similar to those of conventional antibody formulations. These results suggested that the precipitation-redissolution method using poly(amino acid) has great potential as a concentration method for antibody formulation and medicinal use.

Biocompatibility of novel carboxylated graphene oxide–glutamic acid complexes

The biocompatibility improvement of graphene oxide is crucial for biomedical applications. Herein, we propose to prepare carboxylated graphene oxide (GeneO–COOH) with glutamic acid (Glu) at different pH values. The complexes (GemeO–COOH/Glu) are characterized by FT-IR, XRD, TG, and Zeta potential. The results show that the complexes have close relation with pH value due to the acid-responsive Glu. It is demonstrated that GeneO–COOH complexes with Glu via amidation reaction in the basic domain. The blood compatibility of GeneO–COOH/Glu complexes is evaluated by hemolysis and recalcification test. The results show that the plasma recalcification time is prolonged greatly in the whole blood, and the hemolysis rates are less than 5 %. In a word, GeneO–COOH/Glu complexes are blood compatible at low concentration, which is potential for producing blood-contacting materials.

Synergistic Activities of a Silver(I) Glutamic Acid Complex and Reactive Oxygen Species (ROS): A Novel Antimicrobial and Chemotherapeutic Agent

The antimicrobial and chemotherapeutic activities of a silver(I) glutamic acid complex with the synergistic concomitant generation of reactive oxygen species (ROS) were investigated here. The ROS generation system employed was via Fenton chemistry. The antimicrobial and chemotherapeutic activities were investigated on Staphylococcus aureus ATCC 43300 and Escherichia coli bacteria, and Vero and MCF-7 tumor cell lines, respectively. Antimicrobial activities were conducted by determining minimum inhibitory concentration (MIC), while chemotherapeutic efficacies were done by serial dilution using standard techniques to determine the half maximal inhibitory concentration (IC50). The antimicrobial and chemotherapeutic results obtained were compared with positive control drugs gentamicin, oxacillin, penicillin, streptomycin and cisplatin, a ubiquitously used platinum-based antitumor drug, and with the silver(I) glutamic acid complex and hydrogen peroxide separately. Based on MIC and IC50 values, it was determined that this synergistic approach was very effective at extremely low concentrations, especially when compared with the other drugs evaluated here. This finding might be of great significance regarding metronomic dosing when this synergistic approach is clinically implemented. Since silver at low concentrations exhibits no toxic, mutagenic and carcinogenic activities, this might offer an alternative approach for the development of safer silver-based antimicrobial and chemotherapeutic drugs, thereby reducing or even eliminating the toxicity associated with current drugs. Accordingly, the present approach might be integrated into the systemic clinical treatment of infectious diseases and cancer.

Effects of nonionic micellar aggregates on the electron transfer reaction between l‐glutamic acid and gold(III) complexes

AbstractThe effect of nonionic micelles of Triton X‐100 on the oxidative decarboxylation of l‐glutamic acid by chloroaurate(III) complexes has been investigated in acetate buffer medium. The reaction is first order with respect to Au(III), but a complex order with respect to glutamate. H+ ion has both accelerating and retarding effects in the pH range 3.72–4.80, whereas a Cl− ion has an inhibiting effect in the range 0.02–0.56 mol dm−3. Under the experimental conditions, AuCl−4 and AuCl3(OH)− are the predominant and effective oxidizing species, whereas the zwitterion (H2A) and mononegative anion (HA−) are the predominant reducing species of the amino acid. The reaction involves a one‐step two‐electron transfer process and passes through the intermediate formation of iminic cation. In the presence of surfactant, the reaction passes through a maximum and it appears to follow Berezin's model, where both the oxidant and the substrate are partitioned between the aqueous and the micellar phase and then react. The binding constants between the reactants and the surfactant have been evaluated at different temperatures. Compensation between substrate–water interaction and substrate–micelle interaction plays an important role in such redox reactions in the presence of a surfactant. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 482–493, 2012

A Zinc(II)/Poly(γ‐glutamic acid) Complex as an Oral Therapeutic for the Treatment of Type‐2 Diabetic KKAy Mice

In developing new insulin-mimetic zinc(II) complexes with various ligands including a biodegradable polymer, we prepared and characterized a Zn(gamma-pga) complex in solution as well as in solid, and investigated its in vitro insulin-mimetic activity and in vivo antidiabetic effect in type-2 diabetic KKA(y) mice. The in vitro insulin-mimetic activity of the Zn(gamma-pga) complex was considerable better than that of ZnSO(4). The Zn(gamma-pga) complex normalized the hyperglycemia in KKA(y) mice within 21 d when administrated orally at doses of 10-20 mg (0.15-0.31 mmol) Zn per kg body mass for 30 d. In addition, the impaired glucose tolerance, elevated HbA(1c) levels and metabolic syndromes were significantly improved in Zn(gamma-pga)-treated KKA(y) mice relative to those administrated with saline and ZnSO(4).

Specific interactions between diphenhydramine and α-helical poly(glutamic acid) – A new ion-pairing complex for taste masking and pH-controlled diphenhydramine release

Formation of drug/excipient complex through ionic interactions has proven to be very effective for both controlled release and taste masking. Unfortunately, the ionic interactions between drugs and small molecule excipients are usually weak, and the stability of the formed complexes can be greatly influenced by solution ionic strength. In this study, we explored to formulate diphenhydramine (DPH), a very bitter tasting drug, using small molecular weight and carboxyl group containing polymers. Studies showed that DPH interacted with α-helical poly(glutamic acid) specifically to produce DPH/poly(glutamic acid) complexes, mostly spherical in shape with a diameter of around 1.0 μm. Other drugs with similar chemical structures as DPH, such as phenylephrine and pseudoephedrine, could not form complexes with poly(glutamic acid) or other polymers under the same conditions. Although DPH in DPH/poly(glutamic acid) complexes existed amorphously, it showed increased stability. In vitro studies using electronic tongue demonstrated that poly(glutamic acid) might be as effective as sucralose for DPH bitter taste blocking. In addition, DPH/poly(glutamic acid) complexes were not stable in neutral or weak acidic (pH > 5) environments and dissolved rapidly and completely. Therefore, DPH/poly(glutamic acid) complex may serve as a new formulation for taste masking and controlled DPH release in gastrointestinal tract. This is the first report that small molecule drugs can interact with peptides of specific secondary structures to form stable complexes. In addition to greatly expanded ion-pairing excipient pool, application of peptides in drug formulation may also solve the selectivity and stability problems faced by current small molecule excipients.

Partial Agonism and Antagonism of the Ionotropic Glutamate Receptor iGLuR5: STRUCTURES OF THE LIGAND-BINDING CORE IN COMPLEX WITH DOMOIC ACID AND 2-AMINO-3-[5-tert-BUTYL-3-(PHOSPHONOMETHOXY)-4-ISOXAZOLYL]PROPIONIC ACID

More than 50 structures have been reported on the ligand-binding core of the ionotropic glutamate receptor iGluR2 that belongs to the 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid-type of receptors. In contrast, the ligand-binding core of the kainic acid-type receptor iGluR5 has only been crystallized with three different ligands. Hence, additional structures of iGluR5 are needed to broaden the understanding of the ligand-binding properties of iGluR5, and the conformational changes leading to channel opening and closing. Here, we present two structures of the ligand-binding core of iGluR5; one as a complex with the partial agonist (2S,3S,4S)-3-carboxymethyl-4-[(1Z,3E,5R)-5-carboxy-1-methyl-hexa-1,3-dienyl]-pyrrolidine-2-carboxylic acid (domoic acid) and one as a complex with the antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid ((S)-ATPO). In agreement with the partial agonist activity of domoic acid, the ligand-binding core of the iGluR5 complex is stabilized by domoic acid in a conformation that is 11 degrees more open than the conformation observed in the full agonist (S)-glutamic acid complex. This is primarily caused by the 5-carboxy-1-methyl-hexa-1,3-dienyl moiety of domoic acid and residues Val685-Thr690 of iGluR5. An even larger domain opening of 28 degrees is introduced upon binding of the antagonist (S)-ATPO. It appears that the span of domain opening is much larger in the ligand-binding core of iGluR5 (30 degrees) compared with what has been observed in iGluR2 (19 degrees ). Similarly, much larger variation in the distances between transmembrane linker residues in the two protomers comprising the dimer is observed in iGluR5 as compared with iGluR2.

Ionic Complexes of Biosynthetic Poly(malic acid) and Poly(glutamic acid) as Prospective Drug‐Delivery Systems

The hydrolytic degradability and erythromycin release from stoichiometric ionic complexes of biotechnological poly(beta,L-malic acid)s and poly(gamma,D-glutamic acid)s with alkyltrimethylammonium surfactants were investigated. The influence of pH, temperature and antibiotic load on hydrolysis rate was examined. It was found that poly(malic acid) complexes degraded by a surface erosion mechanism at a higher rate than poly(glutamic acid) complexes, which eroded in bulk. Erythromycin was lodged in the paraffinic subphase of the complexes and upon aging it was delivered according to a sigmoidal profile that appeared to be independent on the antibiotic load.

Investigation of a CuII–Poly(γ‐Glutamic Acid) Complex in Aqueous Solution and its Insulin‐Mimetic Activity

The complexation between cupric ions (Cu(II)) and poly(gamma-glutamic acid) (gamma-PGA) in aqueous solutions (pH 3-11) has been studied by UV-visible absorption and electron spin resonance (ESR) techniques. Formation of the Cu(II)-gamma-PGA complex is confirmed by the observation of the blue shift of the absorption band in the visible region, anisotropic line shapes in the ESR spectrum at room temperature, and a computer simulation of the visible absorption spectrum of the complex. The structure of the Cu(II)-gamma-PGA complex, depending on the pH, has been determined. The in vitro insulin-mimetic activity of the Cu(II)-gamma-PGA complex is examined by determining both inhibition of free fatty acid release and glucose uptake in isolated rat adipocytes treated with epinephrine, in which the concentration of the Cu(II)-gamma-PGA complex for 50% inhibition of free fatty acid release is very similar to that of CuSO4. However, it is significantly lower than that of a previously reported insulin-mimetic bis(3-hydroxypicolinato)copper(II), [Cu(3hpic)2], complex.

A modified equation for the calculation of the stability constants of W(VI)–NTA, Mo(VI)–NTA and Mo(VI)–glutamic acid complexes at different ionic strengths

The equilibria between molybdenum(VI) and tungsten(VI) with nitrilotriacetic acid (NTA) and glutamic acid are studied in aqueous solution at 25 °C and different ionic strengths ranging from (0.1 to 1.0) mol dm − 3 (NaClO 4). Stoichiometry and stability of the complexes formed are determined from a combination of potentiometric, polarimetric and spectrophotometric measurements. Tungsten(VI) forms a mononuclear complex with NTA of the type (WO 3L 3−) at pH = 7.5. The complexation of molybdenum(VI) with nitrilotriacetic acid and glutamic acid occurs at pH = 6.0. By introducing two empirical parameters C and D in these three complex formation reactions the dependence of the dissociation and stability constants on ionic strength is described by a Debye–Huckel type equation. Finally a comparison has been made between the calculated and experimental values of stability constants.

Antidiabetic and Anticoagulant Properties of Heparin–Glutamic Acid Complex

Natural heparin complexes proved to activate the anticoagulation system. The obtained experimental data convincingly confirm that glutamic acid alone, and particularly in a complex with heparin, has a considerable preventive potential and efficiently protects experimental animals with induced diabetes mellitus.