Calixarene Phosphonous Acids: Synthesis and Biological Activity

Abstract

The cone shaped сalix[4]arene hydroxyphosponous, ketophosphonous, methylenebisphosphonous, and hydroxymethylenebisphosphonous acids are specific inhibitors of glutathione S-transferase, ATPases of smooth muscle cells, fibrin polymerization processes     

Selective Recognition of Amino Acids and Peptides by Small Supramolecular Receptors

To this day, the recognition and high affinity binding of biomolecules in water by synthetic receptors remains challenging, while the necessity for systems for their sensing, transport and modulation persists. This problematic is prevalent for the recognition of peptides, which not only have key roles in many biochemical pathways, as well as having pharmacological and biotechnological applications, but also frequently serve as models for the study of proteins. Taking inspiration in nature and on the interactions that occur between several receptors and peptide sequences, many researchers have developed and applied a variety of different synthetic receptors, as is the case of macrocyclic compounds, molecular imprinted polymers, organometallic cages, among others, to bind amino acids, small peptides and proteins. In this critical review, we present and discuss selected examples of synthetic receptors for amino acids and peptides, with a greater focus on supramolecular receptors, which show great promise for the selective recognition of these biomolecules in physiological conditions. We decided to focus preferentially on small synthetic receptors (leaving out of this review high molecular weight polymeric systems) for which more detailed and accurate molecular level information regarding the main structural and thermodynamic features of the receptor biomolecule assemblies is available.     

Supramolecular Recognition of Amino Acids by Twisted Cucurbit[14]uril

Binding interactions between twisted cucurbit[14]uril (tQ[14]) and twenty standard amino acids (AAs) have been investigated by NMR spectroscopy and isothermal titration calorimetry (ITC) in aqueous HCl solutions and in DMSO. The results showed that tQ[14] displays clear binding affinity for AAs with a positively charged side chain or containing an aromatic ring, but weaker binding affinity for AAs with hydrophobic or polar side chains, with the binding mode depending on the type of side chain present in the AAs.     

Highly Stereoselective Recognition and Deracemization of Amino Acids by Supramolecular Self‐Assembly

The highly stereoselective supramolecular self‐assembly of α‐amino acids with a chiral aldehyde derived from binol and a chiral guanidine derived from diphenylethylenediamine (dpen) to form the imino acid salt is reported. This system can be used to cleanly convert D ‐amino acids into L ‐amino acids or vice versa at ambient temperature. It can also be used to synthesize α‐deuterated D ‐ or L ‐amino acids. A crystal structure of the ternary complex together with DFT computation provided detailed insight into the origin of the stereoselective recognition of amino acids.     

Complexation of thiacalix[4]arene methylphosphonic and sulphonic acids with amino acids

In this paper, host–guest complexation process of thiacalix[4]arene tetrakis–methylphosphonic and tetrakis–sulphonic acids with amino acids by HPLC and molecular modelling methods has been studied. It was shown that thiacalix[4]arene tetrakis–methylphosphonic acid due to transformability of macrocyclic skeleton and flexibility of methylphosphonic substituents can adopt its conformation for strong multicentre binding of the amino acids with association constant values 530–10,140 M^? 1 in water.     

Fluorimetric Analysis of Five Amino Acids in Chocolate: Development and Validation

Amino acids present ergogenic action, helping to increase, protect, and restore the muscular system of young athletes. Moreover, the encapsulation of five relevant amino acids in chocolate pellet form will appeal to them, facilitating their daily consumption. A reliable HPLC fluorimetric method was developed to detect and quantitatively determine L-Leucine, L-Isoleucine, L-Histidine, L-Valine, and β-Alanine in chocolate using aniline as an internal standard. Experimental design methodology was used to investigate and optimize the clean-up procedure of the samples. Therefore, three extraction techniques (solid-phase extraction (by two different SPE cartridges) and liquid–solid extraction (LSE)) were compared and evaluated. The LOQ values in chocolate varied from 24 to 118 ng/g (recovery 89.7–95.6%, %RSD < 2.5). Amino acids were pre-column derivatized with o-phthalaldehyde (OPA), while derivatization parameters were thoroughly investigated by experimental design methodology. The analysis was performed by HPLC-fluorescence (emission: λ = 455 nm, excitation: λ = 340 nm) method using a C₁₈ column and a mixture of phosphate buffer (pH = 2.8; 20 mM)-methanol as a mobile phase in gradient elution. The method was validated (r² > 0.999, %RSD < 2, LOD: 10 ng mL⁻¹ for histidine and leucine, 2 ng mL⁻¹ for alanine and valine, and 4 ng mL⁻¹ for Isoleucine) according to the International Conference on Harmonization guidelines.     

Synthesis,Characterization and Structure of Chiral Amino Acids and Their Corresponding Amino Alcohols with Camphoric Backbone

1 INTRODUCTION Chiral amino acids and their versatile derivatives are very useful compounds in many fields[1]. In com- parison with well-documented chiral α and β amino acids and amino alcohols, the studies of chiral γ, δ… ω amino acids and amino alcohols deserve more attention. For example, there have been numerous reports on versatile functions of γ aminobutyric acid (GABA) produced from L-glutamic acid in the presence of L-glutamate decarboxylase (GAD)[2]. However, the stereo…     

A ChemiluminesClent Precolumn Labelling Reagent for High-Performance Liquid Chromatography of Amino Acids

Abstract

A chemiluminescent tag for precolumn derivatization of amino acids has been developed. The tag, 4-isocyanatophthalhydrazide, couples with 17 amino acids tested, including proline and hydroxyproline, in less than ten minutes. Twelve derivatized amino acids have been separated and detected with an average detection limit of 10 femptomoles per 20 μL injection.     

Benzylidene Acetal Protecting Group as Carboxylic Acid Surrogate: Synthesis of Functionalized Uronic Acids and Sugar Amino Acids

Direct oxidation of the 4,6‐O‐benzylidene acetal protecting group to C‐6 carboxylic acid has been developed that provides an easy access to a wide range of biologically important and synthetically challenging uronic acid and sugar amino acid derivatives in good yields. The RuCl₃–NaIO₄‐mediated oxidative cleavage method eliminates protection and deprotection steps and the reaction takes place under mild conditions. The dual role of the benzylidene acetal, as a protecting group and source of carboxylic acid, was exploited in the efficient synthesis of six‐carbon sialic acid analogues and disaccharides bearing uronic acids, including glycosaminoglycan analogues.     

Simple Synthesis of Ruthenium π Complexes of Aromatic Amino Acids and Small Peptides

The interaction of [Ru(η⁶‐C₁₀H₈)(Cp)]⁺ (Cp=C₅H₅) with aromatic amino acids (L ‐phenylalanine, L ‐tyrosine, L ‐tryptophane, D ‐phenylglycine, and L ‐threo‐3‐phenylserine) under visible‐light irradiation gives the corresponding [Ru(η⁶‐amino acid)(Cp)]⁺ complexes in near‐quantitative yield. The reaction proceeds in air at room temperature in water and tolerates the presence of non‐aromatic amino acids (except those which are sulfur containing), monosaccharides, and nucleotides. The complex [Ru(η⁶‐C₁₀H₈)(Cp)]⁺ was also used for selective labeling of Tyr and Phe residues of small peptides, namely, angiotensin I and II derivatives.     

Analysis of Free Amino Acids and Protein Contents of Mature Human Milk from Turkish Mothers

Abstract

This study was designed to evaluate free amino acid (FAA) composition and total protein in mature human milk from Turkish mothers. Free amino acid concentrations in mature human milk were determined in all subjects using a high‐performance liquid chromatography (HPLC) with postcolumn derivatization system, with a fluorescence detector. Total protein content was determined by the classical biuret method. Total protein concentration was found to be 1.3±0.4 mg/dl. Glutamic asid plus glutamine is the most abundant amino acid (1275 µmol/L), followed by taurine (353 µmol/L) and alanine (261 µmol/L). Glutamic acid plus glutamine accounts for the most free amino acids in mature human milk and their sum represents 40% of total FAA. On the other hand, some amino acid derivatives such as citrulline, ethanolamine, ammonium, ornithine, ortophosphoserine, and phosphoethanolamine, not usually a part of protein, are determined and this fraction represented ～21% of the total FAA in mature human milk in the present study.     

Complexation of Some Amino Acids and Peptides by p-Sulfonatocalix[4]arene and Hexasodium p-Sulfonatocalix[6]arene in Aqueous Solution

The stability constants (log K), the reaction enthalpy( H) and entropy ( S) of the complexesformed between some amino acids (glycine, L-alanine,L-valine, L-leucine, L-phenylalanine, L-tryptophan,L-threonine, and L-lysine) and peptides (glycyl-glycine,glycyl-L-alanine, glycyl-L-leucine, glycyl-L-phenylalanine,L-leucyl-glycine, L-leucyl-L-alanine, glycyl-L-valine,L-leucyl-glycyl-glycine, and glycyl-glycyl-glycine) withp-sulfonatocalix[4]arene and hexasodiump-sulfonatocalix[6]arene in aqueous solutions by meansof calorimetric titration have been investigated. The reportedresults demonstrate that the amino acids and peptides under studyform complexes with both p-sulfonatocalix[4]areneand hexasodium p-sulfonatocalix[6]arene. In the case of theamino acids and peptides the complexation with water-solublecalixarenes in aqueous solution is favored by enthalpiccontributions and disfavored by entropic contributions. However,no influence of the ring size of the calixarenes upon thecomplexation is observed. By comparison with the reaction ofthe sodium salt of phenol-4-sulfonic acid with amino acids amacrocyclic effect in case of the calixarenes is possible.     

Electronic and ESR Spectra of Copper(II) Complexes with N,N-Dialkyl Amino Acids

Five N,N-dialkylamino acids were synthesised [4]: N,N-dimethylisoleucine (DMIL), N,N-dimethyl-alloisoleucine (DMAIL), N,N-dimethylvaline (DMV), N,N-diethyl-alanine (DEA), and N,N-diethylvaline (DEV), as well as their complexes with copper(II): Cu(DMIL)₂, Cu(DMAIL)₂, Cu(DMV)₂, Cu(DMIL)(DMV), Cu(DEA)₂, and Cu(DEV)₂. UV/VIS spectra of the complexes were recorded in CH₂Cl₂ solutions and the ESR spectra in CH₂Cl₂, CD₃OD, and D₂O solutions. By applying the analysis of variance, ESR spectra were shown to be influenced by the solvent and substituent differences, the former effect being related to the degree of covalency of the copper-ligand bonds. The effect of the ligand's spatial configuration (diastereoisomerism) upon the ESR spectrum of the complex was demonstrated and explained.     

Green Synthesis of new Trizole Based Heterocyclic Amino Acids Ligands and their Transition Metal Complexes. Characterization,Kinetics, Antimicrobial and Docking Studies

Two novel amino acids imine ligands (H₂L₁ and H₂L₂) have been synthesized using green condensation reaction from 2‐[3‐Amino‐5‐(2‐hydroxy‐phenyl)‐5‐methyl‐1,5‐dihydro‐[1, 2, 4]triazol‐4‐yl]‐3‐(1H‐indol‐3‐yl)‐propionic acid with benzaldehyde/p‐flouro benzaldehyde (1:1 molar ratio) in the presence of lemon juice as a natural acidic catalyst in aqueous medium. Their transition metal complexes have been prepared in a molar ratio (1:1). Characterization of the ligands and complexes using elemental analysis, spectroscopic studies, ¹HNMR, ¹³CNMR, and thermal analysis has been reported. E*, ΔH*, ΔS* and ΔG* thermodynamic parameters, were calculated to throw more light on the nature of changes accompanying the thermal decomposition process of these complexes. The molar conductance measurement of metal complexes showed nonelectrolyte behavior. The metal complexes of the two ligands have tetrahedral geometry with a general molecular structure [M(H₂L)X_n], where [(M = Mn (II), Co (II), Cu (II) and Zn (II), X = Cl, n = 2]; M = VO (II), X = SO₄, n = 1] for H₂L₁. [M = Co (II), Cu (II), Zn (II)] for H₂L₂. Antibacterial activity of the complexes against (Bacillis subtilis, Micrococcus luteus, Escherichia coli), also antifungal activity against (Aspergillus niger, Candida Glabarta, Saccharomyces cerevisiae) have been screened. The results showed that all complexes have antimicrobial activity higher than free ligands. Molecular docking studies results showed that, all the synthesized compounds having minimum binding energy and have good affinity toward the active pocket, thus, they may be considered as good inhibitor of targeting PDB code: 1SC7 (Human DNA Topo‐isomerase I).     

Synthesis and Structure of an Octopus-like Octapropargyl Tetra-iso-butyl-resorcin[4]arene

1 INTRODUCTION Resorcin[4]arene is a cyclic tetramer and can be easily obtained by acid-catalyzed condensation of resorcinol with a variety of aldehydes. The all-cis isomer with crown C4v symmetry is mostly isolated by means of alkyl aldehydes[1]. They have been used as starting materials for the synthesis of cavitands, velc-rands, and even more complex compounds like carce-rands, hemicarceracnds, and holands[2～4]. Of the ob-vious places for the chemical modification of reso-rcin[4]arene…     

A Facile Synthesis of N-Phosphoryl Amino Acids Containing Hydroxy Group

three kinds of N-(diisopropyloxyphosphoryl) amino acids containing hydroxyl group were prepared in high yield by using diisopropyl phosphite as the phosphorylating agent, sodium hypochlorite as the chlorinating agent and tetrabutyl ammonium bromide as the phase transfer catalyst in basic aqueous media.     

Potential Iwternal Standards for the Reversed-Phase High Performance Liquid Chromatography Analysis of Thyroidal Amino Acids

Abstract

Seven analogs of DL-thyroxine (1) were synthesized and evaluated as internal standards for the reversed-phase HPLC analysis of thyroidal amino acids. On the basis of retention time, separation from DL-thyroxine (1), stability, solubility and ease of preparation, 3-[3-(4′-hydroxy-3′,5′-diiodophenoxy)-2,4,6-triiodophenyl)]-DL-alanine (4) appeared to be the best candidate for use as an internal standard.