Olga I. Kalchenko

A comparative study of the determination of the stability constants of inclusion complexes of p-sulfonatocalix[4]arene with amino acids by RP-HPLC and 1H NMR

Reversed-phase high-performance liquid chromatography (Separon SGX C 18, UV detection at 254 nm and acetonitrile–water–trifluoroacetic acid (70∶30∶0.5, v/v), and methanol–water–trifluoroacetic acid (3∶97∶0.5, v/v) as mobile phases) was applied to the study of the host–guest complexation of p-sulfonatocalix[4]arene (SC[4]A) with amino acids as guests in the mobile phase. It was established that the formation of the inclusion complexes results in changes in the retention times of the amino acids. Stability constants of the complexes were determined. The variations in stability constants may be explained in terms of the various interactions (ion-pairing, hydrophobic, aromatic–aromatic and electrostatic interactions) that may occur between a given amino acid and SC[4]A. For the amino acids aspartic acid and proline the association constants were also derived from 1H NMR experiments.

Determination of the Stability Constants of Inclusion Complexes of p-H-37-(2-carboxy-methyloxy)-calix-[6]-arene and p-sulphonato-37-(2-carboxy-methyloxy)-calix-[6]-arene with 15 Amino acids by RP-HPLC

Reversed-phase high performance liquid chromatography (Separon SGX CN, UV detection at 254~nm and water as mobile phase) was applied to thestudy of the host–guest complexation ofp-H-37-(2-carboxy-methyloxy)-calix-[6]-arene (1) and p-sulphonato-37-(2-carboxy-methyloxy)-calix-[6]-arene (2)with 15 amino acids in the mobile phase. It was established that the formation ofthe inclusion complexes results in changes in the retention times and capacity factorsof amino acids. Stability constants of the complexes were determined. The variations instability constant values may be explained in terms of the different interactions, whichmay occur between amino acids and 1 and 2.

Calix[4]arene methylenebisphosphonic acids as inhibitors of fibrin polymerization

Calix[4]arenes bearing two or four methylenebisphosphonic acid groups at the macrocyclic upper rim have been studied with respect to their effects on fibrin polymerization. The most potent inhibitor proved to be calix[4]arene tetrakis‐methylene‐bis‐phosphonic acid (C‐192), in which case the maximum rate of fibrin polymerization in the fibrinogen + thrombin reaction decreased by 50% at concentrations of 0.52 × 10−6 m (IC50). At this concentration, the molar ratio of the compound to fibrinogen was 1.7 : 1. For the case of desAABB fibrin polymerization, the IC50 was 1.26 × 10−6 m at a molar ratio of C‐192 to fibrin monomer of 4 : 1. Dipropoxycalix[4]arene bis‐methylene‐bis‐phosphonic acid (C‐98) inhibited fibrin desAABB polymerization with an IC50 = 1.31 × 10−4 m. We hypothesized that C‐192 blocks fibrin formation by combining with polymerization site ‘A’ (Aα17–19), which ordinarily initiates protofibril formation in a ‘knob‐hole’ manner. This suggestion was confirmed by an HPLC assay, which showed a host–guest inclusion complex of C‐192 with the synthetic peptide Gly‐Pro‐Arg‐Pro, an analogue of site ‘A’. Further confirmation that the inhibitor was acting at the initial step of the reaction was obtained by electron microscopy, with no evidence of protofibril formation being evident. Calixarene C‐192 also doubled both the prothrombin time and the activated partial thromboplastin time in normal human blood plasma at concentrations of 7.13 × 10−5 m and 1.10 × 10−5 m, respectively. These experiments demonstrate that C‐192 is a specific inhibitor of fibrin polymerization and blood coagulation and can be used for the design of a new class of antithrombotic agents.

Complexation of Calix[4]arenephosphonous Acids with 2,4-Dichlorophenoxyacetic Acid and Atrazine in Water

Calix[4]arene phosphonous acids possessing two or four dihydroxyphosphoryl groups linked with the para-positions of the macrocyclic skeleton directly or by an aminomethyl spacer have been synthesised and their complexation with the herbicides2,4-dichlorophenoxyacetic acid (2,4-D) or atrazine (AT) in water has been investigated by the reversed phase HPLC method. The association constants of the 1 : 1 guest–host complexes of the herbicides (guest) with the calixarenes (host) in the range 772–5077 M-1 (2,4-D) and 2513–6785 M-1 (AT) have been determined from the relationship between the capacity factor of the guest and concentration of the calixarene host in the mobile phase. The association constants are dependent on the conformation and stereochemical mobility of the calixarene skeleton, the number of the dihydroxyphosphoryl groups at the upper rim, as well as the acid-base properties of the guest. Hydrophobic, electrostatic, and π-π-aromatic interactions in the guest–host complexes are discussed.

Symmetrical and inherently chiral water-soluble calix[4]arenes bearing dihydroxyphosphoryl groups

A series of symmetrical and inherently chiral water-soluble calix[4]arenes bearing one, two or four proton-ionisable dihydroxyphosphoryl groups at the narrow rim of the macrocycle has been synthesised by consecutive treatment of appropriate diethoxyphosphoryl derivatives with bromotrimethylsilane and methanol. The calix[4]arene phosphoric acids synthesised possess pKa-values 2.85–3.10 (CH3OH–H2O 70 : 30) and form salts with L-(−)-α-phenylethylamine or (1S,2R)-(+)-ephedrine in methanol solution. The salts of the inherently chiral calixarene phosphoric acids with chiral amines are easily separated into diastereomeric forms by the RP HPLC method on Separon SGX C18 or Partisil 5 ODS 3 achiral columns.

Study of the Complexation of Octakis(diethoxyphosphoryloxy)-tetramethylcalix[4]resorcinarene with Benzene Derivatives by the RP HPLC Method

Stability constants of the host–guest complexes of octakis(diethoxyphosphoryloxy) tetramethylcalix[4]resorcinarene (RA) with different benzene derivatives (alkyl benzenes, halogenated benzenes, substituted aldehydes, phenols and benzoic acids) were determined by the reversed phase high-performance liquid chromatography (RP HPLC) method (Separon SGX C 18, UV detector at 254 nm and acetonitrile-water, 86 : 14, v/v, as mobile phase) from the relationship between the aromatic guest capacity factors and the RA host concentration in the mobile phase. The constants are within the range 17–596 M−1, dependent on the size, nature, position and quantity of the substituents in the benzene ring of the guest molecules.

HPLC Study of Phosphorylcalixarene Complexation with Organic Substrates

Abstract Host–guest complexation of the calixarenes as well as thiacalixarenes bearing phosphoryl or sulfonate residues at the upper rim with a series of amino acids, uracils, adenines, and nucleotides (ADP and ATP) in water or water–organic solutions was investigated by high-performance liquid chromatography. Association constants of the 1:1 stoichiometry complexes were calculated from a ratio between the capacity factor of the guests and calixarene concentration in the mobile phase.

Complexation of calix[4]arenehydroxymethylphosphonic acids with amino acids. Binding constants determination of the complexes by HPLC method

Host–Guest complexation process of calixarenehydroxymethylphosphonic acids with 10 amino acids in solution H2O/MeCN (99:1) had been studied. Binding constants of the inclusion complexes from the dependence between capacity factors of the Guest and the calixarene-Host concentration in the mobile phase had been calculated. It was shown the binding constants depend on the nature of the amino acid residue, conformation of the calixarene skeleton, quantity of phosphoryl groups at the upper rim. In accordance with molecular calculation the complexation is determined by the electrostatic interactions between the positively charged nitrogen atom of amino acid and the negatively charged oxygen atom of phosphonic group of calixarene molecule, hydrogen bonds, π–π, CH–π and solvatophobic, interactions.

Supramolecular Chemistry of Phosphorus-Containing (Thia)Calixarenes

Molecular modeling, synthesis, and structural investigations of the phosphorus-containing (thia)calixarenes and their supramolecular complexes with biorelevant or ecologically hazardous molecules and ions are discussed within the context of cationic and molecular recognition, extraction properties, and bioactivity.

Synthesis of Calixarene-Methylenebisphosphonic Acids and Their Influence on Fibrin Polymerization

Abstract A series of hydroxycalix[4]arenes bearing one, two, or four fragments of methylenebisphosphonic acids was synthesized by the reaction of appropriate formylcalixarenes with sodium salts of dialkylphosphites. These calixarenes inhibit specifically 50% of fibrin polymerization in the fibrinogen + thrombin reaction as well as monomeric fibrin desAABB polymerization in concentration up to 0.5 × 10−6 M.