Adam Buczkowski

Interaction between PAMAM-NH2 G4 dendrimer and 5-fluorouracil in aqueous solution

The formation equilibrium of poly(amidoamine) dendrimer (PAMAM-NH₂ G4) complex with an oncologic drug such as 5-fluorouracil (5-FU) in water at room temperature was examined. Using the results of the drug solubility in dendrimer solutions and the method of equilibrium dialysis, the maximal number of drug molecules in the dendrimer-drug complex and its equilibrium constant were evaluated. Solubility results show that PAMAM-NH₂ G4 dendrimer can transfer tens 5-fluorouracil molecules in aqueous solution. The number of active sites in a dendrimer macromolecule being capable of combining the drug, determined by the separation method, amounts to n=30 ± 4. The calculated equilibrium constant of the 5-FU-active site bonding is equal to K=(400 ± 120).

Thermochemical and spectroscopic studies on the supramolecular complex of PAMAM-NH2 G4 dendrimer and 5-fluorouracil in aqueous solution

The equilibrium of the formation of polyamidoamine dendrimer (PAMAM-NH(2) G4) and an oncological drug, 5-fluorouracil (FU) in water at room temperature has been examined. Using calorimetric titration, the number of active sites in the dendrimer combining the drug molecules and the equilibrium constant of the dendrimer-drug complex were estimated. The addition of the drug to the dendrimer active sites is an exothermic process. This process is accompanied by a beneficial change in entropy. The number of drug molecules combined by the polymer was confirmed by means of (1)H NMR spectroscopy. (1)HNMR measurements show that the dendrimer macromolecule binds the drug molecules with superficial protonated or unprotonated amine groups.

Interaction of polyamidoamine (PAMAM) succinamic acid dendrimers generation 4 with human serum albumin

Dendrimers, a relatively new group of highly branched three dimensional polymers, are intensively investigated to use them in biomedical and physicochemical sciences. Their specific architecture gives them the ability to interact with many different types of molecules. In our studies the interaction between PAMAM succinamic acid dendrimers generation 4 (PAMAM-SAH G4) and human serum albumin (HSA) was examined. Experiments showed that a single molecule of a HSA can bind approximately 6 particles of dendrimers. The fluorescence studies demonstrated that dendrimers lead to a decrease in protein fluorescence but changes in fluorescence anisotropy were not observed. Alterations in the spectrum of circular dichroism indicated changes in the secondary protein structure. The results clearly show that this generation of dendrimers possesses a strong ability to interact with human serum albumin.

Spectroscopic and calorimetric studies of formation of the supramolecular complexes of PAMAM G5-NH2 and G5-OH dendrimers with 5-fluorouracil in aqueous solution

The results of spectroscopic measurements (increase in solubility, equilibrium dialysis, (1)H NMR titration) and calorimetric measurements (isothermal titration ITC) indicate exothermic (ΔH<0) and spontaneous (ΔG < 0) combination of an antitumor drug, 5-fluorouracil, by both cationic PAMAM G5-NH2 dendrimer and its hydroxyl analog PAMAM G5-OH in aqueous solutions at room temperature. PAMAM G5-NH2 dendrimer combines about 70 molecules of the drug with equilibrium constant K ≅ 300, which is accompanied by an increase in the system order (ΔS < 0). Hydroxyl dendrimer, PAMAM G5-OH, combines about 14 molecules of 5-fluorouracil with equilibrium constant K ≅ 100. This process is accompanied by an increase in the system disorder (ΔS > 0).

Study of the interactions of PAMAM G3-NH2 and G3-OH dendrimers with 5‐fluorouracil in aqueous solutions

The results of spectroscopic measurements (increase in solubility, equilibrium dialysis, (1)H NMR titration) and calorimetric measurements (isothermal titration ITC) indicate spontaneous (ΔG<0) bonding of 5-fluorouracil by both cationic PAMAM G3-NH2 dendrimer and hydroxyl PAMAM G3-OH dendrimer in aqueous solutions. PAMAM G3-NH2 dendrimer bonds about n= 25±8 drug molecules. Some of them n1= 5±1 are bonded by terminal amine groups with equilibrium constant K1= 3890±930, while the remaining ones n2= 24 ±3 are bonded by amide groups with equilibrium constant K2= 110±30. Hydroxyl PAMAM G3-OH dendrimer bonds n=6.0±1.6 molecules of 5-fluorouracil through tertiary amine groups with equilibrium constant K= 65±10. The parameters of bonding 5-fluorouracil by PAMAM G3-NH2 and G3-OH dendrimer were compared with those of bonding this drug by the macromolecules of PAMAM of generations G4-NH2, G5-NH2 and G5-OH.

Spectroscopic and calorimetric studies on the interaction between PAMAM G4-OH and 5-fluorouracil in aqueous solutions.

The results of spectroscopic measurements (an increase in solubility, equilibrium dialysis, 1H NMR titration) and calorimetric measurements (isothermal titration ITC) indicate spontaneous (ΔG<0) binding of 5-fluorouracil molecules by PAMAM G4-OH dendrimer with terminal hydroxyl groups in an aqueous solution. PAMAM G4-OH dendrimer bonds about n=8±1 molecules of the drug with an equilibrium constant of K=70±10. The process of saturating the dendrimer active sites by the drug molecules is exothermal (ΔH<0) and is accompanied by an advantageous change in entropy (ΔS>0). The parameters of binding 5-fluorouracil by PAMAM G4-OH dendrimer were compared with those of binding this drug by the macromolecules of PAMAM G3-OH and G5-OH.

Formation of complexes between PAMAM-NH2 G4 dendrimer and l-α-tryptophan and l-α-tyrosine in water

Interactions between electromagnetic radiation and the side substituents of aromatic amino acids are widely used in the biochemical studies on proteins and their interactions with ligand molecules. That is why the aim of our study was to characterize the formation of complexes between PAMAM-NH2 G4 dendrimer and L-α-tryptophan and L-α-tyrosine in water. The number of L-α-tryptophan and L-α-tyrosine molecules attached to the macromolecule of PAMAM-NH2 G4 dendrimer and the formation constants of the supramolecular complexes formed have been determined. The macromolecule of PAMAM-NH2 G4 can reversibly attach about 25 L-α-tryptophan molecules with equilibrium constant K equal to 130±30 and 24±6 L-α-tyrosine molecules. This characterization was deduced on the basis of the solubility measurements of the amino acids in aqueous dendrimer solutions, the (1)H NMR and 2D-NOESY measurements of the dendrimer solutions with the amino acids, the equilibrium dialysis and the circular dichroism measurements of the dendrimer aqueous solutions with L-α-tryptophan. Our date confirmed the interactions of L-α-tryptophan and L-α-tyrosine with the dendrimer in aqueous solution and indicated a reversible character of the formed complexes.

Calorimetric and spectroscopic investigations of interactions between cucurbituril Q7 and gemcitabine in aqueous solutions

Studies on the interactions between cucurbituril Q7 and gemcitabine (Gem) hydrochloride in water were carried out using isothermal titration calorimetry (ITC) and electrospray ionization–mass spectrometry (ESI-MS). According to ITC and ESI-MS, the formation of this complex occurs in both the solution containing excess gemcitabine and the solution containing excess cucurbituril Q7. ITC results confirm the formation of a thermodynamically stable supramolecular complex with stoichiometry 1:1. The inclusion mechanism of Gem inside the cucurbituril macromolecule is spontaneous (

Interaction between PAMAM-NH2 G4 dendrimer and paracetamol in aqueous solution

\Delta G < 0