Arkadiusz Kłys

Evaluation of poly(amidoamine) dendrimers as potential carriers of iminodiacetic derivatives using solubility studies and 2D-NOESY NMR spectroscopy

The interactions between dendrimers and different types of drugs are nowadays one of the most actively investigated areas of the pharmaceutical sciences. The interactions between dendrimers and drugs can be divided into: internal encapsulation, external electrostatic interaction, and covalent conjugation. In the present study, we investigated the potential of poly(amidoamine) (PAMAM) dendrimers for solubility of four iminodiacetic acid derivatives. We reported that PAMAM dendrimers contribute to significant solubility enhancement of iminodiacetic acid analogues. The nature of the dendrimer–drug complexes was investigated by 1H NMR and 2D-NOESY spectroscopy. The 1H NMR analysis proved that the water-soluble supramolecular structure of the complex was formed on the basis of ionic interactions between terminal amine groups of dendrimers and carboxyl groups of drug molecules, as well as internal encapsulation. The 2D-NOESY analysis revealed interactions between the primary amine groups of PAMAM dendrimers and the analogues of iminodiacetic acid. The results of solubility studies together with 1H NMR and 2D-NOESY experiments suggest that the interactions between PAMAM dendrimers of generation 1–4 and derivatives of iminodiacetic acid are based on electrostatic interactions and internal encapsulation.

Resolution and determination of the absolute configuration of 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxaldehyde

Abstract Racemic 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxaldehyde 1 was resolved via the formation of diastereomeric dioxolanes with ( S )-(+)-1-phenyl-1,2-ethanediol. Four stereoisomers were separated by column chromatography. The absolute configuration of one of them (2′′ R , 4′′ S, 1 R ) was established by X-ray diffraction. Acid hydrolysis of the dioxolanes afforded quantitatively ( R )- and ( S )-enantiomers of 1 . Optical rotatory dispersion (ORD) spectra of both enantiomers are also reported.

A Convenient Synthesis of Conjugated ω-Arylpolyenals via Wittig Reaction with (1,3-Dioxan-2-yl-methyl)triphenylphosphonium Bromide/Sodium Hydride

Abstract Commercially available reagent, (1,3-dioxan-2-yl-methyl)triphenylphosphonium bromide, sodium hydride and a catalytic amount of 18-crown-6 has proven efficient system for vinylic extension of ο-arylpolyenals.

Diastereomeric amides from rac-3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxylic acid and (S)-α-phenylethylamine: separation and determination of absolute configuration

Abstract Reaction of racemic 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxylic acid 1 with (S)-α-phenylethylamine in the presence of benzotriazol-1-yl-oxytris-(dimethylamino)phosphonium hexafluorophosphate and diisopropylethylamine leads to diastereomeric amides, (S,R)-2 and (S,S)-2. The diastereomers were separated by column chromatography and their absolute configurations were determined from NMR data supported by molecular modeling.

Planar chiral derivatives of 1,1′-diphosphaferrocene with potential application in nonlinear optics

Abstract Planar chiral “push–pull” derivatives of 1,1′-diphosphaferrocene were obtained in the Knoevenagel reaction starting from racemic or optically resolved 2-formyl-3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene. Their second-order non-linear optical (NLO) properties were studied by powder tests and the EFISHG technique at 1.907 μm.

The (η5-cyclopentadienyl)Fe(CO)2 complex of the (l)- and (d)-tryptophan methyl ester N-anion: synthesis and acylation of the amino function

Abstract The photochemical reaction of ( η 5 -C 5 H 5 )Fe(CO) 2 I with ( l )- and ( d )-tryptophan methyl ester in the presence of diisopropylamine in benzene leads to complexation of the ( η 5 -C 5 H 5 )Fe(CO) 2 moiety to the deprotonated indole nitrogen. This reaction takes place without detectable ( α . The amino group of the complex formed was acylated by treatment with p-chlorobenzoic acid and Fmoc-( l )-leucine in the presence of dicyclohexylcarbodiimide.

Unusual diastereoselective reduction of 2-propionyl-3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene to the corresponding alcohol by BH3·Me2S. X-Ray diffraction and DFT study

It has been found that BH3·Me2S reduces stereoselectively 2-propionyl-3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene 1 to the corresponding alcohol 2. The configuration (S,SP)/(R,RP) of 2 has been determined by X-ray diffraction study of the bis-W(CO)5 complex (3) of 2. The stereochemical outcome of this reaction has been explained assuming an exo-attack of borane at the s-trans conformation of 1. X-Ray diffraction study and DFT calculations confirmed greater thermodynamic stability of this conformation.

Carboxylation of 3,3', 4,4'-tetramethyl-1,1'-diphosphaferrocene with CO2 in the presence of AlCl3

Abstract 3,3′,4,4′-Tetramethyl-1,1′-diphosphaferrocene (1) is carboxylated by CO2 in the presence of AlCl3 at ambient pressure to afford 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene-2-carboxylic acid (2) in moderate (up to 30%) yield.

Synthesis and X-ray structure of bis-[Re2(CO)9] complex of 3,3', 4,4'-tetramethyl-1,1'-diphosphaferrocene functionalised complex as a potential radiopharmaceutical and metallocarbonyl marker

3,3′,4,4′-Tetramethyl-1,1′-diphosphaferrocene reacts with two mole equivalents of [Re 2 (CO) 10 ]/Me 3 NO to afford bis-[Re 2 (CO) 9 ] complex 4 . The X-ray structure of this complex revealed equatorial ReP bonds. The same reaction with a functionalised derivative of 3,3′4,4′-tetramethyl-1,1′-diphosphaferrocene 1b afforded N- succinimidyl ester 2 , potential reagent for introduction of the large amount of radioactive rhenium into target-specific biomolecules.

A validated 1H qNMR method for direct and simultaneous quantification of esculin, fraxin and (–)-epicatechin in Hippocastani cortex

A fast and precise qNMR method was developed for quantification of major bioactive constituents in the bark of horse chestnut and dry extracts prepared thereof. The method was optimised using 600 MHz spectrometer, and the final acquisition parameters (90°-pulse, acquisition time - 3.0 s, relaxation delay - 27 s, number of transients - 16) allowed for performing of quantitative experiments in under 15 min. The contents of three analytes were determined using specific 1H resonances at δ7.45 ppm for esculin, δ5.00 ppm for fraxin, and δ5.94 ppm for (-)-epicatechin. The validation showed good precision (RSD < 1.5%) and accuracy (95-103%), and adequate sensitivity (LODs in the range of 3.3-5.9 µg) of the measurements. The determined levels in commercial samples of Hippocastani cortex were in the range of 25.89-38.94 mg/g dry weight (dw) of the bark for esculin, 12.58-17.13 mg/g dw for fraxin and 10.42-13.96 mg/g dw for (-)-epicatechin, and in the dry extracts prepared thereof 97.02-143.51 mg/g, 45.78-58.92 mg/g and 28.07-46.29 mg/g, respectively. The obtained results were cross-validated by a HPLC-PDA method with the use of a fused-core column, and no statistical differences were found between the results obtained by both methodologies, but with the advantage of higher precision of the qNMR assay. The relevant variability in quantitative composition of the commercial samples emphasise the need to introduce quality control studies in production of preparations containing horse chestnut bark and the developed method was proved suitable for this purpose.