Papers by Barbara Dmochowska
Beilstein journal of organic chemistry, 2016
This paper presents a study on a series of quaternary ammonium salt (QAS) derivatives of glucopyr... more This paper presents a study on a series of quaternary ammonium salt (QAS) derivatives of glucopyranosides with an elongated hydrophobic hydrocarbon chain. The new N-[6-(β-D-glucopyranosyloxy)hexyl]ammonium bromides and their O-acetyl derivatives were analyzed via (1)H and (13)C NMR spectroscopy. The mutagenic activity of the newly synthesized QAS was investigated using two different techniques: The Vibrio harveyi luminescence assay and the Ames test. The obtained results support previous findings contesting QAS safety and indicate that QAS, specifically pyridinium derivatives, might be mutagenic.
NMR and MD Analysis of the Bonding Interaction of Vancomycin with Muramyl Pentapeptide
International Journal of Molecular Sciences, 2022
The article describes an NMR spectroscopy study of interactions between vancomycin and a muramyl ... more The article describes an NMR spectroscopy study of interactions between vancomycin and a muramyl pentapeptide in two complexes: vancomycin and a native muramyl pentapeptide ended with D-alanine (MPP-D-Ala), and vancomycin and a modified muramyl pentapeptide ended with D-serine (MPP-D-Ser). The measurements were made in a 9:1 mixture of H2O and D2O. The obtained results confirmed the presence of hydrogen bonds previously described in the literature. At the same time, thanks to the pentapeptide model used, we were able to prove the presence of two more hydrogen bonds formed by the side chain amino group of L-lysine and oxygen atoms from the vancomycin carboxyl and amide groups. This type of interaction has not been described before. The existence of these hydrogen bonds was confirmed by the 1H NMR and molecular modeling. The formation of these bonds incurs additional through-space interactions, visible in the NOESY spectrum, between the protons of the L-lysine amino group and a vancom...
Molecules, 2022
A series of quaternary diammonium salts derivatives of 1,4:3,6-dianhydro-l-iditol were synthesize... more A series of quaternary diammonium salts derivatives of 1,4:3,6-dianhydro-l-iditol were synthesized, using isommanide (1,4:3,6-dianhydro-d-mannitol) as a starting material. Both aromatic (pyridine, 4-(N,N-dimethylamino)pyridine (DMAP), (3-carboxamide)pyridine; N-methylimidazole) and aliphatic (trimethylamine, N,N-dimethylhexylamine, N,N-dimethyloctylamine, N,N-dimethyldecylamine) amines were used, giving eight gemini quaternary ammonium salts (QAS). All salts were tested for their antimicrobial activity against yeasts, Candida albicans and Candida glabrata, as well as bacterial Staphylococcus aureus and Escherichia coli reference strains. Moreover, antibacterial activity against 20 isolates of S. aureus collected from patients with skin and soft tissue infections (n = 8) and strains derived from subclinical bovine mastitis milk samples (n = 12) were evaluated. Two QAS with octyl and decyl residues exhibited antimicrobial activity, whereas those with two decyl residues proved to be th...
Molecules, 2022
Schiff bases are a vast group of compounds characterized by the presence of a double bond linking... more Schiff bases are a vast group of compounds characterized by the presence of a double bond linking carbon and nitrogen atoms, the versatility of which is generated in the many ways to combine a variety of alkyl or aryl substituents. Compounds of this type are both found in nature and synthesized in the laboratory. For years, Schiff bases have been greatly inspiring to many chemists and biochemists. In this article, we attempt to present a new take on this group of compounds, underlining of the importance of various types of Schiff bases. Among the different types of compounds that can be classified as Schiff bases, we chose hydrazides, dihydrazides, hydrazones and mixed derivatives such as hydrazide–hydrazones. For these compounds, we presented the elements of their structure that allow them to be classified as Schiff bases. While hydrazones are typical examples of Schiff bases, including hydrazides among them may be surprising for some. In their case, this is possible due to the ami...
TURKISH JOURNAL OF CHEMISTRY, 2019
Quaternary ammonium salts are a group of compounds with diverse biological properties, the most i... more Quaternary ammonium salts are a group of compounds with diverse biological properties, the most important of which are their antiviral, antibacterial, and antifungal activities. The quaternization reactions of 5'-O -tosyl derivatives of uridine and thymidine with triethylamine, trimethylamine, 4-( N , N -dimethylamino)pyridine, 2-methylpyridine, and pyridine are described in this article. Two of the synthesized compounds are exceptional because they are first of this type that demonstrate concentration-dependent antifungal in vitro activity against two species of the genus Candida in minimal YNB-SG medium. The experimental results have been extended by adding full atom molecular dynamics simulations and substrates and products energies evaluation.
Czwartorzędowe sole N-D-gliko- i alditolilopirydyniowe : synteza oraz właściwości
Przemysl Chemiczny, 2010
Wykaz stosowanych skrótów Wprowadzenie 1. Alditole jako składniki strukturalne aktywnych biologic... more Wykaz stosowanych skrótów Wprowadzenie 1. Alditole jako składniki strukturalne aktywnych biologicznie związków 2. Zastosowanie alditoli w syntezie polimerów 3. Metody syntezy alditoli oraz anhydroalditoli Uwagi końcowe Podziękowania Piśmiennictwo cytowane Dr Barbara Dmochowska w roku 1994 ukończyła studia chemiczne na Wydziale Chemii Uniwersytetu Gdańskiego w Gdańsku. Jest adiunktem w Pracowni Chemii Cukrów na Wydziale Chemii UG. Tematyka badawcza: tworzenie czwartorzędowych soli N-d-glikoamoniowych i alditoliloamoniowych z udziałem amin o potencjalnych właściwościach biologicznych.
Właściwości mutagenne czwartorzędowych soli aldtitolilo- i glikozylo-amoniowych
Przemysl Chemiczny, 2013
Wykaz stosowanych skrótów Wprowadzenie 1. Biosynteza antybiotyków urydynonukleozydowych 2. Wybran... more Wykaz stosowanych skrótów Wprowadzenie 1. Biosynteza antybiotyków urydynonukleozydowych 2. Wybrane antybiotyki nukleozydowe 2.1. Tunikamycyna 2.2. Mureidomycyna 2.3. Muramycyna 2.4. Kapuramycyna Uwagi końcowe Podziękowania Piśmiennictwo cytowane
Molecules, 2020
The synthesis of N-((methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl)ammonium salts ... more The synthesis of N-((methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl)ammonium salts are presented. To determine the effect of the nucleophile type and outgoing group on the quaternization reaction, selected aliphatic and heterocyclic aromatic amines reacted with: methyl 2,3-O-isopropylidene-5-O-tosyl-β-D-ribofuranoside or methyl 2,3-O-isopropylidene-5-O-mesyl-β-D-ribofuranoside or methyl 2,3-O-isopropylidene-5-O-triflyl-β-D-ribofuranoside were performed on a micro scale. High-resolution 1H- and 13C-NMR spectral data for all new compounds were recorded. Additionally, the single-crystal X-ray diffraction analysis for methyl 2,3-O-isopropylidene-5-O-mesyl-β-D-ribofuranoside and selected in silico interaction models are reported.
Journal of Molecular Structure, 2020
An unexpected side-reaction took place during the synthesis of quaternary ammonium salts with Otr... more An unexpected side-reaction took place during the synthesis of quaternary ammonium salts with Otriflyl derivatives of 1,4:3,6-dianhydrohexitols and tertiary alkylamines. The products were identified as tertiary amine derivatives of 1,4:3,6-dianhydrohexitol and tetraalkylammonium triflate. It was found that formation of the products was the consequence of the methyl group migration from QAS formed to the amine present in excess in the reaction mixture. Such reaction is a case of transquaternization, in which the exchange of the methyl group between two amines occurs.
Molecular dynamics study on the influence of C-terminal sugar substitution on dynamics and conformation of vancomycin derivatives
Journal of Carbohydrate Chemistry, 2017
ABSTRACT Computational investigations were performed to examine the effects of the addition of 2-... more ABSTRACT Computational investigations were performed to examine the effects of the addition of 2-acetamido-2-deoxy-β-D-galactopyranosylamine or 1-amino-1-deoxy-D-glucitol connected to the C-terminus of vancomycin with different linkers. The purpose of this modification was to find more effective vancomycin derivatives by providing alternative interactions between vancomycin moiety and the peptidoglycan precursor. Each prepared vancomycin–peptidoglycan complex was optimized and submitted to the molecular dynamics study and analysis. The analysis of overall root mean square deviation, changes in position and interactions involving modified part of vancomycin as well as cluster analysis were carried out. One of the proposed vancomycin analogues seems to be efficient vancomycin substitute. GRAPHICAL ABSTRACT
The synthesis and structure of gemini QASs of 1,4:3,6-dianhydro-l-iditol
Journal of Molecular Structure, 2015
Abstract New, efficient, straightforward method of synthesizing quaternary diammonium salts of 1,... more Abstract New, efficient, straightforward method of synthesizing quaternary diammonium salts of 1,4:3,6-dianhydro- l -iditol have been developed. This paper presents the synthesis and structural analysis of diammonium (gemini) salts, including their X-ray diffraction analysis, wherein the linking structure of nitrogen atoms consists of two fused furanoid rings. 1,4:3,6-dianhydro-2,5-di- O -triflyl- d -mannitol and four tertiary amines, i.e., 4-( N , N- dimethylamino)pyridine (DMAP), pyridine, trimethylamine and N , N- dimethyloctylamine, were used for the synthesis. All the syntheses were carried out under mild conditions by the direct nucleophilic displacement of the O -triflil group by the amine. Walden inversion of configuration at C2 and C5 atoms has occurred during the reaction, giving products with l - ido configuration. Furthermore, NMR and X-ray conformational analysis of 1,4:3,6-dianhydrohexitol residue was done. In most cases furanoid rings adopt the twisted conformation both in the crystal and in solution.
Journal of Molecular Graphics and Modelling, 2014
The formation of pyridinium salts in the transformation of three O-isopropylidene-protected mesyl... more The formation of pyridinium salts in the transformation of three O-isopropylidene-protected mesylates of furanoid sugar derivatives under pyridine action is considered at the B3LYP/6-31+G** computation level. All the structures were optimized in the gas phase, in chloroform and water. Activation barrier heights in the gas phase were also estimated at the B3LYP/6-311++G**, MPW1K/6-31+G** and MPW1K/6-311++G** levels. The conducted calculations, both in the gas phase (regardless of the computation level) and in solvents, revealed the barrier height increasing order as follows: 1 > 2 > 3 for the three reactions studied. The conformational behavior of the five-membered ring is discussed in the gas phase and in solvents. The fused dioxolane ring makes the furanoid ring less likely to undergo conformational changes. In the case of reaction 3, the furanoid ring shape does not change either in the gas phase or in solvents. All conformers are close to E 0 or 0 E.
Journal of Molecular Modeling, 2013
The energetics of the Menshutkin-like reaction between four mesylate derivatives and ammonia have... more The energetics of the Menshutkin-like reaction between four mesylate derivatives and ammonia have been computed using B3LYP functional with the 6-31+G** basis set. Additionally, MPW1K/6-31+G** level calculations were carried out to estimate activation barrier heights in the gas phase. Solvent effect corrections were computed using PCM/B3LYP/6-31+G** level. The conversion of the reactant complexes into ion pairs is accompanied by a strong energy decrease in the gas phase and in all solvents. The ion pairs are stabilized with two strong hydrogen bonds in the gas phase. The bifurcation at C2 causes a significant activation barrier increase. Also, bifurcation at C5 leads to noticeable barrier height differentiation. Both B3LYP/6-31+G** and MPW1K/6-31+G** activation barriers suggest the reaction 2 (2a+NH 3 ) to be the fastest in the gas phase. The reaction 4 is the slowest one in all environments.
Journal of Hazardous Materials, 2011
Quaternary ammonium salts are widely used in industrial, agricultural, healthcare and domestic ap... more Quaternary ammonium salts are widely used in industrial, agricultural, healthcare and domestic applications. They are believed to be safe compounds, with little or no health hazard to humans. However, in this report, we demonstrate that a series of newly synthesized quaternary ammonium salts containing carbohydrate moieties reveal potent mutagenic activities, as assessed by using the Vibrio harveyi bioluminescence mutagenicity test. d-Gluco-and d-galacto-derivatives were found to have a higher mutagenic potential than d-manno-derivatives. Among the former groups of compounds, the N-[2-(dglycopyranosyloxy)ethyl]-N,N,N-trimethylaminium salts were of the highest activity in the mutagenicity assay. These results suggest that the safety of quaternary ammonium salts may be lower than previously supposed, indicating a need for testing such compounds for their mutagenicity.
Cyclization ofN(Tetra-O-acetyl-d-gluco- andd-Mannopyranosyl)-Pyridinium Salts in a Methanolic Solution of Sodium Methylate
Journal of Carbohydrate Chemistry, 1998
N-(2,3,4,6-Tetra-O-acetyl-α-d-gluco-, β-d-gluco- and β-d-mannopyranosyl)-pyridinium salts were ob... more N-(2,3,4,6-Tetra-O-acetyl-α-d-gluco-, β-d-gluco- and β-d-mannopyranosyl)-pyridinium salts were obtained and their structures were determined by 2D H NMR spectroscopy. The compounds obtained were treated with a methanolic solution of sodium methylate. The β-anomer of the d-gluco derivative cyclizes via Brigl's anhydride but the α anomer is competitively transformed according to the SN2 and SN1 mechanisms. The β-d-manno derivative does not cyclize under
Investigative Opthalmology & Visual Science, 2003
Metabolomics, or metabolic profiling, is an emerging discipline geared to providing information o... more Metabolomics, or metabolic profiling, is an emerging discipline geared to providing information on a large number of metabolites, as a complement to genomics and proteomics. In the current study, a fluorine-labeled derivative of ascorbic acid (F-ASA), a major antioxidant-and UV-trapping molecule in the aqueous humor and the lens, was used to investigate the extent to which the lens accumulates potentially toxic degradation products of vitamin C. METHODS. Human lens epithelial cells (HLE-B3) and rat lenses were exposed to hyperglycemic or oxidative stress in vitro or in vivo and probed for accumulation of F-ASA, fluoro-dehydroascorbate (F-DHA), fluoro-2,3-diketogulonate (F-DKG), and their degradation products in protein-free extracts, by protondecoupled 750-MHz 19 F-nuclear magnetic resonance (NMR) spectroscopy. RESULTS. F-ASA and F-DHA were taken up into HLE B-3 cells by an Na ϩ -dependent transporter. Their uptake was unexpectedly only slightly affected by hyperglycemia in vitro, unless glutathione was severely depleted. Glycemic stress catalyzed oxidation of F-ASA into a single novel F-compound at Ϫ212.4 ppm, whereas F-DHA and F-DKG were the major degradation products observed after GSH depletion. In contrast, F-ASA uptake was markedly suppressed in diabetic cataractous rat lenses, which accumulated both the F-DHA and the Ϫ212.4-ppm compound. In an unexpected finding, the latter formed only from F-ASA and not F-DHA or F-DKG, suggesting a novel pathway of in vivo F-ASA degradation. Both the cells and the intact rat and human lenses were permeable to several advanced F-ASA and F-DHA degradation products, except F-DKG. The unknown compound at Ϫ212.4 ppm was the only F-ASA degradation product that spontaneously formed in rabbit aqueous humor upon incubation with F-ASA. CONCLUSIONS. These studies suggest the existence of a novel ascorbic-acid-degradation pathway in the lens and aqueous humor that is influenced by the nature of the oxidant stress. Under similar culture conditions, intact lenses are more prone to hyperglycemia-mediated oxidant stress than are lens epithelial cells, but both are permeable to various F-ASA degradation products, the structure and biological roles of which remain to be established. (Invest
International Congress Series, 2002
Ascorbic acid (ASA, Vitamin C) is a major antioxidant in vivo and precursor of Maillard reaction ... more Ascorbic acid (ASA, Vitamin C) is a major antioxidant in vivo and precursor of Maillard reaction intermediate compounds. Considerable evidence suggests impairment of ASA homeostasis in diabetic humans and animals is linked to the pathogenesis of diabetic complications . Yet, paradoxically, there is yet little information on how diabetes affects the homeostasis between ASA and its degradation products. Indeed ASA degradation products are similar to sugars, resulting in difficulty of following the catabolism of ASA in vivo. Furthermore, commercially available 14 C-ascorbic acid is labeled on carbon-1 atom that is lost into 14 CO 2 during ascorbic acid oxidation. We have developed a novel technique to study ASA catabolism in vivo based on 19 F-NMR spectroscopy that allows qualitative and quantitative analysis of most catabolites without chromatographic separation. The high sensitivity of this detection method allows us to quantitate micromolar tissue concentrations of ASA catabolites. For the purpose of the studies below, we have accomplished the synthesis of 6-deoxy-6-fluoroascorbic acid (F-ASA) which was changed C6-OH group of ASA to fluorine and found it was physicochemically almost equal to ASA . F-ASA was injected to normal (N) and STZ-diabetic rats (DB) and extracts from their blood, urine and tissue were analyzed with 750 MHz 19 F-NMR spectroscopy with proton decoupling. The data of plasma F-ASA and F-DHA levels after F-ASA injection (total F-ASA = 42.24 F 16.38 AM (N), 27.00 F 9.92 AM (DB)) suggested either accelerated cellular uptake of F-ASA in diabetic animals due to tissue depletion or accelerated oxidation and elimination in the urine. In urine, 12 to 15 yet unknown fluorodegradation products were observed, of which 6 were major compounds including fluorodiketogulonic acid (F-DKG) in addition to F-ASA and F-dehydroascorbic acid (F-DHA). F-ASA excretion ratio to total fluoro-degradation products in urine of DB was higher than that of N, indicating impairment of ASA anabolism in DB. The tissue data (in N and
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Papers by Barbara Dmochowska