Further studies on the substrate specificity and inhibition of the stereospecific CS2 secondary alkylsulphohydrolase of Comamonas terrigena

A series of d-alkan-2-yl sulphate esters (C7–C14) were prepared by sulphation of the resolved parent alcohols by a method that entails complete retention of configuration. These sulphate esters were tested as substrates for the stereospecific CS2 secondary alkylsulphohydrolase of Comamonas terrigena. Vmax. reached a maximum with the C9 compound, whereas logKm decreased linearly as the alkyl-chain length was increased from C7 to C14. A parallel series of l-alkan-2-yl sulphates was also prepared, and these esters, together with homologous series of primary alkyl sulphates and primary alkanesulphonates, were shown to be competitive inhibitors of the CS2 enzyme. For each series of compounds, logKi values decreased linearly with increasing alkyl-chain length. Plots of chain length against the standard free energy of binding (ΔG0) of substrate and inhibitors to the CS2 enzyme showed that the standard free energy of association of a –CH2– group with the enzyme was 2.0–2.4kJ/mol for all classes of compound studied, indicating an important contribution from hydrophobic interactions to the overall binding. Plots for d-alkan-2-yl sulphate substrates and primary alkyl sulphate inhibitors were nearly coincident, suggesting that the overall interaction between a primary ester and the enzyme is the same as that between the isomeric secondary substrate and the enzyme. Plots for l-alkan-2-yl sulphate and alkanesulphonate inhibitors were very similar to each other, but were displaced by 1.5–3.0kJ/mol from that for substrate binding. This indicates that the binding of any one of these particular inhibitors involves one carbon atom fewer than the number involved in binding a substrate of the same chain length. These observations are discussed in terms of a three-point attachment of substrate to the enzyme involving the alkyl chain, sulphate group and the C-1 methyl group.

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Contribution of Molecular Structure to Self-Assembling and Biological Properties of Bifunctional Lipid-Like 4-(N-Alkylpyridinium)-1,4-Dihydropyridines

Pharmaceutics ◽

10.3390/pharmaceutics11030115 ◽

2019 ◽

Vol 11 (3) ◽

pp. 115 ◽

Cited By ~ 2

Author(s):

Martins Rucins ◽

Pavels Dimitrijevs ◽

Klavs Pajuste ◽

Oksana Petrichenko ◽

Ludmila Jackevica ◽

...

Keyword(s):

Chain Length ◽

Alkyl Chain ◽

Hydrophobic Interactions ◽

Biological Activities ◽

Biological Properties ◽

Alkyl Chain Length ◽

Critical Aggregation Concentration ◽

Self Assembling ◽

Basal Cytotoxicity

The design of nanoparticle delivery materials possessing biological activities is an attractive strategy for the development of various therapies. In this study, 11 cationic amphiphilic 4-(N-alkylpyridinium)-1,4-dihydropyridine (1,4-DHP) derivatives differing in alkyl chain length and propargyl moiety/ties number and position were selected for the study of their self-assembling properties, evaluation of their cytotoxicity in vitro and toxicity on microorganisms, and the characterisation of their interaction with phospholipids. These lipid-like 1,4-DHPs have been earlier proposed as promising nanocarriers for DNA delivery. We have revealed that the mean diameter of freshly prepared nanoparticles varied from 58 to 513 nm, depending upon the 4-(N-alkylpyridinium)-1,4-DHP structure. Additionally, we have confirmed that only nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3 and 6, and by 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 were stable after two weeks of storage. The nanoparticles of these compounds were found to be homogenous in size distribution, ranging from 124 to 221 nm. The polydispersity index (PDI) values of 1,4-DHPs samples 3, 6, 10, and 11 were in the range of 0.10 to 0.37. We also demonstrated that the nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3, 6, and 9, and 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 had zeta-potentials from +26.07 mV (compound 6) to +62.80 mV (compound 11), indicating a strongly positive surface charge and confirming the relative electrostatic stability of these nanoparticle solutions. Transmission electron microscopy (TEM) images of nanoaggregates formed by 1,4-DHPs 3 and 11 confirmed liposome-like structures with diameters around 70 to 170 nm. The critical aggregation concentration (CAC) value interval for 4-(N-alkylpyridinium)-1,4-DHP was from 7.6 µM (compound 11) to 43.3 µM (compound 6). The tested 4-(N-alkylpyridinium)-1,4-DHP derivatives were able to quench the fluorescence of the binary 1,6-diphenyl-1,3,5-hexatriene (DPH)—1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) system, demonstrating hydrophobic interactions of 1,4-DHPs with phospholipids. Thus, 4-(N-dodecylpyridinium)-1,4-DHP derivative 3 quenched the fluorescence of the DPH–DPPC system more efficiently than the other 4-(N-alkylpyridinium)-1,4-DHP derivatives. Likewise the compound 3, also 4-(N-dodecylpyridinium)-1,4-DHP derivative 9 interacted with the phospholipids. Moreover, we have established that increasing the length of the alkyl chain at the quaternised nitrogen of the 4-(N-alkylpyridinium)-1,4-DHP molecule or the introduction of propargyl moieties in the 1,4-DHP molecule significantly influences the cytotoxicity on HT-1080 (human fibrosarcoma) and MH-22A (mouse hepatocarcinoma) cell lines, as well as the estimated basal cytotoxicity. Additionally, it was demonstrated that the toxicity of the 4-(N-alkylpyridinium)-1,4-DHP derivatives on the Gram-positive and Gram-negative bacteria species and eukaryotic microorganism depended on the presence of the alkyl chain length at the N-alkyl pyridinium moiety, as well as the number of propargyl groups. These lipid-like compounds may be proposed for the further development of drug formulations to be used in cancer treatment.

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Purification and properties of the P2 primary alkylsulphohydrolase of the detergent-degrading bacterium pseudomonas C12B

Biochemical Journal ◽

10.1042/bj1850023 ◽

1980 ◽

Vol 185 (1) ◽

pp. 23-31 ◽

Cited By ~ 15

Author(s):

J M Cloves ◽

K S Dodgson ◽

G F White ◽

J W Fitzgerald

Keyword(s):

Free Energy ◽

Chain Length ◽

Alkyl Chain ◽

Competitive Inhibition ◽

Deae Cellulose ◽

Intact Protein ◽

Alkyl Sulphate ◽

Degrading Bacterium ◽

Purification And Properties ◽

Considerable Length

The P2 primary alkylsulphohydrolase of the soil bacterium Pseudomonas C12B was purified to homogeneity (200-250-fold) by column chromatography on DEAE-cellulose, Sephadex G-100 and butyl-agarose. The intact protein is a dimer with a mol. wt. of 160 000. Activity towards primary alkyl sulphate esters was maximal at pH 8.3, varied little in the range pH 7.8-8.7, but decreased sharply at higher pH. For a homologous series of primary alkyl sulphate substrates (C6-C12), logKm decreased linearly with increasing chain length, corresponding to a contribution to the free energy of association between enzyme and substrate of ‒2.5kJ/mol for each additional CH2 group in the alkyl chain. logKi for the competitive inhibition by secondary alkyl 2-sulphate esters followed a similar pattern (-2.4kJ/mol for each additional CH2 group) except that only n-1 carbon atoms effectively participate in hydrophobic bonding, implying that the C-1 methyl group is not involved. logKi values for inhibition primary alkanesulphonates also depended linearly on chain length but with a diminished gradient, indicating a free-energy increment of ‒1.2kJ/mol per additional CH2 group. The collective results showed the presence of a hydrophobic site on the enzyme capable of accomodating an alkyl chain of considerable length. Cationic structures (in the form of arginine, lysine or histidine), whose presence might be expected for binding the anionic sulphate group, were not detectable at the active site.

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Purification and properties of the S1 secondary alkylsulphohydrolase of the detergent-degrading micro-organism, Pseudomonas C12B

Biochemical Journal ◽

10.1042/bj1690659 ◽

1978 ◽

Vol 169 (3) ◽

pp. 659-667 ◽

Cited By ~ 14

Author(s):

Barbara Bartholomew ◽

Kenneth S. Dodgson ◽

Stephen D. Gorham

Keyword(s):

Chain Length ◽

Alkyl Chain ◽

Competitive Inhibitor ◽

Sulphate Group ◽

Experimental Conditions ◽

Alkyl Sulphate ◽

Purification And Properties ◽

Crude Preparation ◽

A Chain ◽

Comamonas Terrigena

The S1 secondary alkylsulphohydrolase of the detergent-degrading micro-organism, Pseudomonas C12B, was separated from other alkylsulphohydrolases and purified to homogeneity. Under the experimental conditions used the enzyme completely hydrolysed d-octan-2-yl sulphate (d-1-methylheptyl sulphate), but showed no activity towards the corresponding l-isomer. Additional evidence has been obtained to indicate that it is probably optically stereospecific for d-secondary alkyl sulphate esters with the ester sulphate group at C-2 and with a chain length of at least seven carbon atoms. Enzyme activity towards racemic samples of heptan-2-yl sulphate (1-methylhexyl sulphate), octan-2-yl sulphate and decan-2-yl sulphate (1-methylnonyl sulphate) increased with increasing chain length. l-Octan-2-yl sulphate is a competitive inhibitor of the enzyme, as are certain primary alkyl sulphates and primary alkanesulphonates. Inhibition by each of the last two types of compounds is characteristic of the behaviour of an homologous series. Inhibition increases with increasing chain length and plots of log Ki values against the number of carbon atoms in each alkyl chain show the expected linear relationship. A crude preparation of the S2 secondary alkylsulphohydrolase was used to show that this particular enzyme hydrolyses l-octan-2-yl sulphate, but is probably inactive towards the corresponding d-isomer. The similarity of the S1 and S2 enzymes to the CS2 and CS1 enzymes respectively of Comamonas terrigena was established, and some comments have been made on the possible roles of these and other alkylsulphohydrolases in the biodegradation of detergents.

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Influence of alkyl chain length on the action of acetylated monoglycerides as plasticizers for poly (vinyl chloride) food packaging film

Food Packaging and Shelf Life ◽

10.1016/j.fpsl.2020.100619 ◽

2021 ◽

Vol 27 ◽

pp. 100619

Author(s):

Chang Woo Kwon ◽

Pahn-Shick Chang

Keyword(s):

Chain Length ◽

Vinyl Chloride ◽

Food Packaging ◽

Alkyl Chain ◽

Alkyl Chain Length ◽

Packaging Film ◽

Poly Vinyl Chloride

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Silver Nanoparticles Stabilized with Phosphorus-Containing Heterocyclic Surfactants: Synthesis, Physico-Chemical Properties, and Biological Activity Determination

Nanomaterials ◽

10.3390/nano11081883 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1883

Author(s):

Martin Pisárčik ◽

Miloš Lukáč ◽

Josef Jampílek ◽

František Bilka ◽

Andrea Bilková ◽

...

Keyword(s):

Silver Nanoparticles ◽

Biological Activity ◽

Zeta Potential ◽

Chain Length ◽

Alkyl Chain ◽

Chemical Properties ◽

Alkyl Chain Length ◽

Microbial Pathogens ◽

Physico Chemical ◽

Phosphorus Containing

Phosphorus-containing heterocyclic cationic surfactants alkyldimethylphenylphospholium bromides with the alkyl chain length 14 to 18 carbon atoms were used for the stabilization of silver nanodispersions. Zeta potential of silver nanodispersions ranges from +35 to +70 mV, which indicates the formation of stable silver nanoparticles (AgNPs). Long-chain heptadecyl and octadecyl homologs of the surfactants series provided the most intensive stabilizing effect to AgNPs, resulting in high positive zeta potential values and smaller diameter of AgNPs in the range 50–60 nm. A comparison with non-heterocyclic alkyltrimethylphosphonium surfactants of the same alkyl chain length showed better stability and more positive zeta potential values for silver nanodispersions stabilized with heterocyclic phospholium surfactants. Investigations of biological activity of phospholium-capped AgNPs are represented by the studies of antimicrobial activity and cytotoxicity. While cytotoxicity results revealed an increased level of HepG2 cell growth inhibition as compared with the cytotoxicity level of silver-free surfactant solutions, no enhanced antimicrobial action of phospholium-capped AgNPs against microbial pathogens was observed. The comparison of cytotoxicity of AgNPs stabilized with various non-heterocyclic ammonium and phosphonium surfactants shows that AgNPs capped with heterocyclic alkyldimethylphenylphospholium and non-heterocyclic triphenyl-substituted phosphonium surfactants have the highest cytotoxicity among silver nanodispersions stabilized by the series of ammonium and phosphonium surfactants.

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