Hydrophobic interaction in deuterium oxide

1975 ◽  
Vol 28 (4) ◽  
pp. 715 ◽  
Author(s):  
DG Oakenfull ◽  
DE Fenwick
Keyword(s):  
Free Energy ◽  
Hydrophobic Interaction ◽  
Deuterium Oxide ◽  
Hydrocarbon Chain ◽  
Micellar Solutions ◽  
Hydrocarbon Chain Length ◽  
Hydrocarbon Chains ◽  
Methylene Groups ◽  
Free Energy Of Binding ◽  
Kinetics Of

Methods previously used to study hydrophobic interaction in ordinary water have been used to measure the free energy of hydrophobic interaction between hydrocarbon chains in deuterium oxide at 25�: ��� (1) Conductance measurements on micellar solutions of a series of hexadecyltrimethylammonium carboxylates give the effect of hydrocarbon chain length on the free energy of binding a counter-ion (carboxylate ion) to the micelle, and hence the free energy of hydrophobic interaction. ��� (2) Comparison of the kinetics of the reaction between decylamine and 4-nitrophenyl decanoate with the kinetics of the corresponding reaction without hydrophobic side chains (the reaction between ethylamine and 4-nitrophenyl acetate) gives the extent to which hydrophobic interaction stabilizes the transition state. This then provides another estimate of the free energy of hydrophobic interaction. ��� The free energy of hydrophobic interaction in D2O was found to be - 1.76 kJ mol-1, for each contact between two methylene groups, compared with -1.40 kJ mol-1 in H2O. Hydrophobic interaction is therefore stronger in D2O than in H2O.

Conductometric study of hydrophobic interactions in aqueous solutions of double long-chain electrolytes

1973 ◽  
Vol 26 (12) ◽  
pp. 2649 ◽  
Author(s):  
DG Oakenfull ◽  
DE Fenwick
Keyword(s):  
Aqueous Solutions ◽  
Chain Length ◽  
Hydrophobic Interaction ◽  
Hydrophobic Interactions ◽  
Ion Pairs ◽  
Hydrocarbon Chain ◽  
Hydrocarbon Chain Length ◽  
Hydrocarbon Chains ◽  
Methylene Groups ◽  
Conductometric Study

We report measurements of the equivalent conductance (Λ) of aqueous solutions of a series of decyl- and hexadecyl-trimethylammonium carboxylates (acetate to undecanoate). In the decyl series, measurements were made on both sides of the critical micelle concentration (CMC). The CMC decreased when the hydrocarbon chain length of the carboxylate ion increased. In the hexadecyl series, measurements were confined to micellar solutions. ��� The results obtained below the CMC suggest that hydrophobic interaction between the hydrocarbon chains of decyltrimethylammonium undecanoate, decanoate, and nonanoate leads to the formation of ion- pairs. There was no evidence, however, for formation of ion-pairs by the shorter carboxylates. ��� By assuming that micellar ions obey the Onsager equation, we have derived a theoretical relationship between Λ and concentration above the CMC. An excellent fit of theoretical curve to experimental points can be obtained by adjusting the value of a single parameter. This parameter is {(m+1)/n}Kmic (where Kmic is the association constant for binding the carboxylate ion to the micelle and m/n is the ratio of tetra-alkylammonium ions to carboxylate ions in the micelle). ��� Plots of -RT ln[{(m+1)/n}Kmic] against the number of methylene groups on the carboxylate ion are linear for both series, which suggests that m/n is independent of the chain length of the carboxylate ion. Both lines have a slope equal to N�methy and Scheraga's estimate of the free energy of hydrophobic interaction between two methylene groups (-1.40 kJ/mol).

Kinetics of the reaction of the hydrophobic ester 4-nitrophenyl decanoate with long-chain N-alkylimidazoles above and below their critical micelle concentration

1974 ◽  
Vol 27 (10) ◽  
pp. 2149 ◽  
Author(s):  
DG Oakenfull ◽  
DE Fenwick
Keyword(s):  
Critical Micelle Concentration ◽  
Chain Length ◽  
Mole Fraction ◽  
Rate Constants ◽  
Hydrophobic Interactions ◽  
Hydrocarbon Chain ◽  
Hydrocarbon Chain Length ◽  
Hydrocarbon Chains ◽  
Kinetics Of ◽  
Long Chain

The kinetics of the reaction of 4-nitrophenyl decanoate with a series of straight-chain N-alkylimidazoles have been studied at 25� in water and aqueous ethanol. In water, below the critical micelle concentration of the N-alkylimidazole, hydrophobic interaction between the hydrocarbon chains of the reactants caused substantial increases in the reaction rate (up to about 200-fold) compared with the rate of reaction of 4-nitrophenyl acetate with N-methylimidazole. The rate constants, though, differed from those previously reported which were measured with a higher initial concentration of ester. No increase in rate with increasing hydrocarbon chain length could be detected in the presence of a large concentration of ethanol (mole fraction of 0.31) but a rate increase did occur in the presence of a more moderate concentration of ethanol (mole fraction of 0.10), confirming that hydrophobic interactions persist in this mixed solvent. The long-chain ester reacts rapidly with N-alkylimidazole micelles. Association constants (K) for binding the ester to the micelles and rate constants for the reaction of the bound ester (km) were estimated by following the conventional treatment of the kinetics of micelle-catalysed reactions. The value of K was found to increase sharply with increasing hydrocarbon chain length of the micelle but km showed the opposite trend.

Thermodynamics and mechanism of hydrophobic interaction

1977 ◽  
Vol 30 (4) ◽  
pp. 741 ◽  
Author(s):  
DG Oakenfull ◽  
DE Fenwick
Keyword(s):  
Free Energy ◽  
Volume Change ◽  
Hydrophobic Interaction ◽  
Ion Pairs ◽  
Hydrophobic Hydration ◽  
Partial Molar Volumes ◽  
Hydrocarbon Chain ◽  
Ion Pair ◽  
Pair Formation ◽  
Ion Pair Formation

.In the mixed solvent, 0.1 mole fraction ethanol-water, long-chain decyltrimethylammonium carboxylates form ion pairs. Ion-pair association constants (and hence the free energy of ion-pair formation) can be measured conductometrically. It is possible to separate the hydrophobic from the electrostatic contribution to the free energy of ion-pair formation by systematically varying the hydrocarbon chain length. We report measurements of the free energy of hydrophobic interaction (ΔG°HI) over the temperature range 278-328 K. The value of ΔG°HI becomes more negative (stronger hydrophobic interaction) with increasing temperature. The temperature coefficient of ΔG°HI was used to calculate the enthalpy (ΔH°HI) and entropy (ΔS°HI) of hydrophobic interaction. At low temperature the entropic contribution to the free energy is the larger but ΔH°HI, dominates at temperatures above c. 324 K. The volume change of hydrophobic interaction was similarly estimated from the volume change of ion-pair formation. We obtained values of apparent molar volume of the decyltrimethylammonium carboxylates (over a range of concentrations) from very precise density measurements. These could then be combined with the appropriate ion-pair association constant (from the conductance measurements) to give the partial molar volumes of the free ions and the ion pair. Hydrophobic interaction was found to be accompanied by a substantial increase in volume amounting to 10.2 ± 0.3 ml mol-1 for each pair of interacting methylene groups. Our results support the view that hydrophobic interaction occurs with a further ordering of water molecules over and above that which exists in the hydrophobic hydration layer surrounding an isolated hydrophobic molecule.

Development of Xanthine Based Inhibitors Targeting Phosphodiesterase 9A

2017 ◽  
Vol 14 (10) ◽  
pp. 1122-1137 ◽  
Author(s):  
Nivedita Singh ◽  
Parameswaran Saravanan ◽  
M.S. Thakur ◽  
Sanjukta Patra
Keyword(s):  
Free Energy ◽  
Active Site ◽  
Signal Transduction Pathway ◽  
Docking Study ◽  
Primary Objective ◽  
Cgmp Level ◽  
Active Site Residues ◽  
Aromatic Fragment ◽  
Docking Approach ◽  
Free Energy Of Binding

Background: Phosphodiesterases 9A (PDE9A) is one of the prominent regulating enzymes of the signal transduction pathway having highest catalytic affinity for second messenger, cGMP. When the cGMP level is lowered, an uncontrolled expression of PDE9A may lead to various neurodegenerative diseases. To regulate the catalytic activity of PDE9A, potent inhibitors are needed. Objective: The primary objective of the present study was to develop new xanthine based inhibitors targeting PDE9A. This study was an attempt to bring structural diversification in PDE9A inhibitor development because most of the existing inhibitors are constructed over pyrazolopyrimidinone scaffold. Methods: Manual designing and parallel molecular docking approach were used for the development of xanthine derivatives. In this study, N1, N3, N9 and C8 positions of xanthine scaffold were selected as substitution sites to design 200 new compounds. Reverse docking and pharmaceutical analyses were used for final validation of most promising compounds. Results: By keeping free energy of binding cut-off of -6.0 kcal/mol, 52 compounds were screened. The compounds with substitution at N1, N3 and C8 positions of xanthine showed good occupancy in PDE9A active site pocket with a significant interaction pattern. This was further validated by screening different factors such as free energy of binding, inhibition constant and interacting active site residues in the 5Å region. Substitution at C8 position with phenyl substituent determined the inhibition affinity of compounds towards PDE9A by establishing a strong hydrophobic - hydrophobic interaction. The alkyl chain at N1 position generated selectivity of compounds towards PDE9A. The aromatic fragment at N3 position increased the binding affinity of compounds. Thus, by comparative docking study, it was found that compound 39-42 formed selective interaction towards PDE9A over other members of the PDE superfamily. Conclusion: From the present study, N1, N3 and C8 positions of xanthine were concluded as the best sites for substitution for the generation of potent PDE9A inhibitors.

Synthesis and characterization of a series of 1-methyl-4-[2-aryl-1-diazenyl]piperazines and a series of ethyl 4-[2-aryl-1-diazenyl]-1-piperazinecarboxylates

2004 ◽  
Vol 82 (8) ◽  
pp. 1294-1303 ◽  
Author(s):  
Vanessa Renée Little ◽  
Keith Vaughan
Keyword(s):  
Free Energy ◽  
Chemical Shifts ◽  
Linear Free Energy Relationship ◽  
Piperazine Ring ◽  
Linear Free Energy ◽  
In Series ◽  
Methylene Groups ◽  
Diazonium Coupling ◽  
The Difference

1-Methylpiperazine was coupled with a series of diazonium salts to afford the 1-methyl-4-[2-aryl-1-diazenyl]piperazines (2), a new series of triazenes, which have been characterized by 1H and 13C NMR spectroscopy, IR spectroscopy, and elemental analysis. Assignment of the chemical shifts to specific protons and carbons in the piperazine ring was facilitated by comparison with the chemical shifts in the model compounds piperazine and 1-methylpiperazine and by a HETCOR experiment with the p-tolyl derivative (2i). A DEPT experiment with 1-methylpiperazine (6) was necessary to distinguish the methyl and methylene groups in 6, and a HETCOR spectrum of 6 enabled the correlation of proton and carbon chemical shifts. Line broadening of the signals from the ring methylene protons is attributed to restricted rotation around the N2-N3 bond of the triazene moiety in 2. The second series of triazenes, the ethyl 4-[2-phenyl-1-diazenyl]-1-piperazinecarboxylates (3), have been prepared by similar diazonium coupling to ethyl 1-piperazinecarboxylate and were similarly characterized. The chemical shifts of the piperazine ring protons are much closer together in series 3 than in series 2, resulting in distortion of the multiplets for these methylenes. It was noticed that the difference between these chemical shifts in 3 exhibited a linear free energy relationship with the Hammett substituent constants for the substituents in the aryl ring. Key words: triazene, piperazine, diazonium coupling, NMR, HETCOR, linear free energy relationship.

scholarly journals Structure and Interdigitation of Chain-Asymmetric Phosphatidylcholines and Milk Sphingomyelin in the Fluid Phase

Symmetry ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1441
Author(s):  
Moritz P. K. Frewein ◽  
Milka Doktorova ◽  
Frederick A. Heberle ◽  
Haden L. Scott ◽  
Enrico F. Semeraro ◽  
...  
Keyword(s):  
Chain Length ◽  
Hydration Shell ◽  
Fluid Phase ◽  
Hydrocarbon Chain ◽  
Specific Model ◽  
Glycerol Backbone ◽  
Membrane Composition ◽  
Membrane Structures ◽  
Hydrocarbon Chain Length ◽  
Dynamics Simulations

We addressed the frequent occurrence of mixed-chain lipids in biological membranes and their impact on membrane structure by studying several chain-asymmetric phosphatidylcholines and the highly asymmetric milk sphingomyelin. Specifically, we report trans-membrane structures of the corresponding fluid lamellar phases using small-angle X-ray and neutron scattering, which were jointly analyzed in terms of a membrane composition-specific model, including a headgroup hydration shell. Focusing on terminal methyl groups at the bilayer center, we found a linear relation between hydrocarbon chain length mismatch and the methyl-overlap for phosphatidylcholines, and a non-negligible impact of the glycerol backbone-tilting, letting the sn1-chain penetrate deeper into the opposing leaflet by half a CH2 group. That is, penetration-depth differences due to the ester-linked hydrocarbons at the glycerol backbone, previously reported for gel phase structures, also extend to the more relevant physiological fluid phase, but are significantly reduced. Moreover, milk sphingomyelin was found to follow the same linear relationship suggesting a similar tilt of the sphingosine backbone. Complementarily performed molecular dynamics simulations revealed that there is always a part of the lipid tails bending back, even if there is a high interdigitation with the opposing chains. The extent of this back-bending was similar to that in chain symmetric bilayers. For both cases of adaptation to chain length mismatch, chain-asymmetry has a large impact on hydrocarbon chain ordering, inducing disorder in the longer of the two hydrocarbons.

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