57 research outputs found
Statistical Inference for Ergodic Algorithmic Model (EAM), Applied to Hydrophobic Hydration Processes
Abstract: The thermodynamic properties of hydrophobic hydration processes can be represented in
probability space by a DualâStructure Partition Function {DSâPF} = {MâPF} â {TâPF}, which is the
product of a Motive Partition Function {MâPF} multiplied by a Thermal Partition Function {TâPF}.
By development of {DSâPF}, parabolic binding potential functions α) RlnKdual = (âÎG°dual/T)
={f(1/T)*g(T)} and ÎČ) RTlnKdual = (âÎG°dual) = {f(T)*g(lnT)} have been calculated. The resulting binding
functions are âconvolutedâ functions dependent on the reciprocal interactions between the primary
function f(1/T) or f(T) with the secondary function g(T) or g(lnT), respectively. The binding potential
functions carry the essential thermodynamic information elements of each system. The analysis of
the binding potential functions experimentally determined at different temperatures by means of
the Thermal Equivalent Dilution (TED) principle has made possible the evaluation, for each
compound, of the pseudoâstoichiometric coefficient Οw, from the curvature of the binding potential
functions. The positive value indicates convex binding functions (Class A), whereas the negative
value indicates concave binding function (Class B). All the information elements concern sets of
compounds that are very different from one set to another, in molecular dimension, in chemical
function, and in aggregation state. Notwithstanding the differences between, surprising equal
unitary values of niche (cavity) formation in Class A <hfor>A= â22.7 kJmolâ1 Οwâ1 sets with
standard deviation Ï= 3.1% and <sfor>A = â445JKâ1molâ1Οwâ1JKâ1molâ1Οwâ1 with standard
deviation Ï= 0.7%. Other surprising similarities have been found, demonstrating that all the data
analyzed belong to the same normal statistical population. The Ergodic Algorithmic Model (EAM)
has been applied to the analysis of important classes of reactions, such as thermal and chemical
denaturation, denaturation of proteins, iceberg formation or reduction, hydrophobic bonding, and
null thermal free energy. The statistical analysis of errors has shown that EAM has a general
validity, well beyond the limits of our experiments. Specifically, the properties of hydrophobic
hydration processes as biphasic systems generating convoluted binding potential functions, with
water as the implicit solvent, hold for all biochemical and biological solutions, on the ground that
they also are necessarily diluted solutions, statistically validated
Ergodic Algorithmic Model (EAM), with Water as Implicit Solvent, in Chemical, Biochemical, and Biological Processes
For many years, we have devoted our research to the study of the thermodynamic properties of hydrophobic hydration processes in water, and we have proposed the Ergodic Algorithmic
Model (EAM) for maintaining the thermodynamic properties of any hydrophobic hydration reaction
at a constant pressure from the experimental determination of an equilibrium constant (or other
potential functions) as a function of temperature. The model has been successfully validated by
the statistical analysis of the information elements provided by the EAM model for about fifty compounds. The binding functions are convoluted functions, RlnKeq = {f(1/T)* g(T)} and RTlnKeq =
{f(T)* g(lnT)}, where the primary linear functions f(1/T) and f(T) are modified and transformed into
parabolic curves by the secondary functions g(T) and g(lnT), respectively. Convoluted functions
are consistent with biphasic dual-structure partition function, {DS-PF} = {M-PF} · {T-PF} · {ζw},
composed by ({M-PF} (Density Entropy), {T-PF}) (Intensity Entropy), and {ζw} (implicit solvent). In
the present paper, after recalling the essential aspects of the model, we outline the importance of
considering the solvent as âimplicitâ in chemical and biochemical reactions. Moreover, we compare
the information obtained by computer simulations using the models till now proposed with âexplicitâ
solvent, showing the mess of information lost without considering the experimental approach of the
EAM model
Is the counterion responsible for the unusual thermodynamic behaviour of the aqueous solutions of gemini bispyridinium surfactants?
Metal-Chelating 2âHydroxyphenyl Amide Pharmacophore for Inhibition of Influenza Virus Endonuclease
The influenza virus PA endonuclease is an
attractive target for development of novel anti-influenza virus
therapeutics. Reported PA inhibitors chelate the divalent metal
ion(s) in the enzymeâs catalytic site, which is located in the Nterminal
part of PA (PA-Nter). In this work, a series of 2-
hydroxybenzamide-based compounds have been synthesized and biologically evaluated in order to identify the essential
pharmacophoric motif, which could be involved in functional sequestration of the metal ions (probably Mg2+) in the catalytic site
of PA. By using HL1, H2L2, and HL3 as model ligands with Mg2+ ions, we isolated and fully characterized a series of complexes
and tested them for inhibitory activity toward PA-Nter endonuclease. H2L2 and the corresponding Mg2+ complex showed an
interesting inhibition of the endonuclease activity. The crystal structures of the uncomplexed HL1 and H2L2 and of the isolated
magnesium complex [Mg(L3)2(MeOH)2]·2MeOH were solved by X-ray diffraction analysis. Furthermore, the speciation models
for HL1, H2L2, and HL3 with Mg2+ were obtained, and the formation constants of the complexes were measured. Preliminary
docking calculations were conducted to investigate the interactions of the title compounds with essential amino acids in the PANter
active site. These findings supported the âtwo-metalâ coordination of divalent ions by a donor triad atoms chemotype as a
powerful strategy to develop more potent PA endonuclease inhibitors
Nonviral gene-delivery by highly fluorinated gemini bispyridinium surfactant-based DNA nanoparticles
Biological and thermodynamic properties of a new homologous series of highly fluorinated bispyridinium
cationic gemini surfactants, differing in the length of the spacer bridging the pyridinium polar
heads in 1,10 position, are reported for the first time. Interestingly, gene delivery ability is closely
associated with the spacer length due to a structural change of the molecule in solution. This conformation
change is allowed when the spacer reaches the right length, and it is suggested by the trends
of the apparent and partial molar enthalpies vs molality. To assess the compoundsâ biological activity,
they were tested with an agarose gel electrophoresis mobility shift assay (EMSA), MTT proliferation
assay and Transient Transfection assays on a human rhabdomyosarcoma cell line. Data from atomic
force microscopy (AFM) allow for morphological characterization of DNA nanoparticles. Dilution
enthalpies, measured at 298 K, enabled the determination of apparent and partial molar enthalpies
vs molality. All tested compounds (except that with the longest spacer), at different levels, can deliver
the plasmid when co-formulated with 1,2-dioleyl-sn-glycero-3-phosphoethanolamine (DOPE). The
compound with a spacer formed by eight carbon atoms gives rise to a gene delivery ability that is
comparable to that of the commercial reagent. The compound with the longest spacer compacts
DNA in loosely condensed structures by forming bows, which are not suitable for transfection.
Regarding the compoundsâ hydrogenated counterparts, the tight relationship between the solutio
From ligand to complexes. Part 2. Remarks on human immunodeficiency virus type 1 integrase inhibition by β-diketo acid metal complexes
From ligand to complexes: Part 2: Remarks on human immunodeficiency virus type 1 integrase inhibition by beta-diketo acid metal complexes
In a previous work we reported results about the coordination ability of the diketo acid
pharmacophore, and discussed on the anti-HIV-1 IN activity of a series of synthesized ÎČ-diketo
acid metal complexes.
Herein, a further extension of this study is reported. In particular, a new set of complexes with
different stoichiometry was synthesized, and a series of potentiometric measurements were
conducted for two diketo acids as model ligands in the presence of other divalent metal ions in
order to outline a speciation model. The first X-ray solved structure of a diketo acid metal
complex is presented.
Moreover, we tested the obtained complexes for anti-HIV 1 IN activity. Furthermore, detailed
docking studies were conducted in order to investigate the mode of binding of the free ligands
compared with their metal complexes on the active site
On the mechanism of the cholesterol lowering ability of soluble dietary fibers: Interaction of some bile salts with pectin, alginate, and chitosan studied by isothermal titration calorimetry
Reducing high blood cholesterol is an important strategy to decrease the chances of a cardiovascular disease occurrence, the main cause of mortality in western developed countries. Therefore, the search for an alternative therapeutic or preventive approach being natural, biocompatible, and not toxic is still more relevant than ever. This need is particularly felt in Pediatrics for treating childhood hypercholesterolemia, due to statins interference in the production of steroid hormones in prepuberal children. Notwithstanding the general acceptance of the healthy role of the fibers in the diet, the mechanism underlying the cholesterol-lowering ability of soluble fibers is still under discussion. Therefore, we started a systematic study of the binding ability of some soluble dietary fibers (SDF) originated from different natural sources toward selected bile salts (BS) by isothermal titration calorimetry (ITC). Here we report the results of our ITC studies on the interaction of alginate, pectin and chitosan with sodium cholate (NaC), sodium deoxycholate (NaDC), sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC). Thermodynamic data on the micelle formation process of the above bile salts, as a premise to the study of their binding ability to the SDF, are also reported. Alginate does not show specific binding interaction with BS, while pectin shows a strong exothermic bond with NaDC in monomeric form. Chitosan, positively charged and soluble only at low pH, shows strong exothermic interactions with NaTC and NaTDC (soluble at pH = 3 in acetate buffer) with precipitate formation. For NaTC, the exothermic peak starts at about 5 mM. At this concentration NaTC bound on the fiber reaches locally the cmc value and micelles start forming on the fiber inducing its conformational change. For NaTDC the same process occurs at much lower concentrations, due to lower cmc, and with a greater quantity of heat involved. The first set of results here presented shows that for some SDF the binding of BS could be an important mechanism in cholesterol lowering but not the only one. The information here presented could be a starting point for the design of optimized functional foods with high cholesterol lowering ability
Ergodic Algorithmic Model (EAM), with Water as Implicit Solvent, in Chemical, Biochemical, and Biological Processes
For many years, we have devoted our research to the study of the thermodynamic properties of hydrophobic hydration processes in water, and we have proposed the Ergodic Algorithmic Model (EAM) for maintaining the thermodynamic properties of any hydrophobic hydration reaction at a constant pressure from the experimental determination of an equilibrium constant (or other potential functions) as a function of temperature. The model has been successfully validated by the statistical analysis of the information elements provided by the EAM model for about fifty compounds. The binding functions are convoluted functions, RlnKeq = {f(1/T)* g(T)} and RTlnKeq = {f(T)* g(lnT)}, where the primary linear functions f(1/T) and f(T) are modified and transformed into parabolic curves by the secondary functions g(T) and g(lnT), respectively. Convoluted functions are consistent with biphasic dual-structure partition function, {DS-PF} = {M-PF} ∙ {T-PF} ∙ {ζw}, composed by ({M-PF} (Density Entropy), {T-PF}) (Intensity Entropy), and {ζw} (implicit solvent). In the present paper, after recalling the essential aspects of the model, we outline the importance of considering the solvent as “implicit” in chemical and biochemical reactions. Moreover, we compare the information obtained by computer simulations using the models till now proposed with “explicit” solvent, showing the mess of information lost without considering the experimental approach of the EAM model
Solubility of Oxygen and inert substances in water
The solubility of oxygen in water at different temperatures has been analysed in the light of a statistical thermodynamic model.
According to the model, the oxygenâwater system is considered as a convoluted ensemble consisting of a reacting system, formed
by oxygen molecules and structured solvent with enthalpy difference DHf between discrete enthalpy levels, and of a non-reacting
system with continuous distribution of enthalpy levels. The enthalpy change of the reaction between oxygen and water, as
determined either by measuring the solubility of substances in water at different temperatures either by measuring heat
calorimetrically, is partially absorbed by some nw water molecules. The relaxed water molecules occupy part of the cavity formed
around solute. The part of heat absorbed, DHw depends linearly upon the temperature and causes the observed changes with
temperature of apparent enthalpy DHapp for the dissolution of oxygen and many other inert substances in water. The number nw
is proportional to the size of solute as shown by comparison with noble gases and other inert substances slightly soluble in water.
The solubilization process of all these substances is clearly analogous
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