Structural thermodynamics of lamellar cationic lipid-DNA complex: DNA compressibility modulus

We have studied theoretically the compressibility modulus B of DNA and complexation adsorption isotherms of DNA and lipids, as a function of DNA spacing d(DNA) and NaCl electrolyte concentration, respectively, in isoelectric states of lamellar DNA/cationic lipid (CL) self-assemblies. The electrostatic free energy derived from the Poisson-Boltzmann theory predicts partial agreement with measured B values for interhelical separations d(DNA)>33 A when use is made of a fit of hydration repulsion from bulk DNA hexagonal phases in solution. For lower interchain separations the prediction worsens due to the hydration interaction that overcomes the electrostatic contribution. An exact match of the system's counterion electrochemical potentials and the coions of salt in aqueous phase leads to the electrostatic part of the free energy that renders isotherms of d(DNA) versus ionic strength in qualitative consistency with general trends of available experimental data of CL-DNA complexes.     

Phase evolution of lamellar cationic lipid-DNA complex: steric effect of an electrolyte

The complexation isotherms of DNA plus lipids of a symmetric lamellar cationic lipid-DNA system were determined within a mean field free energy. The free energy incorporates the ion's finite size of NaCl simple electrolyte in solution and makes use of known structure data on this complex. The results for the predicted isotherms are in qualitative agreement with the trends of the experimental data for this property.     

Temperature-dependence of cationic lipid bilayer intermixing: possible role of interdigitation

In this work, we investigated the properties of a fusogenic cationic lipid, diC14-amidine, and show that this lipid possesses per se the capacity to adopt either an interdigitated structure (below and around its transition temperature) or a lamellar structure (above the transition temperature). To provide experimental evidence of this lipid bilayer organization, phospholipids spin-labeled at different positions of the hydrocarbon chain were incorporated into the membrane and their electron spin resonance (ESR) spectra were recorded at different temperatures. For comparison, similar experiments were performed with dimyristoyl phosphatidylcholine, a zwitterionic lipid (DMPC) which adopts a bilayer organization over a broad temperature range. Lipid mixing between diC14-amidine and asolectin liposomes was more efficient below (10-15 °C) than above the transition temperature (above 25 °C). This temperature-dependent "fusogenic" activity of diC14-amidine liposomes is opposite to what has been observed so far for peptides or virus-induced fusion. Altogether, our data suggest that interdigitation is a highly fusogenic state and that interdigitation-mediated fusion occurs via an unusual temperature-dependent mechanism that remains to be deciphered.     

Two-dimensional lipid mixing entropy regulates the formation of multicomponent lipoplexes

The mechanism of formation of multicomponent lipoplexes was investigated by means of synchrotron Small-Angle X-ray Diffraction (SAXD). Mixed lipid dispersions were prepared by mixing different populations of binary cationic liposomes. When adding DNA to mixed lipid dispersions, multicomponent lipoplexes spontaneously formed exhibiting structural properties, i.e., membrane thickness, surface charge density, and one-dimensional DNA packing density, intermediate between those of binary lipoplexes. These results suggested that DNA lets liposomes come into contact and fuse and that a complete lipid mixing at the molecular level occurs. The equilibrium structure of multicomponent lipoplexes was found to be unique and did not depend on the number and kind of populations composing lipid dispersion but only on the lipid species involved and on their relative molar ratio. According to recent theoretical models we identified two-dimensional lipid mixing entropy as the key factor regulating the existence of only multicomponent lipoplexes with ideally mixed lipid species.     

Effect of mixing on the formation of complexes of hyperbranched cationic polyelectrolytes and anionic surfactants

The effect of different mixing protocols on the charged nature and size distribution of the aqueous complexes of hyperbranched poly(ethylene imine) (PEI) and sodium dodecyl sulfate (SDS) was investigated by electrophoretic mobility and dynamic light scattering measurements at different pH values, polyelectrolyte concentrations, and ionic strengths. It was found that at large excess of the surfactant a colloidal dispersion of individual PEI/SDS nanoparticles forms via an extremely rapid mixing of the components by means of a stop-flow apparatus. However, the application of a less efficient mixing method under the same experimental conditions might result in large clusters of the individual PEI/SDS particles as well as in a more extended precipitation regime compared with the results of stop-flow mixing protocol. The study revealed that the larger the charge density and concentration of the PEI, the more pronounced the effect of mixing becomes. It can be concluded that an efficient way to avoid precipitation in the solutions of oppositely charged polyelectrolytes and surfactants might be provided by extending the range of kinetically stable colloidal dispersion of polyelectrolyte/surfactant nanoparticles via the application of appropriate mixing protocols.     

DNA strand exchange stimulated by spontaneous complex formation with cationic comb-type copolymer

Cationic comb-type copolymers (CCCs) composed of a polycation backbone and water-soluble side chains accelerate by 4-5 orders the DNA strand exchange reaction (SER) between double helical DNA and its homologous single-strand DNA. The accelerating effect is considered due to alleviation of counterion association during transitional intermediate formation in sequential displacement pathway. CCCs stabilize not only matured hybrids but also the nucleation complex to accelerate hybridization.     

The crystalline molecular complex between cationic surfactant and some additive substances: Part I: complex formation with phenol derivative as additives

It was established that many crystalline molecular complexes composed of cationic surfactants such as CTAB and several phenolic derivatives were obtained from an appropriate concentrated solution system in which a remarkable viscoelasticity was developed. It is revealed that the molecular complexes have an unambiguous composition of 1:1 molar ratio of surfactants to phenolic additives. The molecular complexes also showed characteristic endothermicity of a degree that suggests the specimens to be single and a pure species. However, through repeated runs the thermal stability of the complexes seemed to be rather poor, as exhibited by a profile change in thermograms of DSC.     

The role of complex formation in partition paper chromatography

Further information of the possible effects of chemical reaction on differential ionic movement in partition paper chromatography was obtained by developing chromatograms of fifteen inorganic cations with alcoholic solvents containing varying concentrations of disodium ethylenediaminetetraacetate.An examination of these chromatograms indicated that variations in the concentrations of E.D.T.A. in the solvent or the presence of free acid or ammonia resulted in marked changes in R_F values and spot areas.It is therefore suggested that care should be taken in interpreting the results of any chromatograms developed with solvents capable of chemical interaction with the “spotted” solute.     

Study of inclusion complex formation between a cationic surfactant, two cyclodextrins and a drug

In this study inclusion of hexadecyltrimethylammonium bromide (HTAB) with α-, and β-cyclodextrin (CD) in the presence and the absence of bromhexine (BH) was investigated using ion-selective electrode method. The association constants of HTAB with CDs were determined by potentiometry and were close to literature values. The obtained results indicated that α-CD formed 1:1 and 1:2 inclusion complexes, but β-CD formed only a 1:1 inclusion complex. In the presence of drug, the interaction between CDs and HTAB decreased, because both drug and HTAB could interact with CDs. The results showed that the interaction between drug and CDs are greater than HTAB and CDs. The stoichiometry of the inclusion complexes, the critical aggregation concentration (CAC), the monomer surfactant concentration of HTAB, [HTAB]_f, and also the effect of the inclusion complex on the micellization process of the HTAB were determined by conductivity measurements.     

Charge relocation in cationic diene complexes: formation of an iminium-substituted allyl complex and its deprotonation to an enamine

The reaction of [Mo(NCME)₂(CO)₂(η⁵-C₉H₇)][BF₄] (1) with 1-dimethylaminocyclohexa-1,3-diene affords the cationic η³-allyl complex [Mo(η³-C₆H₇NMe₂)(CO)₂- (η⁵-C₉H₇)][BF₄] (3), in which the positive charge is located at an exocyclic iminium centre. Addition of Li[N(SiMe₃)₂] to 3 results in deprotonation and the formation of an enamine species [Mo(η³-C₆H₆NMe₂)(CO)₂(η⁵-C₉H₇)] (8), which undergoes stereofacial attack upon treatment with electrophiles.     

A two-state model for the multilamellar structure of a DNA/cationic lipid complex in the bulk

Polyanionic DNA can bind electrostatically with cationic lipids to form a complex used for gene delivery and nanostructure construction. Here, we reveal two multilamellar phases, L(I) and L(II), characterized by distinct states of lipid packing and DNA conformation in a DNA/cationic lipid complex in the bulk state. The L(II) phase, formed when the lipids are in excess of DNA in terms of overall ionic charge, is composed of B-DNA confined between the bilayers with the lipid tails aligning normal to the lamellar interface. When DNA becomes in excess of the lipids, the L(I) phase in which the DNA is bound with the tilted lipid chains adopting the A conformation is favored because this configuration offers more economical electrostatic binding between these two components.     

Light-scattering study of polyelectrolyte complex formation between anionic and cationic nanogels in an aqueous salt-free system

We studied complex formation in an aqueous salt-free system (pH approximately 3 and at 25 degrees C) between nanogel particles having opposite charges. Anionic gel (AG) and cationic gel (CG) particles consist of lightly cross-linked N-isopropylacrylamide (NIPA) copolymers with 2-acrylamido-2-methylpropane sulfonic acid and with 1-vinylimidazole, respectively. The number of charges per particle was -4490 for AG and +20 300 for CG, as estimated from their molar masses (3.33 MD for AG and 11.7 MD for CG) by static light scattering (SLS) and their charge densities (1.35 mmol/g for AG and 1.74 mmol/g for CG) by potentiometric titration. The complexes were formed through the addition of AG to CG and vice versa using a turbidimetric titration technique. At the endpoint of the titration, the aggregate formed was a complex based upon stoichiometric charge neutralization: CG(n)()(+) + xAG(m)()(-) --> CG(n)()(+) (AG(m)()(-))(x)() where x = (n)()/(m)(). At different stages of the titration before the endpoint, the resulting complexes were examined in detail using dynamic light scattering, SLS, and electrophoretic light scattering (ELS). The main results are summarized as follows: (i) When AG with a hydrodynamic radius (R(h)) of 119 nm is added to CG (R(h) approximately 156 nm), the (R(h)) of the complex size decreases from 156 to 80 nm. (ii) In contrast to this (R(h)) change, the molar mass increases from 11.7 MD to 24 MD with increasing amounts of added AG. (iii) Upon addition of CG to AG, the complex formed has the same size ((R(h)) approximately 80 nm) and the same molar mass (55 +/- 2.5 MD) until 55 +/- 5% of AG has been consumed in the complexation. To understand these results, we used the following two models: the random model (RM), in which the added AG particles uniformly bind to all of the CG particles in the system via a strong electrostatic attraction, and the all-or-none model (AONM), in which part of the AG particles in the system preferably bind to the added CG particles to neutralize their electric charges but the other AG particles are uncomplexed and remain in the system. The complex formations upon addition of AG to CG and CG to AG were elucidated in terms of RM and AONM, respectively.     

Unusual alkyl group activation and cationic complex formation from a novel lutetium dialkyl complex supported by a tridentate monoanionic ligand

We report herein the synthesis and characterization of a lutetium dialkyl complex supported by a multidentate, anilido-pyridine-imine ligand and its subsequent transformation into an unprecedented cationic monoalkyl derivative.     

Migration of a cationic polymer between lipid vesicles

The adsorption of a synthetic polycation, poly(N-ethyl-4-vinylpyridinium bromide) (PEVP), on the surface of bilayer lipid vesicles (liposomes) and the migration of adsorbed macromolecules between the liposomes are studied. Liposomes of three types are used, including (1) traditional two-component liposomes composed of neutral phosphatidylcholine (PC) and anionic cardiolipin (CL); (2) three-component liposomes consisting of PC, CL, and cationic dicetyldimethylammonium bromide (DCMAB); and (3) anionic PC/CL liposomes with a nonionic surfactant, poly(ethylene oxide)-cetyl alcohol ether (Briij 58), incorporated into their bilayers. The adsorption of PEVP on the surface of PC/CL liposomes is accompanied by their aggregation. Using the fluorescence method, it is shown that the units (segments) of the polycation undergo partial redistribution between the liposomes inside the aggregates formed from PC/CL liposomes (with and without a fluorescent label) and PEVP. On the contrary, three-component PC/CL/DCMAB and PC/CL/Briij liposomes are not aggregated, even with the complete neutralization of their charges by adsorbed PEVP. In both cases, the migration of PEVP molecules between individual (nonaggregated) liposomes is observed. Possible reasons for the aggregative stability of the three-component PC/CL/DCMAB and PC/CL/Briij liposomes and the mechanism of interliposome migration of PEVP in such systems are discussed.     

Phosphate-mediated arginine insertion into lipid membranes and pore formation by a cationic membrane peptide from solid-state NMR

The insertion of charged amino acid residues into the hydrophobic part of lipid bilayers is energetically unfavorable yet found in many cationic membrane peptides and protein domains. To understand the mechanism of this translocation, we measured the (13)C-(31)P distances for an Arg-rich beta-hairpin antimicrobial peptide, PG-1, in the lipid membrane using solid-state NMR. Four residues, including two Arg's, scattered through the peptide were chosen for the distance measurements. Surprisingly, all residues show short distances to the lipid (31)P: 4.0-6.5 A in anionic POPE/POPG membranes and 6.5-8.0 A in zwitterionic POPC membranes. The shortest distance of 4.0 A, found for a guanidinium Czeta at the beta-turn, suggests N-H...O-P hydrogen bond formation. Torsion angle measurements of the two Arg's quantitatively confirm that the peptide adopts a beta-hairpin conformation in the lipid bilayer, and gel-phase 1H spin diffusion from water to the peptide indicates that PG-1 remains transmembrane in the gel phase of the membrane. For this transmembrane beta-hairpin peptide to have short (13)C-(31)P distances for multiple residues in the molecule, some phosphate groups must be embedded in the hydrophobic part of the membrane, with the local (31)P plane parallel to the beta-strand. This provides direct evidence for toroidal pores, where some lipid molecules change their orientation to merge the two monolayers. We propose that the driving force for this toroidal pore formation is guanidinium-phosphate complexation, where the cationic Arg residues drag the anionic phosphate groups along as they insert into the hydrophobic part of the membrane. This phosphate-mediated translocation of guanidinium ions may underlie the activity of other Arg-rich antimocrobial peptides and may be common among cationic membrane proteins.     

Electrostatics of DNA complexes with cationic lipid membranes

We present the exact solutions of the linear Poisson-Boltzmann equation for several problems relevant to electrostatics of DNA complexes with cationic lipids. We calculate the electrostatic potential and electrostatic energy for lamellar and inverted hexagonal phases, concentrating on the effects of dielectric boundaries. We compare our results for the complex energy with the known results of numerical solution of the nonlinear Poisson-Boltzmann equation. Using the solution for the lamellar phase, we calculate the compressibility modulus and compare our findings with the experimental data available. Also, we treat charge-charge interactions across, along, and between two low-dielectric membranes. We obtain an estimate for the strength of electrostatic interactions of one-dimensional DNA smectic layers across the lipid membrane. We discuss in the end some aspects of two-dimensional DNA condensation and DNA-DNA attraction in the DNA-lipid lamellar phase in the presence of di- and trivalent cations. We analyze the equilibrium DNA-DNA separations in lamellar complexes using the recently developed theory of electrostatic interactions of DNA helical charge motifs.     

Studies of mixed micelle formation between cationic gemini and cationic conventional surfactants

Mixed micellization of dimeric cationic surfactants tetramethylene-1,4-bis(hexadecyldimethylammonium bromide)(16-4-16), hexamethylene-1,6-bis(hexadecyldimethylammonium bromide) (16-6-16) with monomeric cationic surfactants hexadecyltrimethylammonium bromide (CTAB), cetylpyridinium bromide (CPB), cetylpyridinium chloride (CPC), and tetradecyltrimethylammonium bromide (TTAB) have been studied by conductivity and steady-state fluorescence quenching techniques. The behavior of mixed systems, their compositions, and activities of the components have been analyzed in the light of Rubingh's regular solution theory. The results indicate synergism in the binary mixtures. Ideal and experimental critical micelle concentrations (i.e., cmc(*) and cmc) show nonideality, which is confirmed by beta values and activity coefficients. The micelle aggregation numbers (N(agg)), evaluated using steady-state fluorescence quenching at a total concentration of 2 mM for CTAB/16-4-16 or 16-6-16 and 5 mM for TTAB/16-4-16 or 16-6-16 systems, indicate that the contribution of conventional surfactants was always more than that of the geminis. The micropolarity, dielectric constant and binding constants (K(sv)) of mixed systems have also been evaluated from the ratios of respective peak intensities (I(1)/I(3) or I(0)/I(1)).     

Conformational study of the trinucleotide CpGpCp-pentapeptide Gly5 complex: The important role of bridging water in the complex formation

Conformational changes in the RNA-protein interaction were studied by calculating the intramolecular interaction energy of a model complex with the use of potential functions. The model complex has hydrogen-bonded water molecules bridging polypeptide NH groups to 2'-hydroxyl groups and sugar ring oxygen atoms. Since the sugar ring is constrained by the bridging water, preliminary calculations with the model compounds, the sugar ring, mononucleoside diphosphates, pCp and pGp, were carried out, and the flexibility and energetics of the sugar ring were compared with the previous results of DNA. The shift of the phase angle of the sugar ring occurred in the complex formation because of the hydrogen bond through the bridging water and the flexibility of the sugar ring. The free energy difference at 298 K is about ?74.0 kcal/mol which was obtained from the intramolecular interaction energy difference of ?67.5 kcal/mol by adding the conformational entropy change of 21.9 e.u., which in turn was calculated from the evaluation of the determinant of the matrix containing variances and covariances of the internal coordinates.