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Supramolecular complexation is an attractive strategy to modulate the performance of surfactants, e.g., by host-guest interactions. Here, we investigate the interaction of single-chained, di-, tri-, and tetrameric cationic surfactants with cyclodextrins by conductivity and 1H NMR measurements, exploring the effect of increasing the number of the surfactant hydrophobic tails on the stability of cyclodextrin:surfactant inclusion complexes. The stoichiometry and the binding equilibrium constants of the different inclusion complexes were elucidated. Under the working conditions, the number of hydrophobic chains was found not to affect stoichiometry and 1:1 inclusion complexes were formed for all the surfactants investigated. The stability of the host-guest complexes decreases from single-chained to dimeric (“gemini”) surfactants, the binding following a non-cooperative mechanism. This result may be rationalized by taking into account steric constraints and electrostatic effects as well as the need to overcome the hydrophobic interactions between the chains of the same surfactant molecule. However, a further increase in the number of hydrophobic tails, from two to three to four, results in an increase in the equilibrium binding constant, K1. In this case, an increment in the number of chains capable of interaction with the cyclodextrin molecules seems to be the main factor responsible for the increase in K1. ROESY spectra show the coexistence of different types of 1:1 host-guest complexes for tri- and tetrameric surfactants. Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía P12-FQM- 1105, FQM-274 y FQM-206 University of Seville 2017/1004 FEDER funds

The formation of calixarene-based liposomes was investigated, and the characterization of these nanostructures was carried out using several techniques. Four amphiphilic calixarenes were used. The length of the hydrophobic chains attached to the lower rim as well as the nature of the polar group present in the upper rim of the calixarenes were varied. The lipid bilayer was formed with one calixarene and with the phospholipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, DOPE. The cytotoxicity of the liposomes for various cell lines was also studied. From the results obtained, the liposomes formed with the least cytotoxic calixarene, (TEAC12)4, were used as nanocarriers of both nucleic acids and the antineoplastic drug doxorubicin, DOX. Results showed that (TEAC12)4/DOPE/p-EGFP-C1 lipoplexes, of a given composition, can transfect the genetic material, although the transfection efficiency substantially increases in the presence of an additional amount of DOPE as coadjuvant. On the other hand, the (TEAC12)4/DOPE liposomes present a high doxorubicin encapsulation efficiency, and a slow controlled release, which could diminish the side effects of the drug., This work was financed by the Consejería de Conocimiento, Innovación y Universidades de la Junta de Andalucía (FQM-206, FQM-274, and PY20-01234), the VI Plan Propio Universidad de Sevilla (PP2019/00000748), RTI2018-100692-B-100; P18-RT-1271; PI18-0005-2018; VI-PP AY.SUPLEM- 2019; RYC-2015-18670, The R+D+I grant PID2019-104195G from the Spanish Ministry of Science and Innovation-Agencia Estatal de Investigación/10.13039/501100011033 (P.H.) and the European Union (Feder Funds). The authors thank the University of Seville for the grant VPPI-US. J.A.L. also thanks the Fundación ONCE funded by the Fondo Social Europeo.

This article belongs to the Special Issue The Application of Nanocarriers in Therapeutic Agents., The obtaining of nanocarriers of gene material and small drugs is still an interesting research line. Side-effects produced by the toxicity of several pharmaceutics, the high concentrations needed to get therapeutic effects, or their excessive use by patients have motivated the search for new nanostructures. For these reasons, cationic metallo-liposomes composed by phosphatidylcholine (PC), cholesterol (CHO) and RuC1C19 (a surfactant derived from the metallic complex [Ru(bpy)3]2+) were prepared and characterized by using diverse techniques (zeta potential, dynamic light scattering and electronic transmission microscopy –TEM-). Unimodal or bimodal populations of spherical aggregates with small sizes were obtained depending on the composition of the liposomes. The presence of cholesterol favored the formation of small aggregates. ct-DNA was condensed in the presence of the liposomes investigated. In-vitro assays demonstrated the ability of these nanoaggregates to internalize into different cell lines. A positive gene transfection into human bone osteosarcoma epithelial cells (U2OS) was also observed. The RuC1C19 surfactant was used as sensor to quantify the binding of DNA to the liposomes. Doxorubicin was encapsulated into the metallo-liposomes, demonstrating their ability to be also used as nanocarriers of drugs. A relationship between then encapsulation percentage of the antibiotic and the composition of the aggregates has been established., This research was funded by the Ayudas a Consolidación de Grupos de la Junta de Andalucía (2019/FQM-206 and 2019/FQM-274) and the European Union (FEDER Funds). IVR’s lab is recipient of a Ramón y Cajal Contract RYC2015-18670, and supported by grants RTI2018-100692-B-I00, PI-0005-2018 and P18-RT-1271.

The interaction between calf-thymus DNA, ctDNA, and various single-chained surfac-tants with different functional groups at the end of hydrophobic tail was studied with the goal of investigating the influence of the functional group nature on surfactant DNA compacting effi-ciency. The surfactants investigated were dodecyltriethylammonium bromide (DTEABr), triethyl(1-phenoxydodecyl)ammonium bromide (12PhBr), triethyl(2-naphthoxydodecyl)ammonium bromide (12NBr) and 11-(isonicotinoyloxy)-N,N,N-triethyl-1-undecanaminium bromide (11PyBr). Results made evident that the surfactants’ tendencies to self-aggregation is the key factor determining their efficiency to compact the nucleic acid. Subsequently, DOPE/12NBr/pEGFP-C1 lipoplexes, with different cationic surfactant molar fractions (α) and mass ratios (L/D), were prepared and charac-terized. DOPE is a zwitterionic phospholipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, and the plasmid pEGFP-C1 carries a GFP coding sequence with the necessary regulatory elements for constitutive expression of the gene in human cells. 12NBr was chosen because it was the most efficient DNA compacting agent among the surfactants investigated. Finally, the cytotoxicity and transfection efficiency (TE) of DOPE/12NBr/pDNA lipoplexes, with different compositions, were investigated., This work was financed by the Consejería de Educación y Ciencia de la Junta de Andalucía (FQM-206 and FQM-274, and PI-0005-2018), the VI Plan Propio Universidad de Sevilla (PP2019/00000748), and the European Union (Feder Funds).

The interaction (adsorption process) of commercial ionic surfactants with non-functionalized and functionalized carbon nanotubes (CNTs) has been studied by potentiometric measurements based on the use of ion-selective electrodes. The goal of this work was to investigate the role of the CNTs&rsquo, charge and structure in the CNT/surfactant interactions. Non-functionalized single- (SWCNT) and multi-walled carbon nanotubes (MWCNT), and amine functionalized SWCNT were used. The influence of the surfactant architecture on the CNT/surfactant interactions was also studied. Surfactants with different charge and hydrophobic tail length (sodium dodecyl sulfate (SDS), octyltrimethyl ammonium bromide (OTAB), dodecyltrimethyl ammonium bromide (DoTAB) and hexadecyltrimethyl ammonium bromide (CTAB)) were studied. According to the results, the adsorption process shows a cooperative character, with the hydrophobic interaction contribution playing a key role. This is made evident by the correlation between the free surfactant concentration (at a fixed [CNT]) and the critical micellar concentration, cmc, found for all the CNTs and surfactants investigated. The electrostatic interactions mainly determine the CNT dispersion, although hydrophobic interactions also contribute to this process.

The self-aggregation of four amphiphilic cationic calix[4]arenes, CALIX, in aqueous solutions was investigated in this work. The nature of the polar group present at the upper rim as well as the length of the hydrophobic tails attached to the lower rim was varied. All the calixarenes present two critical aggregation concentrations, CAC1 and CAC2. For [CALIX] < CAC1 only micelles are present, within the range CAC1 < [CALIX] < CAC2 micelles as well as vesicles are observed, and for [CALIX] > CAC2 micelles and a wide distribution of vesicles were found. Cell viability experiments show that calixarene micelles and several of the calixarene vesicles investigated could be used as biocompatible nanocarriers. On this basis, the study of the interactions between the cationic calixarene aggregates (micelles and vesicles) and calf thymus DNA, ctDNA, were done and the results indicated that most of them strongly interact with the polynucleotide, inverting its charge. Micelles totally compact the ctDNA, while vesicles only partially cause conformational changes in the nucleic acid. Therefore, the CALIX micelles show potential as vectors in gene therapy. The encapsulation of the antineoplastic drug doxorubicin into the calixarene aggregates was also investigated. A high encapsulation efficiency was found for micelles and, specially, for vesicles. However, DOX-loaded calixarene vesicles present low stability at 37 °C, which is a serious restriction in their use as nanocarriers for this drug. The release of DOX from the calixarene micelles shows that they could lengthen the half-life of free doxorubicin in the body and, as a result, lower amounts of drug could be used in the cancer treatments diminishing the important side effects of DOX., This work was supported by the Consejería de Educación y Ciencia de la Junta de Andalucía (P12-FQM-1105, FQM-206 and FQM-274, and PI-0005-2018), the VI Plan Propio Universidad de Sevilla (PP2018-10338), the Ministerio de Ciencia, Innovación y Universidades (RTI2018-100692-B-I00), the grant Ramon y Cajal RYC2015-1867 and the European Union (Feder Funds). The authors thank the University of Seville for the grant VPPI-US.

Gene therapy is a therapeutic process consisting of the transport of genetic material into cells. The design and preparation of novel carriers to transport DNA is an important research line in the medical field. Hybrid compounds such as metallo-liposomes, containing a mixture of lipids, were prepared and characterized. Cationic metal lipids derived from the [Ru(bpy)3]2+ complex, RuC11C11 or RuC19C19, both with different hydrophobic/lipophilic ratios, were mixed with the phospholipid DOPE. A relation between the size and the molar fraction &alpha, was found and a multidisciplinary study about the interaction between the metallo-liposomes and DNA was performed. The metallo-liposomes/DNA association was quantified and a relationship between Kapp and &alpha, was obtained. Techniques such as AFM, SEM, zeta potential, dynamic light scattering and agarose gel electrophoresis demonstrated the formation of lipoplexes and showed the structure of the liposomes. L/D values corresponding to the polynucleotide&rsquo, s condensation were estimated. In vitro assays proved the low cell toxicity of the metallo-liposomes, lower for normal cells than for cancer cell lines, and a good internalization into cells. The latter as well as the transfection measurements carried out with plasmid DNA pEGFP-C1 have demonstrated a good availability of the Ru(II)-based liposomes for being used as non-toxic nanovectors in gene therapy.

In this work, the influence of the cyclodextrin, CD, nature on the decompaction of positively charged compacted dimeric surfactant-DNA complexes was investigated. First, the condensation of calf thymus DNA by addition of three cationic dimeric surfactants with different spacer groups was studied by fluorescence, zeta potential, circular dichroism and atomic force microscopy measurements. Electromotive force experiments provided quantitative information about the influence of the spacer group on the DNA surfactant compaction efficiency. Cytotoxicity was evaluated to determine the biocompatibility of the cationic lipids. Subsequently, the decompaction of the surfactant-DNA complexes was achieved by adding α-, β-, and γ-cyclodextrin, the experimental observations being analogous for the three surfactants investigated. α- and β-cyclodextrin were found to behave similarly. These CDs completely hinder the interactions between the surfactant and the nucleic acid and provoke the DNA morphological change from a globular to an elongated form. A concentration of γ-CD higher than those of α- or β-CD is necessary in order to decompact the nucleic acid. Besides, zeta potential measurements show that in the presence of γ-CD, surfactant-DNA interactions are only partially hindered, some of the surfactant molecules remaining bound to the DNA.

This study performed a biophysical characterization (electrochemistry, structure and morphology) and assessment of the biological activity and cell biocompatibility of GCL/DOPE-pDNA lipoplexes comprised of plasmid DNA and a mixed lipid formed by a DOPE zwitterionic lipid and a gemini cationic lipid N-N'-(1,3-phenylene bis (methylene)) bis (N,N-dimethyl-N-(1-dodecyl) ammonium dibromide (12PH12) containing an aromatic spacer or its monomeric counterpart surfactant, N-benzyl-N,N-dimethyl-N-(1-dodecyl) ammonium bromide (12PH). Electrochemical results reveal that i) the gemini cationic lipid (12PH12) and the plasmid pDNA yield effective charges less than their nominal charges (+2 and -2/bp, respectively) and that ii) both vectors (12PH12/DOPE and 12PH/DOPE) could compact pDNA and protect it from DNase I degradation. SAXS and cryo-TEM experiments indicate the presence of a lamellar lyotropic liquid crystal phase represented as alternating layers of mixed lipid and plasmid. Transfection efficiency (by FACS and luminometry) and cell viability assay in COS-7 cells, performed with two plasmid DNAs (pEGFP-C3 and pCMV-Luc VR1216), confirm the goodness of the proposed formulations (12PH12/DOPE and 12PH/DOPE) to transport genetic material, with efficiencies and biocompatibilities comparable to or better than those exhibited by the control Lipofectamine 2000*. In conclusion, although major attention has been paid to gemini cationic lipids in the literature, due to the large variety of modifications that their structures may support to improve the biological activity of the resulting lipoplexes, it is remarkable that the monomeric counterpart surfactant with an aromatic group analyzed in the present work also exhibits good biological activity. The in vitro results reported here indicate that the optimum formulations of the gene vectors studied in this work efficiently transfect plasmid DNA with very low toxicity levels and, thus, may be used in forthcoming in vivo experiments.

Reactivity under restricted geometry conditions can be quantitatively rationalized by using the Pseudophase Model. This model considers two states in equilibrium, free and bound, which are not perturbed by the reaction. That is, the reaction in which the two states participate must be slow in comparison to the exchange process between the free and bound states. This condition is fulfilled in the case of chemical reactions, but it does not hold for fast photochemical reactions. In spite of this, the Pseudo-phase Model was found to be, at least apparently, applicable for excited state reactions. However, a thorough analysis of the kinetic data brings to light important differences between the two types of reactions, particularly in the meaning of the parameters present in the equations of the Pseudophase Model.

The assembly of a surfactant-based rotaxane by adding the labile aquopentacyanoferrate(II) ion to the previously formed pseudorotaxane between the surfactant 11-(isonicotinoyloxy)-N,N,N-triethyl-1-undecanaminium bromide and β-cyclodextrin was investigated by 1H NMR and kinetic measurements. NMR spectroscopy has showed that the rotaxane can be formed through two different mechanisms. The rotaxane can be unstoppered by using the pyridine ligand substitution reaction by the high-field cyanide ligand. In this work a new method is developed for the preparation of several new surfactant-based rotaxanes by changing the hydrophilic and hydrophobic regions of the surfactants and the nature of the macrocycle.

The aim of this work was to investigate the influence of the incorporation of substituents at the end of the hydrophobic tail on the binding of cationic surfactants to α-, β-, and γ-cyclodextrins. The equilibrium binding constants of the 1:1 inclusion complexes formed follow the trend K1(α-CD) > K1(β-CD) ≫ K1(γ-CD), which can be explained by considering the influence of the CD cavity volume on the host-guest interactions. From the comparison of the K1 values obtained for dodecyltriethylammonium bromide, DTEAB, to those estimated for the surfactants with the substituents, it was found that the incorporation of a phenoxy group at the end of the hydrocarbon tail does not affect K1, and the inclusion of a naphthoxy group has some influence on the association process, slightly diminishing K1. This makes evident the importance of the contribution of hydrophobic interactions to the binding, the length of the hydrophobic chain being the key factor determining K1. However, the presence of the aromatic rings does influence the location of the host and the guest in the inclusion complexes. The observed NOE interactions between the aromatic protons and the CD protons indicate that the aromatic rings are partially inserted within the host cavity, with the cyclodextrin remaining close to the aromatic rings, which could be partially intercalated in the host cavity. To the authors’ knowledge this is the first study on the association of cyclodextrins with monomeric surfactants incorporating substituents at the end of the hydrophobic tail.

Given the high toxicity of the anthracycline antibiotic doxorubicin (DOX), it is relevant to search for nanocarriers that decrease the side effects of the drug and are able to transport it towards a therapeutic target Here, the encapsulation of DOX by p-sulfocalix[6]arene (calix) has been studied. The interaction of DOX with the macrocycle, as well as with DNA, has been investigated and the equilibrium constant for each binding process estimated. The results showed that the binding constant of DOX to DNA, KDNA , is three orders of magnitude higher than that to calix, Kcalix . The ability of calixarenes to encapsulate DOX molecules, as well as the capability of the DOX molecules included into the inner cavity of the macrocycle to bind with DNA have been examined. Cytotoxicity measurements were done in different cancer and normal cell lines to probe the decrease in the toxicity of the encapsulated DOX. The low toxicity of calixarenes has also been demonstrated for different cell lines.

The use of nanovectors in several medicinal treatments has reached a great importance in the last decade. Some drugs need to be protected to increase their lifetimes in the blood flow, to avoid degradation, to be delivered into target cells or to decrease their side effects. The goal of this work was to design and prepare nanovectors formed by novel surfactants derived from the [Ru(bpy)3]2+ complex. These amphiphilic molecules are assembled to form metallomicelles which can act as pharmaceutical agents and, at the same time, as nanovectors for several drugs. TEM images showed a structural transition from spherical to elongated micelles when the surfactant concentration increased. Fluorescence microscopy confirmed the internalization of these metallomicelles into diverse cell lines and cytotoxicity assays demonstrated specificity for some human cancer cells. The encapsulation of various antibiotics was carried out as well as a thorough study about the DNA condensation by the metallomicelles. To the best of our knowledge, applications of these metallomicelles have not been shown in the literature yet., This work was supported by the Consejería de Educación y Ciencia de la Junta de Andalucía (Proyecto de Excelencia P12-FQM-1105, FQM-206 and FQM-274), the VI Plan Propio Universidad de Sevilla (2018/500) and the European Union (Feder Funds). The authors thank the University of Seville for the grant VPPI-US.

Cefepime is an antibioticwith a broad spectrumof antimicrobial activity. However, this antibiotic has several side effects and a high degradation rate. For this reason, the preparation and characterization of new liposomes that are able to encapsulate this antibiotic seemto be an important research line in the pharmaceutical industry. Anionic and cationic liposomes were prepared and characterized. All cationic structures contained the same cationic surfactant, N,N,N-triethyl-N-(12-naphthoxydodecyl)ammonium. Results showed a better encapsulation-efficiency percentage (EE%) of cefepime in liposomes with phosphatidylcholine and cholesterol than with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The presence of cholesterol and the quantity of egg-yolk phospholipid in the liposome increased the encapsulation percentage. The bactericidal activity against Escherichia coli of cefepime loaded into liposomes with phosphatidylcholinewasmeasured. The inhibitory zone in an agar plate for free cefepimewas similar to that obtained for loaded cefepime. The growth-rate constant of E. coli culture was also measured in working conditions. The liposome without any antibiotic exerted no influence in such a rate constant. All obtained results suggest that PC:CH:12NBr liposomes are biocompatible nanocarriers of cefepime that can be used in bacterial infections against Escherichia coli with high inhibitory activity., This research was funded by the Consejeria de Educacion y Ciencia de la Junta de Andalucia (Proyecto de Excelencia P12-FQM-1105, FQM-206 and FQM-274), the VI Plan Propio Universidad de Sevilla (2018/500), and the European Union (Feder Funds).

The insertion of biocompatible amino acid moieties in non-viral gene nanocarriers is an attractive approach that has been recently gaining interest. In this work, a cationic lipid, consisting of a lysine-derived moiety linked to a C12 chain (LYCl) was combined with a common fusogenic helper lipid (DOPE) and evaluated as a potential vehicle to transfect two plasmid DNAs (encoding green fluorescent protein GFP and luciferase) into COS-7 cells. A multidisciplinary approach has been followed: (i) biophysical characterization based on zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and cryo-transmission electronic microscopy (cryo-TEM), (ii) biological studies by fluorescence assisted cell sorting (FACS), luminometry, and cytotoxicity experiments, and (iii) a computational study of the formation of lipid bilayers and their subsequent stabilization with DNA. The results indicate that LYCl/DOPE nanocarriers are capable of compacting the pDNAs and protecting them efficiently against DNase I degradation, by forming L&alpha, lyotropic liquid crystal phases, with an average size of ~200 nm and low polydispersity that facilitate the cellular uptake process. The computational results confirmed that the LYCl/DOPE lipid bilayers are stable and also capable of stabilizing DNA fragments via lipoplex formation, with dimensions consistent with experimental values. The optimum formulations (found at 20% of LYCl content) were able to complete the transfection process efficiently and with high cell viabilities, even improving the outcomes of the positive control Lipo2000*.

Aquaculture is threatened by severe bacterial and viral outbreaks which can cause massive mortality and limit productivity. Antimicrobial peptides are a promising tool for the control of infectious diseases; however, their use in the aquaculture sector has been poorly explored. Recombinant production of peptides is an interesting alternative to their chemical synthesis, which has still important challenges to address. Although extra amino acid tags are usually added to the ends of recombinant proteins to enhance their stability and facilitate their purification or their translational processing, the effect of these tags on the function and the stability of antimicrobial peptides is completely unknown. This is particularly important in the case of the short cationic antimicrobial peptide caerin, originally isolated from frog skin secretions, and other peptides which bioactivity has been directly related with its ability to adopt an amphipathic alpha-helical structure upon interaction with the microbial membranes. Caerin has demonstrated bactericidal activity against several important human pathogens, however its antimicrobial activity over usual aquaculture pathogens remains practically unexplored. In the present work, we have studied the effect of adding the terminal tag polyhistidine (6xHis) and the 2A peptide from the foot and mouth disease virus (FMDV-2A) to the N- or the C- terminus of caerin on its activity against a collection of bacterial and viral pathogens common to aquaculture species. In addition, the antimicrobial activity of a peptide composed of two tandem consecutive caerin sequences has been investigated. We have concluded that the addition of terminal tags to caerin causes a drastic reduction of its antiviral activity against the studied viruses and that the effect of the added tags on the bactericidal activity of the peptide depends of the target bacterial species. However, caerin with a 6xHis extension at its N terminus maintains or increases its antimicrobial activity against most of the fish pathogenic bacteria tested. According to our data, there is only a moderate agreement between the theoretical predictions obtained from in silico models and the experimental observations. This information is essential for the rational design of strategies to aim the recombinant production of caerin and other antimicrobial peptides, which can be used as anti-infective agents in aquaculture.

Several cationic dimeric surfactants have shown high affinity towards DNA. Bis-quaternary ammonium salts (m-s-m) have been the most common type of dimeric surfactants investigated and it is generally admitted that those that posses a short spacer (s ≤ 3) show better efficiency to bind or compact DNA. However, experimental results in this work show that 12-s-12 surfactants with long spacers make the surfactant/ctDNA complexation more favorable than those with short spacers. A larger contribution of the hydrophobic interactions, which control the binding Gibbs energy, as well as a higher average charge of the surfactant molecules bound to the nucleic acid, which favors the electrostatic attractions, could explain the experimental observations. Dimeric surfactants with intermediate spacer length seem to be the less efficient for DNA binding.

Potentiometric measurements based on the use of ion-selective electrodes have been used to study the interaction (adsorption) of anionic and cationic surfactants with functionalized single-walled carbon nanotubes (SWCNT–COOH). According to results, the interaction is driven by hydrophobic forces between the hydrocarbon tails of the surfactants and the nanotube walls. Electrostatic interactions practically exert no influence on the interaction. Driving forces in the dispersion processes are different. Keywords: Ion-selective electrodes, Carbon nanotubes, Surfactants, Interaction, Dispersion, Driving forces

López-López, Manuel et al., The goal of this work was to understand the key factors determining the DNA compacting capacity of single-chained cationic surfactants. Fluorescence, zeta potential, circular dichroism, gel electrophoresis and AFM measurements were carried out in order to study the condensation of the nucleic acid resulting from the formation of the surfactant-DNA complexes. The apparent equilibrium binding constant of the surfactants to the nucleic acid, K, estimated from the experimental results obtained in the ethidium bromide competitive binding experiments, can be considered directly related to the ability of a given surfactant as a DNA compacting agent. The plot of ln(K) vs. ln(cmc), cmc being the critical micelle concentration, for all the bromide and chloride surfactants studied, was found to be a reasonably good linear correlation. This result shows that hydrophobic interactions mainly control the surfactant DNA compaction efficiency., This work was financed by the Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía (P12-FQM-1105), FQM-274 and FQM-206, University of Seville (2017/1004), R+D+i grant from the Spanish Ministry of Economy and Competitivity (SAF2013-43255 and SAF2016-74855) and FEDER funds.

The micellization of four dimeric cationic surfactants (“gemini surfactants”) derived from N-dodecyl-N,N,N-trimethylammonium chloride was studied in pure water and in water–ionic liquid (IL) solutions by a wide range of techniques. The dimeric surfactants are distinguished by their rigid spacer groups separating the two surfactant motifs, which range from C3 to C5 in length. In order to minimize organic ion pairing effects as well as the role of the ionic liquids as potential co-surfactants, ILs with inorganic hydrophilic anions and organic cations of limited hydrophobicity were chosen, namely ethyl, butyl, and hexyl-3-imidazolium chlorides. 1H NMR two-dimensional, 2D, rotating frame nuclear Overhauser effect spectroscopy measurements, ROESY, supported this premise. The spacer nature hardly affects the micellization process, neither in water nor in water–IL solutions. However, it does influence the tendency of the dimeric surfactants to form elongated micelles when surfactant concentration increases. In order to have a better understanding of the ternary water–IL surfactant systems, the micellization of the surfactants was also studied in aqueous NaCl solutions, in water–ethylene glycol and in water–formamide binary mixtures. The combined results show that the ionic liquids play a double role in the mixed systems, operating simultaneously as background electrolytes and as polar organic solvents. The IL role as organic co-solvent becomes more dominant when its concentration increases, and when the IL alkyl chain length augments.

The aggregation process of sodium cholate, NaC, sodium deoxycholate, NaDC, sodium glycocholate, NaG, sodium glycodeoxycholate, NaDG, sodium taurocholate, NaT, and sodium taurodeoxycholate, NaDT in aqueous solution has been investigated at several temperatures, in the absence and in the presence of NaCl 0.15 mol kg–1. Results show that both a decrease in the number of ring hydroxyls and an increase in the length of the side chain favor micellization, in the absence as well as in the presence of salt. These observations can be explained by considering that the hydrophobic effect is the driving force for the self-association process. This is in agreement with the ΔmicCp° values, which point out that the micellization process leads to a diminution of the hydrophobic surface of the bile salt molecules exposed to water. The presence of NaCl 0.15 mol kg–1 in the aqueous phase favors micellization by decreasing the CMC due to a diminution in the electrostatic repulsions within the micelles. However the presence o...

The interactions between bovine serum albumin (BSA) and the single-chain surfactants N-benzyl-N,N-dimethyl-N-(1-dodecyl)ammonium bromide (PH12) and N-cyclohexylmethyl-N,N-dimethyl-N-(1-dodecyl)ammonium bromide (CH12) and their two dimeric counterparts, N,N'-[1,3-phenylenebis(methylene)]bis[N,N-dimethyl-N-(1-dodecyl)]ammonium dibromide (12PH12) and N,N'-[cyclohexane-1,3-diylbis(methylene)]bis[N,N-dimethyl-N-(1-dodecyl)]ammonium dibromide (12CH12), respectively, have been investigated by surface tension, fluorescence, circular dichroism, ζ potential, and atomic force microscopy. The results obtained permit the examination of the way an increase in the number of hydrophobic chains and the substitution of a cyclohexyl ring by a phenyl ring, either in the headgroup of single-chain surfactants or in the spacer of dimeric surfactants, affect BSA-surfactant interactions. The comparison of the fluorescence results with those obtained by ζ potential measurements shows that the sites of binding of the surfactants with aromatic rings to the BSA are somewhat different from those of the surfactants with no aromatic rings.

Micellization in the aqueous binary mixtures of n-decanoyl N-methylglucamide, MEGA10, and alkanediyl-α,ω-bis(dodecyldimethylammonium) bromide, 12-s-12 (with s = 7, 9, 11), was investigated at 303 K and the data compared to those previously found in MEGA10-12-s-12 mixed solutions, with s = 2, 3, 4, 5, 6, 8, 10, and 12. Application of different theoretical approaches to the binary mixtures showed a non ideal behavior, the spacer length not affecting substantially the Rubingh interaction parameter. However, circular dichroism experiments show and odd–even effect in the interactions of the dimeric surfactants with MEGA10 molecules within the mixed micelles. Micellar growth was also studied in the mixed micellar solutions, the addition of MEGA10 diminishing the tendency of the dimeric aggregates to form elongated micelles upon increasing surfactant concentration.

In this work, three didodecyl dicationic dibromide dimeric surfactants 12-s-12, 2Br−, with different methylene spacer lengths (s = 7, 9, and 11) were prepared and characterized and their properties compared to those of 12-s-12, 2Br− surfactants with s = 2, 3, 4, 5, 6, 8, 10, and 12. Information about the critical micelle concentration, the micellar ionization degree, the average aggregation number and the polarity of the interfacial region, and microviscosity of the micellar interior was obtained by using different techniques. Their surface activity was investigated by means of surface tension measurements. Micellization was also studied by using 1H NMR and diffusion NMR (DOSY) spectroscopy as well as isothermal titration calorimetry. The values of the thermodynamic parameters show that the dimeric surfactants micellization is exothermic and driven by entropy. The occurrence of morphological transitions upon increasing surfactant concentration was studied, and the results indicate that the spacer length, s, plays a key role in the micellar growth of 12-s-12, 2Br− aggregates. The value of s not only control the magnitude of C*, the surfactant concentration above which the morphological transition from spherical micelles into elongated ones occurs, but also the sign of the enthalpy change accompanying the sphere-to-rod transition.

The bimolecular reactions methyl naphthalene-2-sulfonate + Br − , MNS + Br − , and 2-(4-nitrophenyl) ethyl bromide + OH − , PEB + OH − , were studied in micellar solutions of cationic monomeric and dimeric surfactants with phenyl and cyclohexyl rings in the head group. Morphological transitions occur in these micellar solutions when surfactant concentration increases. A kinetic equation based on the pseudophase model could not quantitatively explain the kinetic micellar effects on the process MNS + Br − . Micellar growth brings about a decrease in the micellar ionization degree which has to be considered in order to explain the experimental kinetic data. Besides, the formation of elongated micelles is followed by changes in the characteristics of the interfacial region which can affect the equilibrium binding constant as well as the second order rate constant at the micellar pseudophase. These medium micellar effects are larger the stronger the tendency of the surfactant to micellar growth is. The kinetic micellar effects on the reaction PEB + OH − were quantitatively rationalized by considering a kinetic equation based on the ion-exchange pseudophase model. This could be taken as indicative that the equilibrium ion-exchange constant controlling the exchange between the surfactant counterion, Br − , and OH − at the micellar surface does not substantially change with micellar growth. The effects of the number of alkyl chains and of the nature of the ring present in the head group on reactivity were explained by considering their influence on the polarity of the interfacial region and on the tendency of the micelles to grow.

The SN2 substitution reactions between methyl naphthalene-2-sulfonate and methyl 4-nitrobenzenesulfonate with bromide ions were studied in alkanediyl-α,ω-bis(dimethyldodecylammonium) bromide, 12-s-12,2Br− (s = 3, 4, 6), micellar solutions in the absence and in the presence of alcohols. The observed rate constant for the two processes was found to be sensitive to changes in micellar characteristics caused by the presence of alcohols. At high surfactant concentrations, kinetic data made evident the sphere-to-rod transition accompanying the increase in the dimeric surfactant concentration in all the micellar reaction media investigated. Kinetic results were quantitatively rationalized within the whole surfactant concentration range, below and above the second CMC, by using a new treatment based on the pseudophase kinetic model.

The reaction methyl naphthalene-2-sulfonate + Br(-) was investigated in several alkanediyl-α-ω-bis(dodecyldimethylammonium) bromide, 12-s-12,2Br(-) (with s = 2, 3, 4, 5, 6, 8, 10, 12), micellar solutions in the absence and in the presence of various additives. The additives were 1,2-propylene glycol, which remains in the bulk phase, N-decyl N-methylglucamide, MEGA10, which forms mixed micelles with the dimeric surfactants, and 1-butanol, which distributes between the aqueous and micellar phases. Information about the micellar reaction media was obtained by using conductivity and fluorescence measurements. In all cases, with the exception of water-1,2-prop 12-5-12,2Br(-) micellar solutions, with 30% weight percentage of the organic solvent, a sphere-to-rod transition takes place upon increasing surfactant concentration. In order to quantitatively explain the experimental data within the whole surfactant concentration range, a kinetic equation based on the pseudophase kinetic model was considered, together with the decrease in the micellar ionization degree accompanying micellar growth. However, theoretical predictions did not agree with the experimental kinetic data for surfactant concentrations above the morphological transition. An empirical kinetic equation was proposed in order to explain the data. It contains a parameter b which is assumed to account for the medium micellar kinetic effects caused by the morphological transition. The use of this empirical equation permits the quantitative rationalization of the kinetic micellar effects in the whole surfactant concentration range.

Micellization and micellar growth of cationic dimeric surfactants of the alkanedyil-α,ω-bis(dimethyldodecylammonium) bromide type, 12-s-12,2Br− (s = 3, 4, 6), in the presence of various amounts of 1-butanol, 1-pentanol, and 1-hexanol have been investigated. The influence of the nature and concentration of alcohol on the cmc, on the micellar ionization degree, on the average micellar aggregation number, and on the polarity of the micellar interfacial region was investigated by using conductivity and fluorescence measurements. Subsequently, effects of alcohol addition on the surfactant concentration range where sphere to rod transitions occur were examined and information about changes in the micropolarity and in the microviscosity accompanying the morphological transition was obtained. The experimental results were explained by considering the variations in the different contributions to the Gibbs energy of micellization caused by the presence of alcohols. The study of the reaction methyl naphthalene-2-sulfonate + Br− in some water–alcohol 12-6-12,2Br− micellar solutions provided information about the characteristics of the dimeric micelles as microreactors and show the complexity of the microheterogeneous systems studied.

Aggregation of tetradecyltrimethylammonium bromide, TTAB, in mixed solvent systems containing ethylene glycol, EG, 1,2-propylene glycol, 1,2-PROP, 1,3-propylene glycol, 1,3-PROP, and tetraethylene glycol, TEG, has been investigated by employing conductivity and fluorescence methods. Gibbs energies of micellization were determined in order to evaluate the effects of the co-solvent on the aggregation process. Information about the influence of the organic solvent on the surfactant adsorption at the air-solution interface, on the micellar size and on the polarity of the micellar interfacial region was obtained by means of surface tension and fluorescence measurements. The study of the reaction methyl naphthalene-2-sulfonate + Br - in the water–glycol TTAB micellar solutions provided information about the characteristics of TTAB micelles as microreactors in the water–solvent binary mixtures.

Effects of ethylene glycol (EG) addition on the micellization and on the micellar growth in two aqueous didodecyl dicationic dibromide surfactant, 12-s-12,2Br- (s=2, 6) solutions, with the weight percentage of EG up to 50%, have been investigated. An increment in the amount of EG makes the aggregation process less spontaneous due to the water-EG mixtures being better solvents for the cationic dimeric surfactant molecules than pure water (solvophobic effect). Results show that C*, the surfactant concentration where the sphere-to-rod transition occurs, increases when EG content in the bulk phase increases. The amount of the organic solvent influences C* principally through the decrease in the hydrocarbon/bulk phase interfacial tension (air/bulk phase surface tension) caused by its presence. Changes in the aggregation number, in the micropolarity, in the microviscosity, and in the rheological behavior accompanying micellar growth were studied in the water-EG micellar solutions. Kinetic studies provide information about the characteristics of the dimeric micelles as microreactors. Kinetic data also show that an increase in the surfactant concentration leads to micellar growth.

The reaction between methyl 4-nitrobenzenesulfonate and bromide ions has been studied in mixed single-chain-gemini micellar solutions of n-dodecyltrimethylammonium bromide, DTAB, and dodecyl tricosaoxyethylene glycol ether, Brij35, with alkanediyl-α-ω-bis(dodecyldimethylammonium) bromide, 12-s-12,2Br− ( s = 3 , 4 , 5 ). Kinetic micellar effects show that an increase in the solution mole fraction of the single-chain surfactant, X single - chain , results in a diminution of the mixed micelles tendency to form spherocylindrical aggregates upon increasing surfactant concentration. The dependence of the surfactant concentration at which the sphere-to-rod transition occurs, C ∗ , on X single - chain showed through kinetic data was in agreement with results obtained by means of fluorescence measurements.

Critical micelle concentrations of the Cm TAB+12- s-12 (s=3, 4, 5 and m=10, 12, 14, 16) binary systems have been determined, through conductivity and fluorescence measurements, at 298 K. Application of different theoretical approaches to explain mixed micellization shows that non-ideality of the binary systems follows the trend C16TAB+12-3-12

Experimental data of amphiphiles aggregation phenomena in water-organic solvent mixtures were considered with the idea of investigating the role of the solvophobic effect on micellization. Changes in the critical micelle concentration, in the micellar ionization degree (for ionic surfactants) and in the aggregation number accompanying variations in the composition of the bulk phase of the micellar solutions were examined with the scope of understanding which properties of the water-organic solvent mixtures are important in the micellization process. Results point out that the cohesive energy density, measured either through the Hildebrand-Hansen solubility parameter or the Gordon parameter, seems to play an important role in determining the contribution of the solvophobic effect on the Gibbs energy of micellization in water-organic solvents mixtures.

The reactions 4-nitrobenzenesulfonate + Br− and methyl naphthalene-2-sulfonate + Br− were studied in various water–ethylene glycol, EG, [C12H25(CH3)2N (CH2)sN(CH3)2C12H25]Br2 micellar solutions (12-s-12,2Br− with s = 3 – 5 methylene groups). Results showed that the observed rate constant of the two reactions varied when a sphere-to-rod transition occurs. This morphological transition is accompanied by changes in the interfacial region water content and in its polarity. The micellar ionization degree is also altered, making the counterion interfacial concentration change. Finally, variations on the molar surfactant volume, V m , also follow the sphere-to-rod transitions. A simple pseudophase kinetic model is inadequate for quantitatively discussing the kinetic micellar effects observed, since the changes accompanying micellar growth affect the second-order rate constant in the micellar pseudophase, the equilibrium binding constant and the surfactant molar volume, neither of them remaining constant in the whole surfactant concentration range. However, this simple model can be helpful in the treatment of kinetic data for surfactant concentrations below the morphological transitions, providing some interesting, although approximate, information.

Micellization of cetyltrialkylammonium bromide (alkyl = methyl, ethyl, propyl, and butyl) surfactants has been studied in various water–ethylene glycol, EG, mixtures. This study provided the opportunity of investigating how, for a given hydrophobic tail length, the head group size determines the effect of the addition of EG on the micellization process. Conductivity, surface tension, spectroscopic and steady-state fluorescence measurements were carried out. The influence of additional methylenes in the headgroups on the Gibbs energy of micellization, Δ G M ° , was found to derive from changes in the solvophobic Gibbs energy contribution and from variations in the electrostatic headgroups interaction contribution.

Free radical scavenging activity of different polyphenolic compounds commonly present in wine has been evaluated using DPPH method. The experiments were performed with different amounts of phenols within the linear interval of response and with an excess of DPPH in all cases. In these conditions, for most of the compounds tested, the reaction was biphasic. Total stoichiometry values n confirm the implication of more than one step in the process. Flavan-3-ol compounds showed the highest values, especially procyanidins B1 (9.8) and B2 (9.1). In this family, n values coincide with the number of hydroxyl groups available. EC(50) and TEC(50) parameters have been calculated. EC(50) values are extremely diverse, being the procyanidins B1 and B2 the most potent scavenging compounds and resveratrol the less one. TEC(50) considers the rate of reaction towards the free radical. (+)-Catechin and (-)-epicatechin are the phenolic compounds that need more time to react. In contrast, caftaric and caffeic acids are the phenolic acids that react more rapidly. Antioxidant efficacy (AE) is a parameter that combines both factors. Compounds as kaempferol, with a high EC(50) value, could be considered as an antioxidant with low relevance, but instead shows the highest AE value of the phenolic compounds tested, due to its fast rate of reaction, what is of great biological importance.

With the idea of improving and advancing the design and preparation of new reagents based on cationic surfactants for gene therapy, two luminescent metallosurfactants derived from the [Ru(2,2'-bpy)3](2+) complex were synthesized. Their interaction with DNA and the effect they exert on the conformation of the polynucleotide were studied by using different techniques. The equilibrium binding constants, Kb, of the two surfactants to DNA were obtained at different molar ratios X=[surfactant]/[DNA]. The observed sigmoidal dependence of Kb on X confirms the cooperative character of the binding. After the addition of a determined surfactant concentration, the condensation of the polymer was observed. The amount of surfactant needed to produce this conformational change is lower for the double stranded surfactant than for the single chain surfactant due to a stronger hydrophobic interaction. The addition of α-cyclodextrin molecules to the metallosurfactant/DNA solutions results in polynucleotide decompaction, which confirms the importance of the hydrophobic interactions in the condensation of the polynucleotide. Results also show the importance of choosing both a proper system to study and the most seeming measuring technique to use. It is demonstrated that, in some cases, the use of several techniques is desirable to obtain reliable and accurate results.

A study of a dinitro-diester calix[4]arene (5,17-(3-nitrobenzylideneamino)-11,23-di-tert-butyl-25,27-diethoxycarbonyl methyleneoxy-26,28-dihydroxycalix[4]arene) interaction with calf-thymus DNA was carried out using several techniques. The measurements were done at various molar ratios X=[calixarene]/[DNA]. Results show diverse changes in the DNA conformation depending on the X value. Thus, at low macrocycle concentrations, the calixarene binds to the polynucleotide. This interaction, mainly in groove mode, weakens the hydrogen bonds between base pairs of the helix inducing denaturation of the double strands, as well as condensation of the macromolecule, from an extended coil state to a globular state. An opposite effect is observed at X molar ratios higher than 0.07. The de-condensation of DNA happens, that is, the transition from a compact state to a more extended conformation, probably due to the stacking of calixarene molecules in the solution. Results also show the importance of making a proper choice of the system under consideration. Junta de Andalucía P08-FQM-03623, P12-FQM-1105

The reaction methyl 4-nitrobenzenesulfonate + Br- was studied in water-formamide tetradecyltrimethylammonium bromide micellar solutions. A pseudophase kinetic model was used to quantitatively rationalize the kinetic micellar effects observed