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Surfactant-based nanostructures are promising materials for designing novel colorimetric biosensors based on aggregation/disaggregation phenomena. In this work, a colorimetric sensor based on the plasmonic shift of surfactant-capped gold nanoparticles via the disaggregation mechanism was developed. To perform this, the optimum SDS concentration was firstly determined in order to form Au@16-s-16/SDS complex aggregates with a well-defined SPR band in the blue region. Once the optimal SDS concentration for Au@16-s-16 aggregation was established, the sensing method depended on the nature of the electrostatic charge of the biopolymer studied where both the strength of the biopolymer/SDS and biopolymer/Au@16-s-16 interactions and the cationic gold nanoparticles play a key role in the disaggregation processes. As a result, an instantaneous color change from blue to red was gradually observed with increasing biopolymer concentrations. The response of the sensor was immediate, avoiding problems derived from time lapse, and highly dependent on the order of addition of the reagents, with a detection limit in the nanomolar and picomolar range for DNA and Lysozyme sensing, respectively. This behavior can be correlated with the formation of different highly stabilized Au@16-s-16/biopolymer/SDS complexes, in which the particular biopolymer conformation enhances the distance between Au@16-s-16 nanoparticles among the complexes.

Different gold nanosystems covered with DNA and doxorubicin (Doxo) were designed and synthesized for cancer therapy, starting from Au@16-Ph-16 cationic nanoparticles and DNA–Doxo complexes prepared under saturation conditions. For the preparation of stable, biocompatible, and small-sized compacted Au@16-Ph-16/DNA–Doxo nanotransporters, the conditions for the DNA–Doxo compaction process induced by gold nanoparticles were first explored using fluorescence spectroscopy, circular dichroism and atomic force microscopy techniques. The reverse process, which is fundamental for Doxo liberation at the site of action, was found to occur at higher CAu@16-Ph-16 concentrations using these techniques. Zeta potential, dynamic light scattering and UV–visible spectroscopy reveal that the prepared compacted nanosystems are stable, highly charged and of adequate size for the effective delivery of Doxo to the cell. This fact is verified by in vitro biocompatibility and internalization studies using two prostate cancer-derived cell lines (LNCaP and DU145) and one hepatocellular carcinoma-derived cell line (SNU-387), as well as a non-tumor prostate (PNT2) cell line and a non-hepatocarcinoma hepatoblastoma cell line (Hep-G2) model used as a control in liver cells. However, the most outstanding results of this work are derived from the use of the CI+NI combined treatments which present strong action in cancer-derived cell lines, while a protective effect is observed in non-tumor cell lines. Hence, novel therapeutic targets based on gold nanoparticles denote high selectivity compared to conventional treatment based on free Doxo at the same concentration. The results obtained show the viability of both the proposed methodology for internalization of compacted nanocomplexes inside the cell and the effectiveness of the possible treatment and minimization of side effects in prostate and liver cancer.

The interaction between calf thymus DNA and the gemini surfactants N,N'-[α,ω-phenylenebis(methylene)bis [N,N'-dimethyl-N-(1-hexadecyl)]-ammonium dibromide], p-16-Ph-16 (α = 1, ω = 3) and m-16-Ph-16 (α = 1, ω = 2), has been investigated via circular dichroism, fluorescence and UV-vis spectroscopy, zeta potential, dynamic light scattering, and AFM microscopy. Measurements were carried out in aqueous media at different molar ratios, R = (C16-Ph-16)/CDNA and C16-Ph-16 always below the critical micellar concentration (CMC) of the surfactant. Under these conditions, DNA undergoes two reversible conformational changes, compaction and decompaction, due to interaction with the surfactant molecules at low and high molar ratios, respectively. The extent of such conformational changes is correlated with both the degree of surfactant partial intercalation, and the size and charge of the surfactant aggregates formed, in each case. Comparison of the results shows that the para-form of the surfactant intercalates into the DNA to a major extent; therefore, the compaction/decompaction processes are more effective. Among these, the structure of the resulting 16-Ph-16/DNA decompacted complex is worthy of note. For the first time it can be demonstrated that the partial intercalation of the 16-Ph-16 gemini surfactants induces the formation of triplex DNA-like structures at a high R ratio.

Diisopropyl allyloxymethylphosphonate prepared by a one-pot procedure was isomerized to give racemic 1-hydroxy-3-butenylphosphonate with LDA by a [2,3]-sigmatropic rearrangement. Chloroacetylation delivered an ester, which was resolved in a two-phase system by using the lipase from Thermomyces lanuginosus. Racemic and (S)-α-hydroxyphosphonate 6 were converted to (±)- and (R)-phosphaaspartic acid by functional-group manipulation. (±)-, (R)- and (S)-6 were first esterified with 4-nitrobenzenesulfonyl chloride before hydroboration to transform the double bond into a hydroxyethyl group. The hydroxyl group was manipulated to give a guanidinyl group and the 4-nitrobenzenesulfonyloxy to give an amino group. Global deprotection of the α-aminophosphonates yielded the desired phosphaamino acids.

MicroRNAs (miRNAs) provide a unique mechanism of gene regulation and play a key role in different pathologies ranging from metabolic diseases to cancer. Thus, they are attractive candidates as therapeutic targets in the clinic. However, delivering miRNAs to specific tissues remains challenging, due to their inherent instability and their low diffusion into tissues, as well as a lack of effective means of delivering them to the cytosols of the specific cells. To overcome these challenges, we constructed a delivery vehicle based on novel gold nanosystems having gemini surfactants which offer a high capacity to induce the miRNAs compression, high stability and cell-entry capability. The synthesis of gold nanoparticles with a positive surface charge, Au@16-Ph-16/miR-21 and Au@16–3-16/miR-21, was carried out in a three-step process. In this method, the hydrogen tetrachloroaurate, sodium tetrahydroborate and 16-Ph-16 or 16–3-16 compounds were used as gold precursor, reducing agent and stabilizers, respectively. The nanoparticles obtained were then covered with miR-21 polymer and were characterized by UV–visible spectroscopy, transmission electron microscopy, atomic force microscopy, dynamic light scattering and zeta potential to measure size and charge distribution. Finally, toxicity was assessed in vivo in mice. Moreover, coherent anti-Stokes Raman spectroscopy and histochemistry analyses showed that Au@16-Ph-16/miR-21 and Au@16–3-16/miR-21 exhibited no toxicity, antimicrobial and biocompatible activities. These nanosystems can be a valuable alternative in therapies associated with diseases where miRNAs play a regulatory role that may be decisive in the improvement or cure of patients. All these characteristics could make of these nanosystems the best potential therapeutic molecules.

A series of cationic gemini surfactants containing different spacer length were synthesized and analyzed structurally. It was shown that the surface tension (σ) and critical micelle concentration (CMC), which had a maximum for the n-C4H8 spacer depended on the spacer length. The foaming ability and foam stability are high for the gemini surfactants with short spacers (C2H4 to n-C4H8), while longer spacers lead to a distinct decrease of these foam parameters. Foaming properties are discussed in terms of configuration and conformation of a surfactant molecule and in relation to micellization state kinetic.

Three series of the gemini surfactants (diquaternary amines) anionic clusters with formate or bromide anions were studied in the gas phase by ER-MS on triple quadrupole mass spectrometer. The gemini series were: alkanediyl-α,ω-bis-(N,N-dimethyl-N-dodecyl ammonium), alkanediyl-α,ω-bis-(N-hydroxyethyl-N-methyl-N-dodecyl ammonium) and oligo(oxa)ethyl-α,ω-bis-(N,N-dimethyl-N-dodecyl ammonium), where the alkyl spacer size was from 2 to 12 methyl groups, and the oxaethyl range was from 2 to 8 units. The clusters were formed by one dication and three anions with formulas: [MBr3]−, [MBr2HCOO]−, [MBr(HCOO)2]− and [M(HCOO)3]−. Collisions induced internal reactions: nucleophilic substitutions SN2 at nitrogen α-carbons, eliminations E2, and hydrogen transfer from hydroxy group to the anion. By quantitative determination of the amounts of fragments in each dissociation channel and by plotting the ratios in function of the spacer lengths it was found that the clusters with short and long spacers formed two distinct reaction patterns. By comparisons to the cationic cluster reactions it was found that crowding inside the anionic cluster caused by the extra anions makes them to reacts through pathways they avoided in cationic clusters. Mixed anion clusters were determined to produce the same sets of fragments as homogeneous clusters in the amount which roughly corresponds to the increment of a given anion; on these bases, it was decided that anions are mobile in the cluster prior to dissociation reaction. When ethyloxy group in the mixed cluster was one of the nitrogen substituents a slight preference was toward formate anion products was observed, which was explained by formation of hydrogen bonding.

Fragmentation by collisionally induced dissociation in triple quadrupole mass spectrometer of pairs of six series of quaternary diamines (gemini surfactants) with two anions: formate and bromide has been studied. Amines included alkanediyl-α,ω-bis-(N,N-dimethyl-N-dodecyl ammonium bromide), alkanediyl-α,ω-bis-(N-hydroxyethyl-N-methyl-N-dodecyl ammonium bromide), oligo(oxa)ethyl-α,ω-bis-(N,N-dimethyl-N-dodecyl ammonium bromide) and three series of hexadecyl homologues. Range of atoms forming spacer varied from 2 to 23. It was confirmed that fragmentation occurs via either nucleophilic substitution or elimination reactions. All possible α-carbon atoms can be attacked in the substitution reaction, so can be all possible hydrogens of β-carbon in the elimination reaction. Additionally transferred to anion can be hydroxy group hydrogen. It leads together to eight different reaction paths. Depending on the spacer size and the kind of anion the ratio of fragmentation channels varies dramatically. For short spacers length ion pairs with formic anion dissociate through elimination, while bromide through substitution at spacer carbon. When spacer length is long enough to accommodate central anion between two quaternary nitrogens the substitution channel becomes the dominating one for both anions with exception when one of the substituents is hydroxyethyl. Then elimination is the only channel for ion pairs with formate anions, but for bromide anion division between substitution and elimination channels is not much affected. From the trends in channel ration and additional experiment with asymmetric geminis reveal it was concluded that the transition state is probably substantially different for long and short spacer geminis.