Efficiency of Dinucleosides as the Backbone to Pre-Organize Multi-Porphyrins and Enhance Their Stability as Sandwich Type Complexes with DABCO.

Flexible linkers such as uridine or 2'-deoxyuridine pre-organize bis-porphyrins in a face-to-face conformation, thus forming stable sandwich complexes with a bidentate base such as 1,4-diazabicyclo[2.2.2]octane (DABCO). Increased stability can be even greater when a dinucleotide linker is used. Such pre-organization increases the association constant by one to two orders of magnitude when compared to the association constant of DABCO with a reference porphyrin. Comparison with rigid tweezers shows a better efficiency of nucleosidic dimers. Thus, the choice of rigid spacers is not the only way to pre-organize bis-porphyrins, and well-chosen nucleosidic linkers offer an interesting option for the synthesis of such devices.

Supramolecular Ionic-Liquid Gels with High Ionic Conductivity.

Supramolecular ionogels were prepared by the gelation of room-temperature ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIm][BF4 ]) with (S,S)-bis(leucinol)oxalamide. Remarkably, the ionic conductivity of solutions and ionogels with low gelator concentrations is higher than that of neat [BMIm][BF4 ]. On the basis of molecular dynamics simulations and quantum mechanical calculations, the origin of this phenomenon is attributed to the higher affinity of gelator molecules towards [BF4 ](-) ions, which reduces the electrostatic attraction between [BMIm](+) and [BF4 ](-) and thus increases their mobility. With increasing gelator concentration, the ionic conductivity decreases due to the formation of a denser gelator matrix, which hinders the pathways for ionic transport. However, even for very dense ionogels, this decrease is less than one order of magnitude relative to neat [BMIm][BF4 ], and thus they can be classified as highly conductive materials with strong potential for application as functional electrolytes.

The formation of CuCl2-specific metallogels of pyridyloxalamide derivatives in alcohols.

Isomeric pyridyloxalamide derivatives 1-3, which differed in the position of the nitrogen atom on the pyridyl ring, showed remarkably different gel-forming aptitudes in the presence of CuCl2 salt in alcohols. Whilst derivatives 1 and 3 formed a soluble complex and a solid precipitate, respectively, ligand 2 generated a remarkably metal- and anion-specific metallogel.

Chiral hexa- and nonamethylene-bridged bis(L-Leu-oxalamide) gelators: the first oxalamide gels containing aggregates with a chiral morphology.

Chiral amino acid- and amino alcohol-oxalamides are well-known as versatile and efficient gelators of various lipophilic and polar organic solvents and water. To further explore the capacity of the amino acid/oxalamide structural fragment as a gelation-generating motif, the dioxalamide dimethyl esters 1(6)Me and 1(9)Me, and dicarboxylic acid 2(6)OH/2(9)OH derivatives containing flexible methylene bridges with odd (9; n=7) and even (6; n=4) numbers of methylene groups were prepared. Their self-assembly motifs and gelation properties were studied by using a number of methods (FTIR, (1)H NMR spectroscopy, CD, TEM, DSC, XRPD, molecular modeling, MMFF94, and DFT). In contrast to the previously studied chiral bis(amino acid or amino alcohol) oxalamide gelators, in which no chiral morphology was ever observed in the gels, the conformationally more flexible 1(6)Me, 1(9)Me, 2(6)OH, and 2(9)OH provide gelators that are capable of forming diverse aggregates of achiral and chiral morphologies, such as helical fibers, twisted tapes, nanotubules, straight fibers, and tapes, in some cases coexisting in the same gel sample. It is shown that the differential scanning calorimetry (DSC)-determined gelation enthalpies could not be correlated with gelator and solvent clogP values. Spectroscopic results show that intermolecular hydrogen-bonding between the oxalamide units provides the major and self-assembly directing intermolecular interaction in the aggregates. Molecular modeling studies reveal that molecular flexibility of gelators due to the presence of the polymethylene bridges gives three conformations (zz, p1, and p2) close in energy, which could form oxalamide hydrogen-bonded layers. The aggregates of the p1 and p2 conformations tend to twist due to steric repulsion between neighboring iBu groups at chiral centers. The X-ray powder diffraction (XRPD) results of 1(6)Me and 1(9)Me, xerogels prove the formation of p1 and p2 gel aggregates, respectively. The latter results explain the formation of gel aggregates with chiral morphology and also the simultaneous presence of aggregates of diverse morphology in the same gel system.

(N-Alkyloxalamido)-Amino Acid Amides as the Superior Thixotropic Phase Selective Gelators of Petrol and Diesel Fuels.

(N-Alkyloxalamido)-amino acid amides 9-12 exhibit excellent gelation capacities toward some lipophilic solvents as well as toward the commercial fuels, petrol and diesel. Gelator 10 exhibits an excellent phase-selective gelation (PSG) ability and also possesses the highest gelation capacity toward petrol and diesel known to date, with minimum gelation concentration (MGC) values (%, w/v) as low as 0.012 and 0.015, respectively. The self-assembly motif of 10 in petrol and toluene gel fibres is determined from xerogel X-ray powder diffraction (XRPD) data via the simulated annealing procedure (SA) implemented in the EXPO2014 program and refined using the Rietveld method. The elucidated motif is strongly supported by the NMR (NOE and variable temperature) study of 10 toluene-d8 gel. It is shown that the triple unidirectional hydrogen bonding between gelator molecules involving oxalamide and carboxamide groups, together with their very low solubility, results in the formation of gel fibres of a very high aspect ratio (d = 10-30 nm, l = 0.6-1.3 µm), resulting in the as-yet unprecedented capacity of gelling commercial fuels. Rheological measurements performed at low concentrations of 10 confirmed the strength of the self-assembled network with the desired thixotropic properties that are advantageous for multiple applications. Instantaneous phase-selective gelation was obtained at room temperature through the addition of the 10 solution to the biphasic mixture of diesel and water in which the carrier solvent was congealed along with the diesel phase. The superior gelling properties and PSG ability of 10 may be used for the development of more efficient marine and surface oil spill recovery and waste water treatment technologies as well as the development of safer fuel storage and transport technologies.

Gamma Radiation- and Ultraviolet-Induced Polymerization of Bis(amino acid)fumaramide Gel Assemblies.

Controlling the polymerization of supramolecular self-assembly through external stimuli holds great potential for the development of responsive soft materials and manipulation at the nanoscale. Vinyl esters of bis(leu or val)fumaramide (1a and 2a) have been found to be gelators of various organic solvents and were applied in this investigation of the influence of organogelators' self-assembly on solid-state polymerization induced by gamma and ultraviolet irradiation. Here, we report our investigation into the influences of self-assemblies of bis(amino acid vinyl ester)fumaramides on gamma-ray- and ultraviolet-induced polymerization. The gelator molecules self-assembled by non-covalent interactions, mainly through hydrogen bonds between the amide group (CONH) and the carboxyl group (COO), thus forming a gel network. NMR and FTIR spectroscopy were used to investigate and characterize supramolecular gels. TEM and SEM microscopy were used to investigate the morphology of gels and polymers. Morphology studies showed that the gels contained a filamentous structure of nanometer dimensions that was exhaustive in a three-dimensional network. The prepared derivatives contained reactive alkyl groups suitable for carrying out the polymerization reaction initiated by gamma or ultraviolet radiation in the supramolecular aggregates of selected gels. It was found that the polymerization reaction occurred only in the network of the gel and was dependent on the structure of aggregates or the proximity and orientation of double bonds in the gel network. Polymers were formed by the gels exposure to gamma and ultraviolet radiation in toluene, and water/DMF gels with transcripts of their gel structure into polymers. The polymeric material was able to immobilize various solvents by swelling. Furthermore, methyl esters of bis(leu and val)fumaramide (1b and 2b) were synthesized; these compounds showed no gelling properties, and the crystal structure of the valine derivative 2b was determined.

Positionally isomeric organic gelators: structure-gelation study, racemic versus enantiomeric gelators, and solvation effects.

Low molecular weight gelator molecules consisting of aliphatic acid, amino acid (phenylglycine), and omega-aminoaliphatic acid units have been designed. By varying the number of methylene units in the aliphatic and omega-aminoaliphatic acid chains, as defined by descriptors m and n, respectively, a series of positionally isomeric gelators having different positions of the peptidic hydrogen-bonding unit within the gelator molecule has been obtained. The gelation properties of the positional isomers have been determined in relation to a defined set of twenty solvents of different structure and polarity and analyzed in terms of gelator versatility (G(ver)) and effectiveness (G(eff)). The results of gelation tests have shown that simple synthetic optimizations of a "lead gelator molecule" by variation of m and n, end-group polarity (carboxylic acid versus sodium carboxylate), and stereochemistry (racemate versus optically pure form) allowed the identification of gelators with tremendously improved versatility (G(ver)) and effectiveness (G(eff)). Dramatic differences in G(eff) values of up to 70 times could be observed between pure racemate/enantiomer pairs of some gelators, which were manifested even in the gelation of very similar solvents such as isomeric xylenes. The combined results of spectroscopic ((1)H NMR, FTIR), electron microscopy (TEM), and X-ray diffraction studies suggest similar organization of the positionally isomeric gelators at the molecular level, comprising parallel beta-sheet hydrogen-bonded primary assemblies that form inversed bilayers at a higher organizational level. Differential scanning calorimetry (DSC) studies of selected enantiomer/racemate gelator pairs and their o- and p-xylene gels revealed the simultaneous presence of different polymorphs in the racemate gels. The increased gelation effectiveness of the racemate compared to that of the single enantiomer is most likely a consequence of its spontaneous resolution into enantiomeric bilayers and their subsequent organization into polymorphic aggregates of different energy. The latter determine the gel fiber thickness and solvent immobilization capacity of the formed gel network.

Oxalyl retro-peptide gelators. Synthesis, gelation properties and stereochemical effects.

In this work we report on gelation properties, self-assembly motifs, chirality effects and morphological characteristics of gels formed by chiral retro-dipeptidic gelators in the form of terminal diacids (1a-5a) and their dimethyl ester (1b-5b) and dicarboxamide (1c-5c) derivatives. Terminal free acid retro-dipeptides (S,S)-bis(LeuLeu) 1a, (S,S)-bis(PhgPhg) 3a and (S,S)-bis(PhePhe) 5a showed moderate to excellent gelation of highly polar water/DMSO and water/DMF solvent mixtures. Retro-peptides incorporating different amino acids (S,S)-(LeuPhg) 2a and (S,S)-(PhgLeu) 4a showed no or very weak gelation. Different gelation effectiveness was found for racemic and single enantiomer gelators. The heterochiral (S,R)-1c diastereoisomer is capable of immobilizing up to 10 and 4 times larger volumes of dichloromethane/DMSO and toluene/DMSO solvent mixtures compared to homochiral (S,S)-1c. Based on the results of (1)H NMR, FTIR, CD investigations, molecular modeling and XRPD studies of diasteroisomeric diesters (S,S)-1b/(S,R)-1b and diacids (S,S)-1b/(S,R)-1a, a basic packing model in their gel aggregates is proposed. The intermolecular hydrogen bonding between extended gelator molecules utilizing both, the oxalamide and peptidic units and layered organization were identified as the most likely motifs appearing in the gel aggregates. Molecular modeling studies of (S,S)-1a/(S,R)-1a and (S,S)-1b/(S,R)-1b diasteroisomeric pairs revealed a decisive stereochemical influence yielding distinctly different low energy conformations: those of (S,R)-diastereoisomers with lipophilic i-Bu groups and polar carboxylic acid or ester groups located on the opposite sides of the oxalamide plane resembling bola amphiphilic structures and those of (S,S)-diasteroisomers possessing the same groups located at both sides of the oxalamide plane. Such conformational characteristics were found to strongly influence both, gelator effectiveness and morphological characteristics of gel aggregates.

Biological properties of 4-methyl-2,7-diamino-5,10-diphenyl-4,9-diazapyrenium hydrogensulfate (ADAP).

OBJECTIVE: 4-Methyl-2,7-diamino-5,10-diphenyl-4,9-diazapyrenium hydrogensulfate (ADAP) is a potential antitumor compound because of its DNA and RNA intercalating ability. In this study, cellular uptake, intracellular distribution as well as mechanism of action, antitumor activity in vitro and toxicity in vivo of ADAP were investigated. METHODS: Based on the fluorescence properties of ADAP, its entry and distribution into live cells were analyzed by fluorescence microscopy. The in vitro antiproliferative activity was determined using MTT test. For screening of topoisomerase II-targeted effects of ADAP, the cell-free assay and immunoband depletion assay were used. Expression of the genes c-mos, c-N-ras, c-Ki-ras, c-H-ras, p53 and caspase 3 in Caco-2 cells treated with ADAP was examined by RT-PCR. Toxicity in vivo was determined using C3HHf/Bu Zgr/Hr mice treated by single or multiple doses of ADAP at a concentration of 25 mg/kg. RESULTS: ADAP in microM concentrations entered into MIAPaCa-2 cell's cytoplasm in 5 min and into nuclei in 60 min after administration. Intracellular distribution of ADAP depended on the period of treatment time. ADAP (0.1-100 microM) strongly inhibited the growth of both mouse (FsaR, SCCVII) and human tumor cells (HeLa, Caco-2, HT-29, MIAPaCa-2, HBL, HEp-2, SW620, MCF-7) compared to its weak cytotoxicity on controls and normal cells (WI38). Results of both topoisomerase II assays showed that ADAP is not a topoisomerase II poison. Expression of investigated genes was dependent on the incubation time, except for p53 and c-H-ras. Morphological changes in tissues and organs of mice were not observed. Results of patohistological analysis have been confirmed by hematological and clinical-chemical analysis of blood of treated and non-treated animals. CONCLUSION: ADAP is a strongly bioactive compound with antitumor potential in vitro. The antitumor potential in vivo remains to be identified.

The Metal Effect on Self-Assembling of Oxalamide Gelators Explored by Mass Spectrometry and DFT Calculations.

Gels formed by self-assembly of small organic molecules are of wide interest as dynamic soft materials with numerous possible applications, especially in terms of nanotechnology for functional and responsive biomaterials, biosensors, and nanowires. Four bis-oxalamides were chosen to show if electrospray ionization mass spectrometry (ESI-MS) could be used as a prediction of a good gelator and also to shed light on the gelation processes. By inspecting the gelation of several solvent, we showed that bis(amino acid)oxalamide 1 proved to be the most efficient, also being able of forming the largest observable assemblies in the gas phase. The formation of singly charged assemblies holding from one up to six monomer units is the outcome of the strong intermolecular H-bonds, particularly among terminal carboxyl groups. The variation of solvents from polar aprotic towards polar protic did not have any significant effects on the size of the assemblies. The addition of a salt such as NaOAc or Mg(OAc)2, depending on the concentration, altered the assembling. Computational analysis at the DFT level aided in the interpretation of the observed trends and revealed that individual gelator molecules spontaneously assemble to higher aggregates, but the presence of the Na+ cation disrupts any gelator organization since it becomes significantly more favorable for gelator molecules to bind Na+ cations up to the 3:1 ratio than to self-assemble, being fully in line with experimental observations reported here. Graphical Abstract ᅟ.

Fluoride-responsive organogelator based on oxalamide-derived anthraquinone.

Anthraquinone derived oxalamide gelator 1 forms with aromatic solvents and alcohols very stable gels which selectively respond to the presence of fluoride anion by colour change and/or gel-to-sol transition.

Specific sensing of poly G by the aluminum-salophen complex.

The Al(III)-salophen complex 1 exhibited strong spectroscopic changes specifically upon addition of polyG and GpG, while double stranded DNA and RNA, and single stranded polyA, polyU and polyC induced negligible spectral changes of 1. Titrations with mono-nucleotides yielded no spectroscopic changes, revealing that there must be at least two consecutive guanines in single stranded oligonucleotide structure for a measurable spectroscopic change of 1. Preliminary results show that 1 has moderate antiproliferative effect on a number of human tumour cell lines.

Interactions of quercetin and its lanthane complex with double stranded DNA/RNA and single stranded RNA: spectrophotometric sensing of poly G.

Spectrophotometric titrations revealed that stability of the quercetin/double stranded (ds) DNA or double stranded (ds) RNA non-covalent complexes is significantly higher compared to the quercetin/ss-RNA complexes. This observation can easily be correlated with the significantly larger aromatic surface of base pairs compared to single nucleobases, and it is in good agreement with other experimental data pointing toward intercalative binding mode of quercetin. Fluorescence increase of quercetin induced by ds-RNA is significantly stronger than observed for ds-DNA, offering usage of quercetin as the ds-RNA selective fluorescent probe. Also, addition of poly G yielded more than order of magnitude stronger changes in UV/visible and fluorescence spectrum of quercetin compared to the changes upon addition of poly A and poly U revealing possible usage of quercetin as a powerful spectroscopic probe for poly G sequences. Stability and stoichiometry of lanthane(III)/quercetin complexes in physiologically relevant aqueous media was determined. The interactions of (LaQ)(3+) with double stranded DNA and RNA were significantly different compared to the free quercetin, revealing increase of complex stability and thus significant impact of La(III) in binding of (LaQ)(3+) to polynucleotides. Similar results were observed for interactions of (LaQ)(3+) with single stranded RNA.

Novel cyano- and N-isopropylamidino-substituted derivatives of benzo[b]thiophene-2-carboxanilides and benzo[b]thieno[2,3-c]quinolones: synthesis, photochemical synthesis, crystal structure determination, and antitumor evaluation. 2.

Derivatives of 3-chlorobenzo[b]thiophene-2-carboxanilides and their "cyclic" analogues benzo[b]thieno[2,3-c]quinolones were synthesized. Spectroscopic study of the interactions of some representatives of "cyclic" derivatives and their "acyclic" precursors with ds-DNA/RNA supported strong intercalative binding of the former and weak nonintercalative binding of the latter group of compounds. All tested compounds showed a certain antiproliferative effect on a series of human tumor cells and on a normal cell line. Among the compounds, those with one amidino-substituent have shown the best effect. The most active benzo[b]thieno[2,3-c]quinolones induced apparent S and G2/M arrests of the cell cycle, which resulted in apoptosis. These results strongly suggest that the compounds may act as topoisimerase "poisons", which is in good agreement with their intercalative mode of binding to ds-DNA/RNA, in contrast to the studied "acyclic"group of derivatives. 6a and 6d showed the best selectivity by inhibiting the growth of tumor cells but not of normal fibroblasts.

Cholesterol-based gelators.

This chapter is intended to provide a comprehensive overview of the chemistry and molecular structures of cholesterol-based low molecular mass organogelators and to describe the underlying principles that are responsible for self-assembly and, in turn, organogel formation within this important class of systems. In particular, the properties of the resulting organogels are discussed in terms of the relationship between the designed structure of the gelator, the nature of the gelled organic fluid component, the influence of molecular interactions (π-π stacking, Van der Waals, hydrogen bonding, …), and chirality. Emphasis is given to the remarkably high synthetic tunability of the cholesterol-based organogelators, which enable access to a range of functional gels. The prospects for future applications of cholesteryl molecular gels will be illustrated and discussed at the end of the chapter.

Systematic design of amide- and urea-type gelators with tailored properties.

The formation of gels by structurally highly diverse low molecular weight organic molecules is paradigmatically a supramolecular phenomenon. It is based on the self-assembly of certain organic molecules and involves highly specific noncovalent intermolecular interactions, in particular those inducing predominantly unidirectional aggregation. In this chapter, the design of low molecular weight gelators that incorporate single or multiple amide units as intermolecular hydrogen-bonding functionalities and methods of their preparation are given. Many efficient gelators of organic solvents and water could be prepared by the structural combination of amidic, carbamate, urea, or oxalamide groups and long aliphatic chains or aromatic groups with a large surface. The numerous potential applications in slow drug-delivery systems, the fabrication of templated materials, and in sensing devices are also discussed.

Recognition of homo-polynucleotides containing adenine by a phenanthridinium bis-uracil conjugate in aqueous media.

Among novel bis-nucleobase-phenanthridinium conjugates bis-uracil analogue stabilized significantly more effective poly-dA-poly-dT and poly-AH(+)-poly-AH(+) than adenine analogue and reference compound . For the alternating poly-dAdT-poly-dAdT however, the binding preference is lost, pointing to the importance of specific interactions of uracils of with homopolynucleotides containing consecutive adenines.

Gels with exceptional thermal stability formed by bis(amino acid) oxalamide gelators and solvents of low polarity.

Some bis (amino acid) oxalamide gelators form common thermo-reversible gels with various organic solvents but also gels of exceptional thermal stability with some solvents of medium and low polarity; the latter gels can be heated up to 50 degrees C higher temperatures than the bp of the solvent without apparent gel-to-sol transition.

11-Aminoundecanoic acid: a versatile unit for the generation of low molecular weight gelators for water and organic solvents.

The use of 11-aminoundecanoic acid as a synthetic building-block allows the systematic preparation of (oligo)amide organogelators-including chiral ones-which display remarkable gelation properties in organic solvents and water.