Square-Planar Heteroleptic Complexes of α-Diimine-NiII-Catecholate Type: Intramolecular Ligand-to-Ligand Charge Transfer

Two heteroleptic Ni^II complexes combined the redox-active catecholate and 2,2′- bipyridine ligand platforms were synthesized to observe a photoinduced intramolecular ligand-to-ligand charge transfer (LL’CT, HOMO_catecholate → LUMO_α-diimine). A molecular design of compound [Ni^II(3,6-Cat)(bipy)]∙CH₃CN (1) on the base of bulky 3,6-di-tert-butyl-o-benzoquinone (3,6-DTBQ) was an annelation of the ligand with an electron donor glycol fragment, producing derivative [Ni^II(3,6-Cat^gly)(bipy)]∙CH₂Cl₂ (2), in order to influence the energy of LL’CT transition. A substantial longwave shift of the absorption peak was observed in the UV-Vis-NIR spectra of 2 compared with those in 1. In addition, the studied Ni^II derivatives demonstrated a pronounced negative solvatochromism, which was established using a broad set of solvents. The molecular geometry of both compounds can be ascribed as an insignificantly distorted square-planar type, and the π–π intermolecular stacking of the neighboring α-diimines is realized in a crystal packing. There is a lamellar crystal structure for complex 1, whereas the perpendicular T-motifs with the inter-stacks attractive π–π interactions form the packing of complex 2. The redox-active nature of ligand systems was clearly shown through the electrochemical study: a quasi-reversible one-electron reduction of 2,2′-bipyridine and two reversible successive one-electron oxidative conversations (“catecholate dianion—o-benzosemiquinonato radical anion—neutral o-benzoquinone”) were detected.     

Replacing the Z-phenyl Ring in Tamoxifen® with a para-Connected NCN Pincer-Pt-Cl Grouping by Post-Modification

Post-modification of a series of NCN-pincer platinum(II) complexes [PtX(NCN-R-4)] (NCN = [C₆H₂(CH₂NMe₂)₂-2,6]^–, R = C(O)H, C(O)Me and C(O)Et), X = Cl^– or Br^–) at the para-position using the McMurry reaction was studied. The synthetic route towards two new [PtCl(NCN-R-4)] (R = C(O)Me and C(O)Et) complexes used above is likewise described. The utility and limitations of the McMurry reaction involving these pincer complexes was systematically evaluated. The predicted “homo-coupling” reaction of [PtBr(NCN-C(O)H-4)] led to the unexpected formation of 3,3′,5,5′-tetra[(dimethylamino)methyl]-4,4′-bis(platinum halide)-benzophenone (halide = Br or Cl), referred to hereafter as the bispincer-benzophenone complex 13. This material was further characterized using X-ray crystal structure determination. The applicability of the pincer complexes in the McMurry reaction is shown to open a route towards the synthesis of tamoxifen-type derivatives of which one phenyl ring of Tamoxifen^® itself is replaced by an NCN arylplatinum pincer fragment. The newly synthesized derivatives can be used as potential candidates in anti-cancer drug screening protocols. Two NCN-arylpincer platinum tamoxifen type derivatives, 5 and 6, were successfully synthesized and of 5 the separation of the diastereomeric E-/Z-forms was achieved. Compound 6, which is the pivaloyl protected NCN pincer platinum hydroxy-Tamoxifen^® derivative, was obtained as a mixture of E-/Z-isomers. The new derivatives were further analyzed and characterized with ¹H-, ¹³C{¹H}- and ¹⁹⁵Pt{¹H}-NMR, IR, exact mass MS and elemental analysis.     

Intramolecular tetrazine-acryloyl cycloaddition: chemistry and applications

An unprecedented intramolecular [4 + 2] tetrazine-olefin cycloaddition with α,β-unsaturated substrates was discovered. The reaction produces unique coumarin-dihydropyridazine heterocycles that exhibited strong fluorescence with large Stokes shifts and excellent photo- and pH-stability. This property can be used for reaction analysis. The rate of cycloaddition was found to be solvent dependent and was determined using experimental data with a kinetic modeling software (COPASI) as well as DFT calculations (k₁ = 0.64 ± 0.019 s⁻¹ and 4.1 s⁻¹, respectively). The effects of steric and electronic properties of both the tetrazine and α,β-unsaturated carbonyl on the reaction were studied and followed the known trends characteristic of the intermolecular reaction. Based on these results, we developed a “release-then-click” strategy for the ROS triggered release of methylselenenic acid (MeSeOH) and a fluorescent tracer. This strategy was demonstrated in HeLa cells via fluorescence imaging.

Tetrazines rapidly react with tethered acrylates/acrylamides to produce fused coumarin derivatives. This template can be used in prodrug designs by depleting toxic α,β-unsaturated byproducts while also producing an imaging agent.     

Positron Emission Intensity in the Decay of 86gY for Use in Dosimetry Studies

The β⁺-emitting radionuclide ^86gY (t_1/2 = 14.7 h) forms a matched-pair with the β⁻-emitting therapeutic radionuclide ⁹⁰Y (t_1/2 = 2.7 d) for theranostic application in medicine. This approach demands a precise knowledge of the positron emission probability of the PET nuclide which was until recently rather uncertain for ^86gY. In this work, an ^86gY source of high radionuclidic purity was prepared and a direct measurement of the positron emission intensity per 100 decay of the parent (hereafter “positron emission intensity”) was performed using high-resolution HPGe detector γ-ray spectroscopy. The electron capture intensity was also determined as an additional check by measuring the K_α and K_β X-rays of energies 14.1 and 15.8 keV, respectively, using a low energy HPGe detector. From those measurements, normalized values of 27.2 ± 2.0% for β⁺-emission and 72.8 ± 2.0% for EC were obtained. These results are in excellent agreement with values recently reported in the literature based on a detailed decay scheme study.     

Exploring the 2′-Hydroxy-Chalcone Framework for the Development of Dual Antioxidant and Soybean Lipoxygenase Inhibitory Agents

2′-hydroxy-chalcones are naturally occurring compounds with a wide array of bioactivity. In an effort to delineate the structural features that favor antioxidant and lipoxygenase (LOX) inhibitory activity, the design, synthesis, and bioactivity profile of a series of 2′-hydroxy-chalcones bearing diverse substituents on rings A and B, are presented. Among all the synthesized derivatives, chalcone 4b, bearing two hydroxyl substituents on ring B, was found to possess the best combined activity (82.4% DPPH radical scavenging ability, 82.3% inhibition of lipid peroxidation, and satisfactory LOX inhibition value (IC₅₀ = 70 μM). Chalcone 3c, possessing a methoxymethylene substituent on ring A, and three methoxy groups on ring B, exhibited the most promising LOX inhibitory activity (IC₅₀ = 45 μM). A combination of in silico techniques were utilized in an effort to explore the crucial binding characteristics of the most active compound 3c and its analogue 3b, to LOX. A common H-bond interaction pattern, orienting the hydroxyl and carbonyl groups of the aromatic ring A towards Asp768 and Asn128, respectively, was observed. Regarding the analogue 3c, the bulky (-OMOM) group does not seem to participate in a direct binding, but it induces an orientation capable to form H-bonds between the methoxy groups of the aromatic ring B with Trp130 and Gly247.     

Insertion of Phosphenium Ions into a Bicyclo[1.1.0]Tetraphosphabutane Iron Complex

By reacting [{Cp‴Fe(CO)₂}₂(µ,η^1:1-P₄)] (1) with in situ generated phosphenium ions [Ph₂P][A] ([A]⁻ = [OTf]⁻ = [O₃SCF₃]⁻, [PF₆]⁻), a mixture of two main products of the composition [{Cp‴Fe(CO)₂}₂(µ,η^1:1-P₅(C₆H₅)₂)][PF₆] (2a and 3a) could be identified by extensive ³¹P NMR spectroscopic studies at 193 K. Compound 3a was also characterized by X-ray diffraction analysis, showing the rarely observed bicyclo[2.1.0]pentaphosphapentane unit. At room temperature, the novel compound [{Cp‴Fe}(µ,η^4:1-P₅Ph₂){Cp‴(CO)₂Fe}][PF₆] (4) is formed by decarbonylation. Reacting 1 with in situ generated diphenyl arsenium ions gives short-lived intermediates at 193 K which disproportionate at room temperature into tetraphenyldiarsine and [{Cp‴Fe(CO)₂}₄(µ₄,η^1:1:1:1-P₈)][OTf]₂ (5) containing a tetracyclo[3.3.0.0^2,7.0^3,6]octaphosphaoctane ligand.     

Helical versus Flat Bis-Ferrocenyl End-Capped Peptides: The Influence of the Molecular Skeleton on Redox Properties

Despite the fact that peptide conjugates with a pendant ferrocenyl (Fc) have been widely investigated, bis-ferrocenyl end-capped peptides are rarely synthetized. In this paper, in addition to the full characterization of the Fc-CO-[_L-Dap(Boc)]_n-NH-Fc series, we report a comparison of the three series of bis-ferrocenyl homopeptides synthesized to date, to gain insights into the influence of α-amino isobutyric (Aib), 2,3-diamino propionic (Dap) and C^α,β-didehydroalanine (ΔAla) amino acids on the peptide secondary structure and on the ferrocene redox properties. The results obtained by 2D NMR analysis and X-ray crystal structures, and further supported by electrochemical data, evidence different behaviors depending on the nature of the amino acid; that is, the formation of 3₁₀-helices or fully extended (2.0₅-helix) structures. In these foldamers, the orientation of the carbonyl groups in the peptide helix yields a macrodipole with the positive pole on the N-terminal amino acid and the negative pole on the C-terminal amino acid, so that oxidation of the Fc moieties takes place more or less easily depending on the orientation of the macrodipole moment as the peptide chain grows. Conversely, the fully extended conformation adopted by ΔAla flat peptides neither generates a macrodipole nor affects Fc oxidation. The utilization as electrochemical and optical (Circular Dichroism) probes of the two terminal Fc groups, bound to the same peptide chain, makes it possible to study the end-to-end effects of the positive charges produced by single and double oxidations, and to evidence the presence “exciton-coupled” CD among the two intramolecularly interacting Fc groups of the _L-Dap(Boc) series.     

Novel Sterically Crowded and Conformationally Constrained α-Aminophosphonates with a Near-Neutral pKa as Highly Accurate 31P NMR pH Probes. Application to Subtle pH Gradients Determination in Dictyostelium discoideum Cells

In order to discover new ³¹P NMR markers for probing subtle pH changes (<0.2 pH unit) in biological environments, fifteen new conformationally constrained or sterically hindered α-aminophosphonates derived from diethyl(2-methylpyrrolidin-2-yl)phosphonate were synthesized and tested for their pH reporting and cytotoxic properties in vitro. All compounds showed near-neutral pK_as (ranging 6.28–6.97), chemical shifts not overlapping those of phosphorus metabolites, and spectroscopic sensitivities (i.e., chemical shifts variation Δδ_ab between the acidic and basic forms) ranging from 9.2–10.7 ppm, being fourfold larger than conventional endogenous markers such as inorganic phosphate. X-ray crystallographic studies combined with predictive empirical relationships and ab initio calculations addressed the inductive and stereochemical effects of substituents linked to the protonated amine function. Satisfactory correlations were established between pK_as and both the 2D structure and pyramidalization at phosphorus, showing that steric crowding around the phosphorus is crucial for modulating Δδ_ab. Finally, the hit ³¹P NMR pH probe 1b bearing an unsubstituted 1,3,2-dioxaphosphorinane ring, which is moderately lipophilic, nontoxic on A549 and NHLF cells, and showing pK_a = 6.45 with Δδ_ab = 10.64 ppm, allowed the first clear-cut evidence of trans-sarcolemmal pH gradients in normoxic Dictyostelium discoideum cells with an accuracy of <0.05 pH units.     

Stability and Antiproliferative Activity of Malvidin-Based Non-Oxonium Derivative (Oxovitisin A) Compared with Precursor Anthocyanins and Pyranoanthocyanins

Oxovitisins are a unique group of anthocyanin derivatives with a non-oxonium nature and α-pyranone (lactone) D ring on the structure. In this study, oxovitisin A was synthesized through the micro-oxidative reaction of carboxypyranomalvidin-3-O-glucoside (vitisin A) with water, and its thermostability, pH, and SO₂ color stability were studied compared with its two precursors, malvidin-3-O-glucoside (Mv3glc) and vitisin A, as well as methylpyrano-malvidin-3-O-glucoside (Me-py). Results showed that oxovitisin A exhibited the highest stabilities, which were inseparably related to its noncharged structure and the additional carbonyl group on the D ring. Moreover, the antiproliferative capacity of oxovitisin A was comparatively evaluated against two human gastrointestinal cancer cell lines. Interestingly, oxovitisin A presented the strongest antiproliferative ability on MKN-28 (IC₅₀ = 538.42 ± 50.06 μM) and Caco-2 cells (IC₅₀ = 434.85 ± 11.87 μM) compared with two other pyranoanthocyanins. Therefore, we conclude that oxovitisin A as a highly stable anthocyanin derivative still exhibits a satisfactory antiproliferative ability.     

Pharmacotherapeutics Applications and Chemistry of Chalcone Derivatives

Chalcones have been well examined in the extant literature and demonstrated antibacterial, antifungal, anti-inflammatory, and anticancer properties. A detailed evaluation of the purported health benefits of chalcone and its derivatives, including molecular mechanisms of pharmacological activities, can be further explored. Therefore, this review aimed to describe the main characteristics of chalcone and its derivatives, including their method synthesis and pharmacotherapeutics applications with molecular mechanisms. The presence of the reactive α,β-unsaturated system in the chalcone’s rings showed different potential pharmacological properties, including inhibitory activity on enzymes, anticancer, anti-inflammatory, antibacterial, antifungal, antimalarial, antiprotozoal, and anti-filarial activity. Changing the structure by adding substituent groups to the aromatic ring can increase potency, reduce toxicity, and broaden pharmacological action. This report also summarized the potential health benefits of chalcone derivatives, particularly antimicrobial activity. We found that several chalcone compounds can inhibit diverse targets of antibiotic-resistance development pathways; therefore, they overcome resistance, and bacteria become susceptible to antibacterial compounds. A few chalcone compounds were more active than conventional antibiotics, like vancomycin and tetracycline. On another note, a series of pyran-fused chalcones and trichalcones can block the NF-B signaling complement system implicated in inflammation, and several compounds demonstrated more potent lipoxygenase inhibition than NSAIDs, such as indomethacin. This report integrated discussion from the domains of medicinal chemistry, organic synthesis, and diverse pharmacological applications, particularly for the development of new anti-infective agents that could be a useful reference for pharmaceutical scientists.     

l-Lysine-Based Gelators for the Formation of Oleogels in Four Vegetable Oils

Supramolecular oleogel is a soft material with a three-dimensional structure, formed by the self-assembly of low-molecular-weight gelators in oils; it shows broad application prospects in the food industry, environmental protection, medicine, and other fields. Among all the gelators reported, amino-acid-based compounds have been widely used to form organogels and hydrogels because of their biocompatibility, biodegradation, and non-toxicity. In this study, four N^α, N^ε-diacyl-l-lysine gelators (i.e., N^α, N^ε-dioctanoyl-l-lysine; N^α, N^ε-didecanoyl-l-lysine; N^α, N^ε-dilauroyl-l-lysine; and N^α, N^ε-dimyristoyl-l-lysine) were synthesized and applied to prepare oleogels in four kinds of vegetable oils. Gelation ability is affected not only by the structure of the gelators but also by the composition of the oils. The minimum gel concentration (MGC) increased with the increase in the acyl carbon-chain length of the gelators. The strongest gelation ability was displayed in olive oil for the same gelator. Rheological properties showed that the mechanical strength and thermal stability of the oleogels varied with the carbon-chain length of the gelators and the type of vegetable oil. The microstructure of oleogels is closely related to the carbon-chain length of gelators, regardless of oil type. The highest oil-binding capacity (OBC) was obtained in soybean oil for all four gelators, and N^α, N^ε-dimyristoyl-l-lysine showed the best performance for entrapping oils.     

Synthesis of 4,5-Dihydro-1H-[1,2]dithiolo[3,4-c]quinoline-1-thione Derivatives and Their Application as Protein Kinase Inhibitors

This study represents the design and synthesis of a new set of hybrid and chimeric derivatives of 4,5-dihydro-4,4-dimethyl-1H-[1,2]dithiolo[3,4-c]quinoline-1-thiones, the structure of which the tricyclic fragment linearly bound or/and condensed with another heterocyclic fragment. Using the PASS Online software, among the previously synthesized and new derivatives of 1,2-dithiolo[3,4-c]quinoline-1-thione we identified 12 substances with pleiotropic activity, including chemoprotective and antitumor activity. All the synthesized derivatives were screened for their inhibitory assessment against a number of kinases. Compounds which exhibited prominent inhibition percentage in cells (>85%) were also examined for their inhibitory efficiency on human kinases via ELISA utilizing sorafenib as a reference standard to estimate their IC₅₀ values. It was revealed that compounds 2a, 2b, 2c, and 2q displayed a significant inhibition JAK3 (IC₅₀ = 0.36 μM, 0.38 μM, 0.41 μM, and 0.46 μM, respectively); moreover, compounds 2a and 2b displayed excellent activities against NPM1-ALK (IC₅₀ = 0.54 μM, 0.25 μM, respectively), against cRAF[Y340D][Y341D], compound 2c showed excellent activity, and compound 2q showed weak activity (IC₅₀ = 0.78 μM, 5.34 μM, respectively) (sorafenib IC₅₀ = 0.78 μM, 0.43 μM, 1.95 μM, respectively). Thus, new promising preferred structures for the creation of drugs for the treatment of cancer and other multifactorial diseases in the future have been found.     

Giant Dielectric Properties of W6+-Doped TiO2 Ceramics

The effects of the sintering temperature and doping level concentration on the microstructures, dielectric response, and electrical properties of W⁶⁺-doped TiO₂ (WTO) prepared via a solid-state reaction method were investigated. A highly dense microstructure, pure rutile-TiO₂, and homogenously dispersed dopant elements were observed in all of the ceramic samples. The mean grain size increased as the doping concentration and sintering temperature increased. The presence of oxygen vacancies was studied. A giant dielectric permittivity (ε′ ~ 4 × 10⁴) and low tanδ (~0.04) were obtained in the WTO ceramic sintered at 1500 °C for 5 h. The ε′ response at a low temperature was improved by increasing the doping level concentration. The giant ε′ response in WTO ceramics can be described by the interfacial polarization at the interface between the semiconducting and insulating parts, which was supported by the impedance spectroscopy.     

MiodesinTM Positively Modulates the Immune Response in Endometrial and Vaginal Cells

Endometriosis presents high prevalence and its physiopathology involves hyperactivation of endometrial and vaginal cells, especially by bacteria. The disease has no cure and therapies aiming to inhibit its development are highly desirable. Therefore, this study investigated whether Miodesin^TM (10 µg/mL = IC₈₀; 200 µg/mL = IC₅₀), a natural compound constituted by Uncaria tomentosa, Endopleura uchi, and astaxanthin, could exert anti-inflammatory and anti-proliferative effects against Lipopolysaccharides (LPS) stimulation in endometrial and Candida albicans vaginal cell lines. VK2 E6/E7 (vaginal) and KLE (epithelial) cell lines were stimulated with Candida albicans (1 × 10⁷ to 5 × 10⁷/mL) and LPS (1 μg/mL), respectively. Miodesin^TM inhibited mRNA expression for Nuclear factor kappa B (NF-κB), ciclo-oxigenase 1 (COX-1), and phospholipase A2 (PLA2), beyond the C–C motif chemokine ligand 2 (CCL2), CCL3, and CCL5 in VK2 E6/E7 cells (p < 0.05). In addition, the inhibitory effects of both doses of Miodesin^TM (10 µg/mL and 200 µg/mL) resulted in reduced secretion of interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor α (TNF-α) (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05) by VK2 E6/E7 cells. In the same way, COX-1 Miodesin^TM inhibited LPS-induced hyperactivation of KLE cells, as demonstrated by reduced secretion of IL-1β, IL-6, IL-8, TNF-α (24 h, 48 h, and 72 h) and CCL2, CCL3, and CLL5 (p < 0.05). Furthermore, Miodesin^TM also inhibited mRNA expression and secretion of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor (VEGF), which are key regulators of invasion of endometrial cells. Thus, the study concludes that Miodesin^TM presents beneficial effects in the context of endometriosis, positively affecting the inflammatory and proliferative response.     

Amorphous Polymers’ Foaming and Blends with Organic Foaming-Aid Structured Additives in Supercritical CO2, a Way to Fabricate Porous Polymers from Macro to Nano Porosities in Batch or Continuous Processes

Organic polymers can be made porous via continuous or discontinuous expansion processes in scCO₂. The resulting foams properties are controlled by the interplay of three groups of parameters: (i) Chemical, (ii) physico-chemical, and (iii) technological/process that are explained in this paper. The advantages and drawbacks of continuous (extrusion, injection foaming) or discontinuous (batch foaming) foaming processes in scCO₂, will be discussed in this article; especially for micro or nano cellular polymers. Indeed, a challenge is to reduce both specific mass (e.g., ρ < 100 kg·m⁻³) and cell size (e.g., average pore diameter ϕ_average^pores < 100 nm). Then a particular system where small “objects” (coreshells CS, block copolymer MAM) are perfectly dispersed at a micrometric to nanometric scale in poly(methyl methacrylate) (PMMA) will be presented. Such “additives”, considered as foaming aids, are aimed at “regulating” the foaming and lowering the pore size and/or density of PMMA based foams. Differences between these additives will be shown. Finally, in a PMMA/20 wt% MAM blend, via a quasi one-step batch foaming, a “porous to nonporous” transition is observed in thick samples. A lower limit of pore size (around 50 nm) seems to arise.     

Triphenylantimony(V) Catecholates of the Type (3-RS-4,6-DBCat)SbPh3-Catechol Thioether Derivatives: Structure,Electrochemical Properties,and Antiradical Activity

A new series of triphenylantimony(V) 3-alkylthio/arylthio-substituted 4,6-di-tert-butylcatecholates of the type (3-RS-4,6-DBCat)SbPh₃, where R = n-butyl (1), n-hexyl (2), n-octyl (3), cyclopentyl (4), cyclohexyl (5), benzyl (6), phenyl (7), and naphthyl-2 (8), were synthesized from the corresponding catechol thioethers and Ph₃SbBr₂ in the presence of a base. The crystal structures of 1, 2, 3, and 5 were determined by single-crystal X-ray analysis. The coordination polyhedron of 1–3 is better described as a tetragonal pyramid with a different degree of distortion, while that for 5- was a distorted trigonal bipyramid (τ = 0.014, 0.177, 0.26, 0.56, respectively). Complexes demonstrated different crystal packing of molecules. The electrochemical oxidation of the complexes involved the catecholate group as well as the thioether linker. The introduction of a thioether fragment into the aromatic ring of catechol ligand led to a shift in the potential of the “catechol/o-semiquinone” redox transition to the anodic region, which indicated the electron-withdrawing nature of the RS group. The radical scavenging activity of the complexes was determined in the reaction with DPPH radical.     

Design,Sustainable Synthesis and Biological Evaluation of a Novel Dual α2A/5-HT7 Receptor Antagonist with Antidepressant-Like Properties

The complex pathophysiology of depression, together with the limits of currently available antidepressants, has resulted in the continuous quest for alternative therapeutic strategies. Numerous findings suggest that pharmacological blockade of α₂-adrenoceptor might be beneficial for the treatment of depressive symptoms by increasing both norepinephrine and serotonin levels in certain brain areas. Moreover, the antidepressant properties of 5-HT₇ receptor antagonists have been widely demonstrated in a large set of animal models. Considering the potential therapeutic advantages in targeting both α₂-adrenoceptors and 5-HT₇ receptors, we designed a small series of arylsulfonamide derivatives of (dihydrobenzofuranoxy)ethyl piperidines as dually active ligands. Following green chemistry principles, the designed compounds were synthesized entirely using a sustainable mechanochemical approach. The identified compound 8 behaved as a potent α_2A/5-HT₇ receptor antagonist and displayed moderate-to-high selectivity over α₁-adrenoceptor subtypes and selected serotonin and dopaminergic receptors. Finally, compound 8 improved performance of mice in the forced swim test, displaying similar potency to the reference drug mirtazapine.     

Double-Chain Cationic Surfactants: Swelling,Structure, Phase Transitions and Additive Effects

Double-chain amphiphilic compounds, including surfactants and lipids, have broad significance in applications like personal care and biology. A study on the phase structures and their transitions focusing on dioctadecyldimethylammonium chloride (DODAC), used inter alia in hair conditioners, is presented. The phase behaviour is dominated by two bilayer lamellar phases, L_β and L_α, with “solid” and “melted” alkyl chains, respectively. In particular, the study is focused on the effect of additives of different polarity on the phase transitions and structures. The main techniques used for investigation were differential scanning calorimetry (DSC) and small- and wide-angle X-ray scattering (SAXS and WAXS). From the WAXS reflections, the distance between the alkyl chains in the bilayers was obtained, and from SAXS, the thicknesses of the surfactant and water layers. The L_α phase was found to have a bilayer structure, generally found for most surfactants; a L_β phase made up of bilayers with considerable chain tilting and interdigitation was also identified. Depending mainly on the polarity of the additives, their effects on the phase stabilities and structure vary. Compounds like urea have no significant effect, while fatty acids and fatty alcohols have significant effects, but which are quite different depending on the nonpolar part. In most cases, L_β and L_α phases exist over wide composition ranges; certain additives induce transitions to other phases, which include cubic, reversed hexagonal liquid crystals and bicontinuous liquid phases. For a system containing additives, which induce a significant lowering of the L_β–L_α transition, we identified the possibility of a triggered phase transition via dilution with water.     

Biological Effects on μ-Receptors Affinity and Selectivity of Arylpropenyl Chain Structural Modification on Diazatricyclodecane Derivatives

Opioid analgesics are clinically used to relieve severe pain in acute postoperative and cancer pain, and also in the long term in chronic pain. The analgesic action is mediated by μ-, δ-, and κ-receptors, but currently, with few exceptions for k-agonists, μ-agonists are the only ones used in therapy. Previously synthesized compounds with diazotricyclodecane cores (DTDs) have shown their effectiveness in binding opioid receptors. Fourteen novel diazatricyclodecanes belonging to the 9-propionyl-10-substituted-9,10-diazatricyclo[4.2.1.1^2,5]decane (compounds 20–23, 53, 57 and 59) and 2-propionyl-7-substituted-2,7-diazatricyclo[4.4.0.0^3,8]decane (compounds 24–27, 54, 58 and 60) series, respectively, have been synthesized and their ability to bind to the opioid μ-, δ- and κ-receptors was evaluated. Five of these derivatives, compounds 20, 21, 24, 26 and 53, showed μ-affinity in the nanomolar range with a negligible affinity towards δ- and κ-receptors and high μ-receptor selectivity. The synthesized compounds showed μ-receptor selectivity higher than those of previously reported methylarylcinnamyl analogs.