Effective degradation of tetracycline by organic-inorganic hybrid materials induced by triethylenediamine.

As an important advanced oxidation technology for environmental purification, photocatalytic degradation has received extensive attention. Designing and synthesizing a catalyst with high-intensity photocatalytic performance is a very challenging subject. Herein, one polydentate cation was synthesized by 1,4-diazabicyclo[2.2.2]octane (DABCO) and 1, 4-bis (bromomethyl) benzene. Inorganic-organic hybrid compounds 1, 2 were synthesized by hydrothermal and room temperature volatilization with inorganic metal salts, namely, {[L1]0.5·[Cu2Br4]0.5}n (1), {[L1]·[Cu2I4]·CH3CN}n (2). Under visible light, compounds 1 and 2 were investigated for their degradation effects on tetracycline (TC) in water. The experimental results showed that compounds 1 and 2 with appropriate concentration of H2O2 had obvious photocatalytic degradation effect on TC. In addition, the influencing factors of photocatalysis such as the amount of adsorbent, the initial concentration of TC and the different pH value were investigated. The photocatalyst exhibits good stability and cyclability.

Cationic Surfactants: Self-Assembly, Structure-Activity Correlation and Their Biological Applications.

The development of biotechnological protocols based on cationic surfactants is a modern trend focusing on the fabrication of antimicrobial and bioimaging agents, supramolecular catalysts, stabilizers of nanoparticles, and especially drug and gene nanocarriers. The main emphasis given to the design of novel ecologically friendly and biocompatible cationic surfactants makes it possible to avoid the drawbacks of nanoformulations preventing their entry to clinical trials. To solve the problem of toxicity various ways are proposed, including the use of mixed composition with nontoxic nonionic surfactants and/or hydrotropic agents, design of amphiphilic compounds bearing natural or cleavable fragments. Essential advantages of cationic surfactants are the structural diversity of their head groups allowing of chemical modification and introduction of desirable moiety to answer the green chemistry criteria. The latter can be exemplified by the design of novel families of ecological friendly cleavable surfactants, with improved biodegradability, amphiphiles with natural fragments, and geminis with low aggregation threshold. Importantly, the development of amphiphilic nanocarriers for drug delivery allows understanding the correlation between the chemical structure of surfactants, their aggregation behavior, and their functional activity. This review focuses on several aspects related to the synthesis of innovative cationic surfactants and their broad biological applications including antimicrobial activity, solubilization of hydrophobic drugs, complexation with DNA, and catalytic effect toward important biochemical reaction.

Biological evaluation of tetracationic compounds based on two 1,4-diazabicyclo[2.2.2]octane moieties connected by different linkers.

A series of 1,4-diazabicyclo[2.2.2]octane derivatives differing by linker moiety was evaluated for activity against several strains of both Gram-positive and Gram-negative bacteria including drug-resistant strains, one strain of fungus and influenza virus A/Puerto Rico/8/34 (H1N1). All compounds exhibited high antibacterial activity against all bacteria except Proteus vulgaris. The minimum inhibitory concentrations (MICs) of compound 1c with an o-phenylenebismethyl linker and compound 1e with a propylene aliphatic linker were found to be low and were comparable or better to the reference drug ciprofloxacin for Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, a time-kill assay was performed to examine the bactericidal kinetics. Compounds 1c and 1e displayed rapid killing effects against St. aureus and Ps. aeruginosa after 2h. Furthermore, compounds 1a-c with aromatic linkers and compound 1e showed the highest antiviral activity.

Modeling 1-Cyano-4-Dimethylaminopyridine Tetrafluoroborate (CDAP) Chemistry to Design Glycoconjugate Vaccines with Desired Structural and Immunological Characteristics.

Glycoconjugation is a well-established technology for vaccine development: linkage of the polysaccharide (PS) antigen to an appropriate carrier protein overcomes the limitations of PS T-independent antigens, making them effective in infants and providing immunological memory. Glycoconjugate vaccines have been successful in reducing the burden of different diseases globally. However, many pathogens still require a vaccine, and many of them display a variety of glycans on their surface that have been proposed as key antigens for the development of high-valency glycoconjugate vaccines. CDAP chemistry represents a generic conjugation strategy that is easily applied to PS with different structures. This chemistry utilizes common groups to a large range of PS and proteins, e.g., hydroxyl groups on the PS and amino groups on the protein. Here, new fast analytical tools to study CDAP reaction have been developed, and reaction conditions for PS activation and conjugation have been extensively investigated. Mathematical models have been built to identify reaction conditions to generate conjugates with wanted characteristics and successfully applied to a large number of bacterial PSs from different pathogens, e.g., Klebsiella pneumoniae, Salmonella Paratyphi A, Salmonella Enteritidis, Salmonella Typhimurium, Shighella sonnei and Shigella flexneri. Furthermore, using Salmonella Paratyphi A O-antigen and CRM197 as models, a design of experiment approach has been used to study the impact of conjugation conditions and conjugate features on immunogenicity in rabbits. The approach used can be rapidly extended to other PSs and accelerate the development of high-valency glycoconjugate vaccines.

Long-Chain Ionic Liquids Based on Monoquaternary DABCO Cations and TFSI Anions: Towards Stable Electrolytes for Electrochemical Capacitors.

The desirable properties of ionic liquids (ILs) enable their use in various branches of chemistry, through a wide range of applications, e. g. as organic electrolytes. In the present study, an efficient two-step method was developed for the synthesis of long-chain ionic liquids with alkyl derivatives of DABCO as cations and bis(trifluoromethane)sulfonimide as anions. ILs obtained with high yields (≥91 %) were solids with melting points that increased with the rise in the number of carbon atoms of the alkyl substituent in the bicyclic cation. The structure of the compounds was confirmed by spectroscopic methods and elemental analysis. All compounds were soluble in the main solvents except water and hexane. The solubility in organic solvents such as acetonitrile allowed the use of synthesized ILs in electrochemical capacitors. Electrochemical tests revealed that the ILs enhanced the conductivity of organic electrolytes. This phenomenon improved the cyclability and reduced the internal resistance of the electrochemical capacitors.

Synthesis, structure-activity relationship and biological evaluation of tetracationic gemini Dabco-surfactants for transdermal liposomal formulations.

In this study, we report the relationship between structure, self-assembly behavior and antimicrobial activity of multicationic gemini surfactants and their successful use as stabilizers of a new liposomal formulation for transdermal drug delivery. New surfactants containing natural moiety 1,4-diazabicyclo[2.2.2]octane with four charges and two hydrophobic chains (n-Dabco-s-Dabco-n, where s = 2, 6, 12 and n = 12, 14, 16, 18) were synthesized. A linear dependence of the CMC decrease, with the increase of the number of carbon atoms in alkyl groups (slope 0.23) was shown. The aggregation numbers of n-Dabco-2-Dabco-n are smaller than 30 and they decrease with increasing alkyl chain length. This is in compliance with the larger surface area per n-Dabco-2-Dabco-n molecule. New liposomal formulations loading Rhodamine B phosphatidylcholine (with mean size about 100 nm and increased zeta potential from -7 ± 2 mV to +55 ± 2 mV) have been successfully stabilized by n-Dabco-s-Dabco-n surfactants. These formulations were designed to improve the bioavailability and skin permeation of loaded compound. The antibacterial activity of Dabco-surfactants was shown to be strongly affected by their structure (alkyl chain length and number of charged nitrogen). 12-Dabco-2-Dabco-12 was the most active (MIC = 0.48, 0.98 and 15.6 µg/mL against S. aureus, B. cereus and E. coli, respectively) without hemolytic activity at 3.1 µg/mL concentration. PC/14-Dabco-2-Dabco-14-liposomes were shown to be the best formulation, with the highest antibacterial activity against Sa (MIC = 7.8 µg‧mL-1) and lowest cytotoxicity (IC50 > 125). The modification of liposomes by Dabco-surfactants stabilizes the membrane of the vesicles, preventing the release of rhodamine B and impairing the penetration of the dye across Strat-M® membrane. Cellular uptake of rhodamine B-loaded PC/12-Dabco-2-Dabco-12-liposomes was also reported. This is the first example of cationic mixed liposomes containing Dabco-surfactants of potential interest for transdermal drug delivery.

Halogen-bonded adduct of 1,2-dibromo-1,1,2,2-tetrafluoroethane and 1,4-diazabicyclo[2.2.2]octane.

Halogen bonding is an intermolecular interaction capable of being used to direct extended structures. Typical halogen-bonding systems involve a noncovalent interaction between a Lewis base, such as an amine, as an acceptor and a halogen atom of a halofluorocarbon as a donor. Vapour-phase diffusion of 1,4-diazabicyclo[2.2.2]octane (DABCO) with 1,2-dibromotetrafluoroethane results in crystals of the 1:1 adduct, C2Br2F4·C6H12N2, which crystallizes as an infinite one-dimensional polymeric structure linked by intermolecular N...Br halogen bonds [2.829 (3) Å], which are 0.57 Šshorter than the sum of the van der Waals radii.

Self-assembling systems based on quaternized derivatives of 1,4-diazabicyclo[2.2.2]octane in nutrient broth as antimicrobial agents and carriers for hydrophobic drugs.

Aggregation properties of mono (mono-CS) and dicationic (di-CS) surfactants, namely quaternised derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO), have been evaluated in water and in nutrient broths of different pH, i.e. in Hottinger broth (рН=7.2) and Sabouraud dextrose broth (рН=5.6). Aggregation capacity of surfactants was shown to be responsible for the solubilization properties of a complex composed of a hydrophobic probe (Sudan I) and a selected drug (quercetin), contributing to the antimicrobial activity of this surfactant system. The effect of N-methyl-d-glucamine (NmDg) additive on the antimicrobial activity of mono-CS, and its aggregation and solubilization parameters, has also been evaluated. A substantial decrease in critical micelle concentration (CMC) of cationic surfactants in nutrient broths (up to 60 times) has been reported. Twofold dilution of monocationic surfactant by NmDg slightly changed the CMC of surfactant; however, it provided a remarkable increase in solubilization capacity (∼by 4 times) and decrease in its toxicity. The data anticipate the potential use of DABCO quaternized derivatives as innovative non-toxic delivery systems for hydrophobic drugs.

Ciliary abnormalities in senescent human fibroblasts impair proliferative capacity.

Somatic cells senesce in culture after a finite number of divisions indefinitely arresting their proliferation. DNA damage and senescence increase the cellular number of centrosomes, the 2 microtubule organizing centers that ensure bipolar mitotic spindles. Centrosomes also provide the basal body from which primary cilia extend to sense and transduce various extracellular signals, notably Hedgehog. Primary cilium formation is facilitated by cellular quiescence a temporary cell cycle exit, but the impact of senescence on cilia is unknown. We found that senescent human fibroblasts have increased frequency and length of primary cilia. Levels of the negative ciliary regulator CP110 were reduced in senescent cells, as were levels of key elements of the Hedgehog pathway. Hedgehog inhibition reduced proliferation in young cells with increased cilium length accompanying cell cycle arrest suggesting a regulatory function for Hedgehog in primary ciliation. Depletion of CP110 in young cell populations increased ciliation frequencies and reduced cell proliferation. These data suggest that primary cilia are potentially novel determinants of the reduced cellular proliferation that initiates senescence.