Synthesis and cytotoxic activity of acronycine analogues in the benzo[c]pyrano[3,2-h]acridin-7-one and naphtho[1,2-b][1,7] and [1,10]-phenanthrolin-7(14H)-one series

Condensation of 1-bromo-2-naphthalenecarboxylic acid (9) with 7-methoxy-2,2-dimethyl-2H-1-benzopyran-5-ylamine (13) followed by acid-mediated cyclization afforded 6-methoxy-3,3-dimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (15), which was further methylated into 6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (benzo[c]acronycine) (3) and 6,7-dimethoxy-3,3-dimethyl-3H-benzo[c]pyrano[3,2-h]acridine (4). Osmium tetroxide oxidation of 15 gave the (+/-)-cis-diol 16, which afforded the benzopyranoacridine and benzopyranoacridone esters 17-22 upon acylation. Condensation of 9 with suitable aminoquinolines 23-25 afforded the carboxylic naphthylquinolylamines 26-28. Cyclization gave the corresponding naphtho[1,2-b][1,10]-phenanthrolin-7(14H)-ones 29 and 30, and naphtho[1,2-b][1,7]-phenanthrolin-7(14H)-one 31, which were subsequently N-methylated to the desired 14-methylnaphtho[1,2-b][1,10] and [1,7]-phenanthrolinones 6, 7, and 8. Benzo[c]pyrano[3,2-h]acridin-7-one derivatives 3, 16, and 22 displayed cytotoxic activities within the same range of magnitude as acronycine itself, whereas 7-alkoxybenzo[c]pyrano[3,2-h]acridine and 7-acyloxybenzo[c]pyrano[3,2-h]acridine derivatives 4 and 17-21 were less active when tested against L1210 murine leukemia cells in vitro. Naphthophenanthrolinones 6-8 were devoid of significant antiproliferative activity, but compounds 29-31 bearing no substituent on the nitrogen atom at position 14 were more potent.     

SPR imaging for label-free multiplexed analyses of DNA N-glycosylase interactions with damaged DNA duplexes

Base excision repair (BER) is the major mechanism for the correction of damaged nucleobases resulting from the alkylation and oxidation of DNA. The first step in the BER pathway consists of excision of the abnormal base by several specific DNA N-glycosylases. A decrease in BER activity was found to be related to an increased risk of carcinogenesis and aging. To investigate BER activities we set up a new device for DNA repair analysis based on surface plasmon resonance imaging (SPRi). Oligonucleotides bearing an abnormal nucleoside, namely 8-oxo-7,8-dihydro-2'-deoxyguanosine and (5'S)-5',8-cyclopurine-2'-deoxynucleoside, were grafted by a pyrrole electro-copolymerization process on a glass prism coated with a gold layer. The latter label-free DNA sensor chip permits the detection of N-glycosylase/AP-lyase activity as well as the binding of repair proteins to DNA damage without cleavage activity. Thus, the Fapy DNA N-glycosylase (Fpg) protein is shown as expected to bind and then cleave its natural substrate, namely 8-oxo-7,8-dihydro-guanine, together with the resulting abasic site. Using the current SPR imaging-based DNA array we observed an original binding activity of Fpg towards the (5'S)-5',8-cyclodAdenosine residue. These results altogether show that SPR imaging may be used to simultaneously and specifically detect recognition and excision of several damaged DNA nucleobases, and constitutes an interesting technique to screen inhibitors of DNA repair proteins.     

Trifluoromethylated enaminones and their explorative coordination chemistry with Cu(II): synthesis, redox properties and structural characterization of the complexes

The syntheses of three original trifluoromethylated enaminones L1H-L3H, an unexplored type of ligand with possible multiple coordination centres, their redox properties and explorative coordination chemistry with copper(II) are presented. The ability of these ligands to coordinate copper(II) and then to form new mono- and dinuclear complexes is presented and discussed. The consequences of this metal coordination on redox properties are also explored.     

Thermodynamic properties of benzene under shock conditions

We present in this paper a thermodynamic analysis of benzene properties under shock conditions as given by molecular dynamics (MD) simulations. Reactive MD simulations of benzene predict a decomposition threshold corresponding to the flection point on the experimental Hugoniot curve. A polymerlike carbonated structure is observed for pressures above this threshold, but the calculated Hugoniot curve is in disagreement with the experimental one at high pressure. On the contrary, a system consisting of a diamond cluster in hydrogen gas leads to a correct prediction of the pressure on the Hugoniot curves. The central question is then linked to the kinetics of the transition between the polymerlike structure and the diamond cluster.     

The Bogoliubov model of weakly imperfect Bose gas

We present a systematic account of known rigorous results about the Bogoliubov model of weakly imperfect Bose gas (WIBG). This model is a basis of the celebrated Bogoliubov theory of superfluidity, although the physical phenomenon is, of course, more complicated than the model. The theory is based on two Bogoliubov's ansätze: the first truncates the full Hamiltonian of the interacting bosons to produce the WIBG, whereas the second substitutes some operators by c-numbers (the Bogoliubov approximation). After some historical remarks, and physical and mathematical motivations of this Bogoliubov treatment of the WIBG, we turn to revision of the Bogoliubov's ansätze from the point of view of rigorous quantum statistical mechanics. Since the exact calculation of the pressure and the behaviour of the Bose condensate in the WIBG are available, we review these results stressing the difference between them and the Bogliubov theory. One of the main features of the mathematical analysis of the WIBG is that it takes into account quantum fluctuations ignored by the second Bogoliubov ansatz. It is these fluctuations which are responsible for indirect attraction between bosons in the fundamental mode. The latter is the origin of a nonconventional Bose condensation in this mode, which has a dynamical nature. A (generalized) conventional Bose–Einstein condensation appears in the WIBG only in the second stage as a result of the standard mechanism of the total particle density saturation. It coexists with the nonconventional condensation. We give also a review of some models related to the WIBG and to the Bogoliubov theory, where a similar two-stage Bose condensation may take place. They indicate possibilities to go beyond the Bogoliubov theory and the Hamiltonian for the WIBG.     

Etude d'une equation non lineaire d'evolution de type divergentiel

We give a result of existence and uniqueness for a class of nonlinear divergential evolution equations, firstly in the case of a smooth initial data, then in the general case. Under suitable conditions, the dercrease and the regularity of the solution are specified.     

Microscopic Conductivity of Lattice Fermions at Equilibrium. Part II: Interacting Particles

We apply Lieb–Robinson bounds for multi-commutators we recently derived (Bru and de Siqueira Pedra, Lieb–Robinson bounds for multi-commutators and applications to response theory, 2015) to study the (possibly non-linear) response of interacting fermions at thermal equilibrium to perturbations of the external electromagnetic field. This analysis leads to an extension of the results for quasi-free fermions of (Bru et al. Commun Pure Appl Math 68(6):964–1013, 2015; Bru et al. J Math Phys 56:051901-1–051901-51, 2015) to fermion systems on the lattice with short-range interactions. More precisely, we investigate entropy production and charge transport properties of non-autonomous C*-dynamical systems associated with interacting lattice fermions within bounded static potentials and in presence of an electric field that is time and space dependent. We verify the 1st law of thermodynamics for the heat production of the system under consideration. In linear response theory, the latter is related with Ohm and Joule’s laws. These laws are proven here to hold at the microscopic scale, uniformly with respect to the size of the (microscopic) region where the electric field is applied. An important outcome is the extension of the notion of conductivity measures to interacting fermions.     

Synthesis and Reductive Complexation Properties of a Cone-Configurated Tetra[p-(tert-butyl)]calix[4]arene incorporating bipyridyl and pyridine subunits. NMR characterization and crystal structure of its chiral copper(I) complex

The hetero-armed p(tert-butyl)calix[4]arene 1 was synthesized by a stepwise procedure. This ligand presented a very strong complexing behavior towards Cu¹, giving the chiral complex 2 and parent species when reacted with Cu^II salts. High-resolution NMR techniques were employed for the characterization of 2 , demonstrating notably exchange processes between its two enantiomeric forms. The racemic nature of 2 was confirmed by X-ray crystal-structure analysis.