Factors influencing structural heat-induced structural relaxation of dissolved organic matter

Physical and chemical structure affect properties of dissolved organic matter (DOM). Recent observations revealed that heating and cooling cycles at higher temperature amplitude lead to a change in DOM physical conformation assumingly followed by a slow structural relaxation. In this study, changes at lower temperature amplitudes and their relation to DOM composition were investigated using simultaneous measurements of density and ultrasonic velocity in order to evaluate the adiabatic compressibility, which is sensitive indicator of DOM structural microelasticity. Six fulvic acids (FAs) having various origins were analyzed at concentrations of 0.12, 0.6 and 1.2 g L−1 and at different temperature amplitudes. First, we validated that the used technique is sensitive to distinguish conclusively the structural changes upon heating and cooling of DOM with heating/cooling amplitude of ± 3 °C and higher. This amplitude was then applied to observe the relationship between change in adiabatic compressibility and chemical composition of FA. No correlation was observed with elemental composition and aromatic structures. Positive correlations were observed with content of alkyl moieties, carboxylic and carbonyl carbons and biological activity. Based on literature data, it was concluded that alkyl moieties undergo (re)crystalization during thermal fluctuation and their structural relaxation back is very slow (if occurs). The polar moieties form a flexible hydrogel responding to thermal fluctuation by moderate dissolution and re-aggregation. Negative correlation was observed in relation to the amount of peptide and O-alkyl systems, which can be attributed to very fast structural relaxation of proteinaceous materials, i.e. their larger content leads to lower difference between original and heat-induced compressibility. Last, the increase of the heating/cooling amplitude from ± 3 to ± 15 °C resulted in an increase of the change of the adiabatic compressibility and in the extension of the relaxation time needed for DOM structure to return to the equilibrium. We conclude that this increase is caused by the increase in inner energy, and DOM conformation can reach a cascade of energy minima, which may influence DOM reactivity and biodegradability

The solution structure of a 3'-phenazinium (Pzn) tethered DNA-RNA duplex with a dangling adenosine: r(5'G-AUUGAA3'):d(5'TCAATC3'-Pzn).

The 3'-Pzn group tethered to an oligo-DNA stabilizes a DNA-RNA hybrid duplex structure by 13 degrees C compared to the natural counterpart. This report constitutes the first full study of the conformational features of a hybrid DNA-RNA duplex, which has been possible because of the unique stabilization of this rather small duplex by the tethered 3'-Pzn moiety (Tm approximately 40 degrees C from NMR). In this study, a total of 252 inter- and intra-strand torsional and distance constraints along with the full NOE relaxation matrix, taking into account the exchange process of imino and amino protons with water, have been used. The 3'-Pzn-promoted stabilization of the DNA-RNA hybrid duplex results in detailed local conformational characteristics such as the torsion angles of the backbone and sugar moieties that are close to the features of the other natural DNA-RNA hybrids (i.e. sugars of the RNA strand are 3'-endo, but the sugars of the DNA strand are intermediate between A- and B-forms of DNA, 72 degrees < P < 180 degrees; note however, that the sugars of our DNA strand have a C1-exo conformation: 131 degrees < P < 154 degrees). This study suggests that 3'-Pzn-tethered smaller oligo-DNA should serve the same purpose as a larger oligo-DNA as a antisense inhibitor of the viral mRNA. Additionally, these types of tethered oligos have been found to be relatively more resistant to the cellular nuclease. Moreover, they are taken up quite readily through the cellular membrane (14) compared to the natural counterparts

Design and Synthesis of Pyrano[3,2-b]indolones Showing Antimycobacterial Activity

Latent Mycobacterium tuberculosis infection presents one of the largest challenges for tuberculosis control and novel antimycobacterial drug development. A series of pyrano[3,2-b]indolone-based compounds was designed and synthesized via an original eight-step scheme. The synthesized compounds were evaluated for their in vitro activity against M. tuberculosis strains H37Rv and streptomycin-starved 18b (SS18b), representing models for replicating and nonreplicating mycobacteria, respectively. Compound 10a exhibited good activity with MIC99 values of 0.3 and 0.4 μg/mL against H37Rv and SS18b, respectively, as well as low toxicity, acceptable intracellular activity, and satisfactory metabolic stability and was selected as the lead compound for further studies. An analysis of 10a-resistant M. bovis mutants disclosed a cross-resistance with pretomanid and altered relative amounts of different forms of cofactor F420 in these strains. Complementation experiments showed that F420-dependent glucose-6-phosphate dehydrogenase and the synthesis of mature F420 were important for 10a activity. Overall these studies revealed 10a to be a prodrug that is activated by an unknown F420-dependent enzyme in mycobacteria