Please cite this article as: S. Jeremic, L. Djokic, V. Ajdačić, et al., Production of bacterial nanocellulose (BNC) and its application as a solid support in transition metal catalysed cross-coupling reactions, International Journal of Biological Macromolecules, https://doi. AbstractBacterial nanocellulose (BNC) emerged as an attractive advanced biomaterial that provides desirable properties such as high strength, lightweight, tailorable surface chemistry, hydrophilicity, and biodegradability.BNC was successfully obtained from a wide range of carbon sources including sugars derived from grass biomass using Komagataeibacter medellinensis ID13488 strain with yields up to 6 g L -1 in static fermentation. Produced BNC was utilized in straightforward catalyst preparation as a solid support for two different transition metals, palladium and copper with metal loading of 20 and 3 weight %, respectively. Sustainable catalysts were applied in the synthesis of valuable fine chemicals, such as biphenyl-4-amine and 4'fluorobiphenyl-4-amine, used in drug discovery, perfumes and dye industries with excellent product yields of up to 99%. Pd/BNC catalyst was reused 4 times and applied in two consecutive reactions, Suzuki-Miyaura cross-coupling reaction followed by hydrogenation of nitro to amino group while Cu/BNC catalyst was examined in Chan-Lam coupling reaction.Overall, the environmentally benign process of obtaining nanocellulose from biomass, followed by its utilisation as a solid support in metal-catalysed reactions and its recovery has been described. These findings reveal that BNC is a good support material, and it can be used as a support for different catalytic systems.

A series of new thiophene-based guanylhydrazones (iminoguanidines) were synthesized in high yields using a straightforward two-step procedure. The antifungal activity of compounds was evaluated against a wide range of medicaly important fungal strains including yeasts, molds, and dermatophytes in comparison to clinically used drug voriconazole. Cytotoxic properties of compounds were also determined using human lung fibroblast cell line and hemolysis assay. All guanylhydrazones showed significant activity against broad spectrum of clinically important species of Candida spp., Aspergillus fumigatus, Fusarium oxysporum, Microsporum canis and Trichophyton mentagrophytes, which was in some cases comparable or better than activity of voriconazole. More importantly, compounds 10, 11, 13, 14, 18 and 21 exhibited excellent activity against voriconazole-resistant Candida albicans CA5 with very low minimal inhibitory concentration (MIC) values <2 μg mL(-1). Derivative 14, bearing bromine on the phenyl ring, was the most effective compound with MICs ranging from 0.25 to 6.25 μg mL(-1). However, bis-guanylhydrazone 18 showed better selectivity in terms of therapeutic index values. In vivo embryotoxicity on zebrafish (Danio rerio) showed improved toxicity profile of 11, 14 and 18 in comparison to that of voriconazole. Most guanylhydrazones also inhibited C. albicans yeast to hyphal transition, essential for its biofilm formation, while 11 and 18 were able to disperse preformed Candida biofilms. All guanylhydrazones showed the equal potential to interact with genomic DNA of C. albicans in vitro, thus indicating a possible mechanism of their action, as well as possible mechanism of observed cytotoxic effects. Tested compounds did not have significant hemolytic effect and caused low liposome leakage, which excluded the cell membrane as a primary target. On the basis of computational docking experiments using both human and cytochrome P450 from Candida it was concluded that the most active guanylhydrazones had minimal structural prerequisites to interact with the cytochrome P450 14α-demethylase (CYP51). Promising guanylhydrazone derivatives also showed satisfactory pharmacokinetic profile based on molecular calculations.

Recently the reactions H 2 (7r"~,y)2n and H 2 (w, p)2n were investigated with the aim of determining the neutron-neutron l S 0 scattering length, a nn . The preferred value for a nn extracted from the first reaction is 1 ' 2 -17 F, unfortunately with an uncertainty of about 5 F. Several investigations 3 " 5 of the second reaction gave values around -22 F. While the theoretical analysis of the reaction H 2 (7T~,y)2« can be performed with an accuracy of ±1 F, 8 the reactions with more than two nucleons in the final state are considerably more difficult for interpretation.In a reaction a+A-~b +n + n the spectrum of the particle b reflects the neutron-neutron final-state interaction. However, distortive effects arise from at least two sources 7 :(i) Interaction between b and the system 2w. It is reasonable to expect that this depends upon the type of the particle b and on the relative b-2n energy.(ii) The interference between the n-n and the n-b resonances 8 and the interference between resonant and nonresonant processes. 9 The study of the reaction H 3 (n,d)2n offers another possibility 4 to extract a nn . The comparison of the reaction E 2 (n f p)2n and E B (n,d)2n allows one also to investigate the influence of the various distortive effects.In order to determine kinematically such a reaction one has to measure five parameters. The measurement of the energy of the charged particle at 0° at a fixed incident energy is, thus, an incomplete measurement, and only that region of the spectrum which corresponds to the strong final-state interaction of the two neutrons is liable to meaningful interpretation.The deuteron spectra from the reaction H 3 (n, d)2n at E n = 14.4 MeV were measured with different detecting systems. The targets used were (1) a solid Cu-Ti-H 3 target containing 0.3 mg of H 3 and 10% of He 3 ; (2) two gas targets, one containing 0.1 mg and the other 1.3 mg of H 3 , with the He 3 content less than 0.4%. The charged particles were detected with a semiconductor counter telescope 10 in conjunction with multidimensional analyzers. 11 The telescope consisted of two thin AE counters and an E counter depleted to detect 11.5-MeV protons.Two pulses (from the A£ 2 and E counters) were analyzed by a lOOxlOO-channel analyzer. The resulting three-dimensional graphs gave proton, deuteron, and triton &E 2 -vs-E spectra simultaneously. 12 In a set of measurements three pulses (from the AE lf &E 29 and E counters) were analyzed by a lOOxlOOxlOO-channel analyzer. All those events for which AE X and AE 2 pulses did not satisfy specific criteria were rejected. 13

Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone- and guanidine-containing molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C. parapsilosis) minimal inhibitory concentrations (MICs) of bis-guanylhydrazones were between 2 and 15.6 μg/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitro DNA interaction, circular dichroism, and molecular docking analysis showed the great ability of these compounds to bind fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane, and activation of metacaspases were shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the accumulation of reactive oxygen species in C. albicans, as only twofold MIC and higher concentrations of BG3 caused depolarization of mitochondrial membrane which was accompanied by the decrease of the activity of fungal mitochondrial dehydrogenases, while the activity of oxidative stress response enzymes glutathione reductase and catalase was not significantly affected. BG3 showed synergistic activity with amphotericin B with a fractional inhibitory concentration index of 0.5. It also exerted low cytotoxicity and the ability to inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans SC5314. With further developments, BG3 may further progress in the antifungal pipeline as a DNA-targeting agent.

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