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Iron deficiency is one of the main causes of chlorosis in plants, which leads to losses in field crops quality and yield. The use of synthetic chelates to prevent or correct iron-deficiency is not satisfactory mainly due to their poor biodegradability. The present work aimed to search suitable microorganisms to produce alternative, environment-friendly iron-chelating agents (siderophores). For this purpose, the performance of five bacteria (Azotobacter vinelandii, Bacillus megaterium, Bacillus subtilis, Pantoea allii and Rhizobium radiobacter) was evaluated, regarding siderophore production kinetics, level of siderophore production (determined by chrome azurol S, CAS method), type of siderophore produced (using Arnow and Csaky’s tests) and iron-chelating capacity at pH 9.0. All bacteria were in stationary phase at 24 h, except A. vinelandii (at 72 h) and produced the maximum siderophore amount (80–140 µmol L−1) between 24 and 48 h, with the exception of A. vinelandii (at 72 h). The analysis of culture filtrates revealed the presence of catechol-type siderophores for B. subtilis and R. radiobacter and hydroxamate-type siderophores for B. megaterium and P. allii. In the case of A. vinelandii, both siderophore-types (catechol and hydroxamates) were detected. The highest iron-chelating capacity, at pH 9.0, was obtained by B. megaterium followed by B. subtilis and A. vinelandii. Therefore, these three bacteria strains are the most promising bacteria for siderophore production and chlorosis correction under alkaline conditions.

A 172Hf/172Lu radionuclide generator system to produce 172Lu for laboratory scale applications in lutetium-based radiochemistry development was established and evaluated. The parent 172Hf radionuclide was produced through 35.2 MeV proton irradiation of natural lutetium metal foil at the Brookhaven Linac Isotope Producer. Four resins were investigated for 172Hf separation from bulk Lu target material: LN resin, ZR resin, in-house synthesized hydroxamate, and methyl-substituted hydroxamate resins, all with comparable performance. Separated 172Hf was consolidated and used to create a ZR resin-based 4.9(3) MBq 172Hf/172Lu generator which was eluted 49 times over two years with no observed breakthrough of 172Hf, and an average elution efficiency of 98(1)%. The eluted 172Lu was used to radiolabel the macrocyclic chelator DOTA with an apparent molar activity of 8(2)x102 kBq/nmol.

This work investigated the hydrophobic flocculation of cassiterite using four alkyl hydroxamic acids with varying carbon chain lengths, i.e., hexyl hydroxamate (C6), octyl hydroxamate (C8), decyl hydroxamate (C10) and dodecyl hydroxamate (C12), as collectors. Microflotation tests were performed to investigate the flotation behaviour of cassiterite in the presence of the four alkyl hydroxamic acids. Focused beam reflectance measurement (FBRM) and a particle video microscope (PVM) were used to analyse and monitor the real-time evolution of the particle size distribution of cassiterite and the images of flocs during flocculation. The extended DLVO theory interaction energies between the cassiterite particles were calculated on the basis of the measured contact angle and the zeta potential of cassiterite to determine the aggregation and dispersion behaviour of the cassiterite particles. The microflotation test results suggested that the floatability of cassiterite improved with the increase in the carbon chain length of hydroxamates. FBRM, PVM images and extended DLVO theory calculation results indicated that when C6 was used as the collector, the cassiterite particles could not form hydrophobic flocs because the total potential energy between them was repulsive. When C8, C10 and C12 were used as collectors, the energy barrier amongst particles decreased with increasing hydroxamate concentration. The lowest concentrations of C8, C10 and C12 that could cause the hydrophobic aggregation of cassiterite were approximately 1 × 10−3, 1 × 10−4 and 2 × 10−5 mol/L, respectively. The aggregation growth rate and apparent floc size increased with an increasing collector concentration. Hydroxamic acid with a longer carbon chain could induce the cassiterite particles to form larger flocs at a lower concentration in a shorter time.

A global strategy, under the coordination of the World Health Organization, is being unfolded to reduce the impact of snakebite envenoming. One of the pillars of this strategy is to ensure safe and effective treatments. The mainstay in the therapy of snakebite envenoming is the administration of animal-derived antivenoms. In addition, new therapeutic options are being explored, including recombinant antibodies and natural and synthetic toxin inhibitors. In this review, snake venom toxins are classified in terms of their abundance and toxicity, and priority actions are being proposed in the search for snake venom metalloproteinase (SVMP), phospholipase A2 (PLA2), three-finger toxin (3FTx), and serine proteinase (SVSP) inhibitors. Natural inhibitors include compounds isolated from plants, animal sera, and mast cells, whereas synthetic inhibitors comprise a wide range of molecules of a variable chemical nature. Some of the most promising inhibitors, especially SVMP and PLA2 inhibitors, have been developed for other diseases and are being repurposed for snakebite envenoming. In addition, the search for drugs aimed at controlling endogenous processes generated in the course of envenoming is being pursued. The present review summarizes some of the most promising developments in this field and discusses issues that need to be considered for the effective translation of this knowledge to improve therapies for tackling snakebite envenoming.

Microorganisms produce siderophores, which are low-molecular-weight iron chelators when iron availability is limited. The present analyzed the role of LNPF1 as multifarious PGPR for improving growth parameters and nutrient content in peanut and soil nutrients. Such multifarious PGPR strains can be used as effective bioinoculants for peanut farming. In this work, rhizosphere bacteria from Zea mays and Arachis hypogaea plants in the Salem area of Tamil Nadu, India, were isolated and tested for biochemical attributes and characteristics that stimulate plant growth, such as the production of hydrogen cyanide, ammonia (6 µg/mL), indole acetic acid (76.35 µg/mL), and solubilizing phosphate (520 µg/mL). The 16S rRNA gene sequences identified the isolate LNPF1 as Pseudomonas fluorescens with a similarity percentage of 99% with Pseudomonas sp. Isolate LNPF1 was evaluated for the production of siderophore. Siderophore-rich supernatant using a Sep Pack C18 column and Amberlite-400 Resin Column ( λ max 264) produced 298 mg/L and 50 mg/L of siderophore, respectively. The characterization of purified siderophore by TLC, HPLC, FTIR, and 2D-NMR analysis identified the compound as desferrioxamine, a hydroxamate siderophore. A pot culture experiment determined the potential of LNPF1 to improve iron and oil content and photosynthetic pigments in Arachis hypogaea L. and improve soil nutrient content. Inoculation of A. hypogea seeds with LNPF1 improved plant growth parameters such as leaf length (60%), shoot length (22%), root length (54.68%), fresh weight (47.28%), dry weight (37%), and number of nuts (66.66) compared to the control (untreated seeds). This inoculation also improved leaf iron content (43.42), short iron content (38.38%), seed iron (46.72%), seed oil (31.68%), carotenoid (64.40%), and total chlorophyll content (98.%) compared to control (untreated seeds). Bacterized seeds showed a substantial increase in nodulation (61.65%) and weight of individual nodules (95.97) vis-à-vis control. The results of the present study indicated that P. fluorescens might be utilized as a potential bioinoculant to improve growth, iron content, oil content, number of nuts and nodules of Arachishypogaea L., and enrich soil nutrients.

In this work, we designed, developed, characterized, and investigated a new chelator and its bifunctional derivative for 89Zr labeling and PET-imaging. In a preliminary study, we synthesized two hexadentate chelators named AAZTHAS and AAZTHAG, based on the seven-membered heterocycle AMPED (6-amino-6-methylperhydro-1,4-diazepine) with the aim to increase the rigidity of the 89Zr complex by using N-methyl-N-(hydroxy)succinamide or N-methyl-N-(hydroxy)glutaramide pendant arms attached to the cyclic structure. N-methylhydroxamate groups are the donor groups chosen to efficiently coordinate 89Zr. After in vitro stability tests, we selected the chelator with longer arms, AAZTHAG, as the best complexing agent for 89Zr presenting a stability of 86.4 ± 5.5% in human serum (HS) for at least 72 h. Small animal PET/CT static scans acquired at different time points (up to 24 h) and ex vivo organ distribution studies were then carried out in healthy nude mice (n = 3) to investigate the stability and biodistribution in vivo of this new 89Zr-based complex. High stability in vivo, with low accumulation of free 89Zr in bones and kidneys, was measured. Furthermore, an activated ester functionalized version of AAZTHAG was synthesized to allow the conjugation with biomolecules such as antibodies. The bifunctional chelator was then conjugated to the human anti-HER2 monoclonal antibody Trastuzumab (Tz) as a proof of principle test of conjugation to biologically active molecules. The final 89Zr labeled compound was characterized via radio-HPLC and SDS-PAGE followed by autoradiography, and its stability in different solutions was assessed for at least 4 days.

Triple negative breast cancer (TNBC) is an urgent as well as huge medical challenge, which is associated with poor prognosis and responsiveness to chemotherapies. Since epigenetic changes are highly implicated in TNBC tumorigenesis and development, inhibitors of histone deacetylases (HDACIs) could represent a promising therapeutic strategy. Although clinical trials involving single HDACIs showed disappointing results against TNBC, recent studies emphasize the high potential impact of HDACIs in controlling TNBC. In addition, encouraging results stem from new compounds designed to obtain isoform selectivity and/or polypharmacological HDAC approach. The present review provides a discussion of the HDACIs pharmacophoric models and of the structural modifications, leading to compounds with a potent activity against TNBC progression.

Background: Actinium-225 ([sup.225]Ac) has gained interest in nuclear medicine for use in targeted alpha therapy (TAT) for the treatment of cancer. However, the number of suitable chelators for the stable complexation of [sup.225]Ac[sup.3+] is limited. The promising physical properties of [sup.225]Ac result in an increased demand for the radioisotope that is not matched by its current supply. To expand the possibilities for the development of [sup.225]Ac-based TAT therapeutics, a new hydroxamate-based chelator, DFO*[sup.12], is described. We report the DFT-guided design of dodecadentate DFO*[sup.12] and an efficient and convenient automated solid-phase synthesis for its preparation. To address the limited availability of [sup.225]Ac, a small-scale [sup.229]Th/[sup.225]Ac generator was constructed in-house to provide [[sup.225]Ac]AcCl[sub.3] for research. Methods: DFT calculations were performed in ORCA 5.0.1 using the BP86 functional with empirical dispersion correction D3 and Becke–Johnson damping (D3BJ). The monomer synthesis over three steps enabled the solid-phase synthesis of DFO*[sup.12]. The small-scale [sup.229]Th/[sup.225]Ac generator was realized by extracting [sup.229]Th from aged [sup.233]U material. Radiolabeling of DFO*[sup.12] with [sup.225]Ac was performed in 1 M TRIS pH 8.5 or 1.5 M NaOAc pH 4.5 for 30 min at 37 °C. Results: DFT calculations directed the design of a dodecadentate chelator. The automated synthesis of the chelator DFO*[sup.12] and the development of a small-scale [sup.229]Th/[sup.225]Ac generator allowed for the radiolabeling of DFO*[sup.12] with [sup.225]Ac quantitatively at 37 °C within 30 min. The complex [[sup.225]Ac]Ac-DFO*[sup.12] indicated good stability in different media for 20 h. Conclusions: The novel hydroxamate-based dodecadentate chelator DFO*[sup.12], together with the developed [sup.229]Th/[sup.225]Ac generator, provide new opportunities for [sup.225]Ac research for future radiopharmaceutical development and applications in TAT.

Histone deacetylases (HDACs) remove acetyl groups from acetylated lysine residues and have a large variety of substrates and interaction partners. Therefore, it is not surprising that HDACs are involved in many diseases. Most inhibitors of zinc-dependent HDACs (HDACis) including approved drugs contain a hydroxamate as a zinc-binding group (ZBG), which is by far the biggest contributor to affinity, while chemical variation of the residual molecule is exploited to create more or less selectivity against HDAC isozymes or other metalloproteins. Hydroxamates have a propensity for nonspecificity and have recently come under considerable suspicion because of potential mutagenicity. Therefore, there are significant concerns when applying hydroxamate-containing compounds as therapeutics in chronic diseases beyond oncology due to unwanted toxic side effects. In the last years, several alternative ZBGs have been developed, which can replace the critical hydroxamate group in HDACis, while preserving high potency. Moreover, these compounds can be developed into highly selective inhibitors. This review aims at providing an overview of the progress in the field of non-hydroxamic HDACis in the time period from 2015 to present. Formally, ZBGs are clustered according to their binding mode and structural similarity to provide qualitative assessments and predictions based on available structural information.

In this study, a strain of Anabaena flos-aquae UTEX 1444 was cultivated in six different concentrations of iron (III). Cultures were extracted with organic solvents and analyzed using our dereplication strategy, based on the combined use of high-resolution tandem mass spectrometry and molecular networking. The analysis showed the presence of the siderophores’ family, named synechobactins, only in the zero iron (III) treatment culture. Seven unknown synechobactin variants were present in the extract, and their structures have been determined by a careful HRMS/MS analysis. This study unveils the capability of Anabaena flos-aquae UTEX 1444 to produce a large array of siderophores and may be a suitable model organism for a sustainable scale-up exploitation of such bioactive molecules, for the bioremediation of contaminated ecosystems, as well as in drug discovery.