Hydroxamic Group Research Articles

A lead-free flotation process for enriching wolframite with H2O2 and dithiocarbamate-hydroxamic acid

The green and eco-friendly flotation process to enrich wolframite under lead-free pulp is an attractive issue, which is promising to be broken through an innovative oxidation flotation approach with H2O2 and N-[(3-hydroxyamino)-propoxy]-N-hexyl dithiocarbamate (HAHD). The flotation results indicated that in comparison to the traditional technology with lead ion pre-activation and benzohydroxamic acid (BHA) collection, the new approach with H2O2 oxidation and HAHD flotation dramatically promoted the floatability of wolframite. In situ AFM showed that H2O2 eroded wolframite surface and effectively enhanced the adsorption of HAHD. XPS proved that H2O2 treatment increased the proportion of Fe(Ⅲ) on/in wolframite interface. Interestingly, the dithiocarbamate group (-C(=S)S−) of HAHD was confirmed to be oxidized to the thiuram structure of –C(=S)–S–S-(S=)C-, i.e., HAHD was oxidized to (HAHD)2 on wolframite surface. Thus, the two hydroxamate groups of (HAHD)2 combined with two Fe(Ⅲ) sites, leaving the thiuram structure and two hexyl groups outward for attaching air bubbles. The “H” configuration of (HAHD)2 adsorption model intensified the hydrophobicity of wolframite, which returned the high flotation recovery. Therefore, the lead-free flotation of wolframite was achieved.

Preparation of cinnamic hydroxamic acid collector and study on flotation characteristics and mechanism of scheelite

In this paper, using methyl cinnamate as raw material, the new cinnamic hydroxamic acid collector (CIHA) was synthesized by the hydroxylamine method. The collector performance of hydroxamic acid was investigated for scheelite and gangue calcite, and the flotation separation test of scheelite and calcite was carried out with CIHA as the collector. The interaction mechanism between hydroxamic acid and scheelite minerals has also been investigated through zeta potential, Fourier transform infrared spectroscopy (FTIR) experiments, X-ray photoelectron spectroscopy (XPS) experiments, and density functional theory (DFT) calculation. The single mineral flotation test and artificially mixed ore showed that CIHA had an excellent collection effect and selectivity. Zeta potential, FTIR, and XPS showed that CIHA was adsorbed on the scheelite surface by strong chemical adsorption. The active group of CIHA was analyzed through quantum chemical calculation. It was speculated that CO and NO bonds could synthesize a five-membered chelated hydroxamic acid group with Ca element chelate on scheelite surface, changing hydrophobicity and making it more likely to emerge from the pulp.

Amide group enhanced self‐assembly and adsorption of thioether‐containing hydroxamic acid on cassiterite surface

AbstractModified surfactants can regulate their adsorption at the target surface and are essential for various separation applications such as froth flotation. Thioether‐containing hydroxamic acid (BTHA) is an excellent oxidized‐ore collector with poor dispersibility. Herein, acylamino, which possesses the ability to improve the surfactants' self‐assembly and dispersion, was introduced to synthesize N‐[6‐(hydroxyamino)‐6‐oxohexyl] benzylthioacetamide (BTAHA); thus, applying it to cassiterite flotation. Surface tension, adsorption capacity, in situ AFM, and surface energy results reveal BTAHA displays strong bubble stability and readily adsorbs onto the mineral's surface, promoting hydrophobic flotation. BTAHA is an effective cassiterite collector and has good separation effects on cassiterite against calcite. It can form Van der Waals forces and five‐membered hydroxamate‐(O,O)‐Sn rings with Sn atoms on cassiterite surfaces via thioether and hydroxamate groups. Meanwhile, the presence of intermolecular hydrogen bond between the amide groups facilitates the self‐assembly of the collectors on the cassiterite surface, and has broad industrial application prospects in various separation processes.

Design, synthesis, and biological activity studies on benzimidazole derivatives targeting myeloperoxidase

Myeloperoxidase (MPO) plays a key role in human antimicrobial system by oxidizing vital molecules of microorganisms in phagolysosomes through produced hypochlorous acid (HOCl). However, MPO can be released outside the phagocyte and produces reactive intermediates leading to tissue damage. MPO, as a local mediator of tissue damage, has been associated with inflammatory diseases such as renal injury, multiple sclerosis, cardiovascular and neurodegenerative diseases. Therefore, the enzyme currently draws attention as a potential therapeutic target. In this study, isomeric 1,3-dihydro-2H-benzo[d]imidazole-2-thione derivatives having amide, hydrazide and hydroxamic acid groups either on nitrogen or on sulphur atom were designed and their inhibitory activity was determined on chlorination and peroxidation cycles of MPO. Among the compounds, 2-(2-thioxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)acetohydrazide(C19) was found as the most active inhibitor on both cycles.

C-Diazeniumdiolate Graminine in the Siderophore Gramibactin Is Photoreactive and Originates from Arginine.

Siderophores are synthesized by microbes to facilitate iron acquisition required for growth. Catecholate, hydroxamate, and α-hydroxycarboxylate groups comprise well-established ligands coordinating Fe(III) in siderophores. Recently, a C-type diazeniumdiolate ligand in the newly identified amino acid graminine (Gra) was found in the siderophore gramibactin (Gbt) produced by Paraburkholderia graminis DSM 17151. The N-N bond in the diazeniumdiolate is a distinguishing feature of Gra, yet the origin and reactivity of this C-type diazeniumdiolate group has remained elusive until now. Here, we identify l-arginine as the direct precursor to l-Gra through the isotopic labeling of l-Arg, l-ornithine, and l-citrulline. Furthermore, these isotopic labeling studies establish that the N-N bond in Gra must be formed between the Nδ and Nω of the guanidinium group in l-Arg. We also show the diazeniumdiolate groups in apo-Gbt are photoreactive, with loss of nitric oxide (NO) and H+ from each d-Gra yielding E/Z oxime isomers in the photoproduct. With the loss of Gbt's ability to chelate Fe(III) upon exposure to UV light, our results hint at this siderophore playing a larger ecological role. Not only are NO and oximes important in plant biology for communication and defense, but so too are NO-releasing compounds and oximes attractive in medicinal applications.

Deferoxamine-Based Materials and Sensors for Fe(III) Detection

Deferoxamine (DFO) is a siderophore widely studied for its ability to bind iron(III) strongly. Thanks to its versatility, it is suitable for several clinical and analytical applications, from the recognized iron(III) chelation therapy to the most recent applications in sensing. The presence of three hydroxamic functional groups enables Deferoxamine to form stable complexes with iron(III) and other divalent and trivalent metal ions. Moreover, the terminal amino group in the DFO molecule, not involved in metal ion complexation, allows modification or functionalization of solid phases, nanoobjects, biopolymers, electrodes and optical devices. This review summarizes and discusses deferoxamine-based applications for the chelation and recognition of Fe(III).

Functionalization of gum arabic derivatives for catalytic neutralization of organophosphates

Aiming sustainable catalysts to neutralize toxic organophosphates, we functionalized gum arabic derivatives -commercial and industrial waste- with hydroxamate groups via covalent bonds. The polymeric catalysts promote the effective degradation of organophosphates with selectivity and recycling. Half-lifetimes of over 20 years (without catalysts) can be reduced to 30 min in the presence of the catalysts. Hence, biocompatible and waste-derived polymeric materials are promising scaffolds for biocatalysts for promoting chemical security.

A guanidinium group is an effective mimic of the tertiary carbocation formed by isopentenyl diphosphate isomerase

Type I isopentenyl diphosphate isomerase is a metal-dependent enzyme that generates a tertiary carbocation intermediate during catalysis. This study describes an inhibitor (2-guanidinoethyl(dihydroxyphosphorylmethyl)phosphinate) of the isomerase that bears a guanidinium as a carbocation mimic and a phosphinylphosphonate as a non-hydrolyzable metal binding functionality. Inhibition kinetics show that the compound acts in a competitive manner with a Ki value of 129 nM (KM,IPP/Ki = 27). An analogous inhibitor bearing a tertiary ammonium as the carbocation mimic was 50-fold less potent, suggesting that the planar guanidinium is a more effective carbocation mimic. Inhibitors bearing an acylated methanesulfonamide or a hydroxamate group in place of the pyrophosphate inhibited the enzyme at millimolar concentrations indicating that the isomerase is highly specific for binding to the diphosphate portion of the intermediate.

Flotation separation of fluorite from calcite using bis hydroxamic acid collector

The efficient separation of fluorite and calcite is a challenging task in the field of mineral processing because of their similar chemical and physical properties. In this research, octylamino-bis-(butanohydroxamic acid) (OBHA) was introduced as collector into a flotation system comprising fluorite and calcite, and the separation of fluorite and calcite was realized in the absence of any depressants. ζ potential, FTIR, XPS measurements and DFT calculations were performed to investigate the mechanism for the selective adsorption of OBHA. The results indicate that the hydroxamic acid group of OBHA account for the adsorption process, and the adsorption of the hydroxamic acid group on fluorite was much stronger than that on calcite surface.

Development of Hydroxamic Acid Compounds for Inhibition of Metallo-β-Lactamase from Bacillus anthracis.

The emergence of resistant bacteria takes place, endangering the effectiveness of antibiotics. A reason for antibiotic resistance is the presence of lactamases that catalyze the hydrolysis of β-lactam antibiotics. An inhibitor of serine-β-lactamases such as clavulanic acid binds to the active site of the enzymes, thus solving the resistance problem. A pressing issue, however, is that the reaction mechanism of metallo-β-lactamases (MBLs) hydrolyzing β-lactam antibiotics differs from that of serine-β-lactamases due to the existence of zinc ions in the active site of MBLs. Thus, the development of potential inhibitors for MBLs remains urgent. Here, the ability to inhibit MBL from Bacillus anthracis (Bla2) was investigated in silico and in vitro using compounds possessing two hydroxamate functional groups such as 3-chloro-N-hydroxy-4-(7-(hydroxyamino)-7-oxoheptyl)benzamide (Compound 4) and N-hydroxy-4-(7-(hydroxyamino)-7-oxoheptyl)-3-methoxybenzamide (Compound 6). In silico docking and molecular dynamics simulations revealed that both Compounds 4 and 6 were coordinated with zinc ions in the active site, suggesting that the hydroxamate group attached to the aromatic ring of the compound plays a crucial role in the coordination to the zinc ions. In vitro kinetic analysis demonstrated that the mode of inhibitions for Compounds 4 and 6 were a competitive inhibition with Ki values of 6.4 ± 1.7 and 4.7 ± 1.4 kcal/mol, respectively. The agreement between in silico and in vitro investigations indicates that compounds containing dihyroxamate moieties may offer a new avenue to overcome antibiotic resistance to bacteria.

Enhanced flotation of Pb(II)-activated wolframite using a novel collector

ABSTRACT The flotation enrichment of fine-particle wolframite played a crucial role in production of strategic key metal tungsten. In this paper, N-[(3-hydroxyamino)-propoxy]-N-hexyl dithiocarbamate (HAHD) was designed to strengthen the flotation recovery of wolframite. The in situ AFM images clearly exhibited that the pre-activation of wolframite with Pb2+ ions significantly enhanced the self-assemble and aggregation of HAHD on its surface, and its surface hydrophobicity and floatability dramatically improved. The FTIR and XPS results recommended a chemisorption of HAHD to the Pb(II)-activated wolframite, and in the surface HAHD-Pb(II) complexes, both dithiocarbamate and hydroxamate groups chelated Pb(II) to deliver the four-membered and five-membered ring configurations. The double-site adsorption rendered a closed loop anchor of HAHD on the Pb(II)-activated wolframite surface, which essentially weakened the hydration of OH- ions toward Pb2+, Fe2+ or Mn2+ ions in/on wolframite interface. In addition, the hexyl group exhibits a strong hydrophobization, and the dithiocarbamate displays a selective affinity against alkaline earth metal minerals. These encouraged HAHD to be a strong-power and selective collector for wolframite versus calcite at its low dose.

SKLB-14b, a novel oral microtubule-destabilizing agent based on hydroxamic acid with potent anti-tumor and anti-multidrug resistance activities

A hydroxamic acid based microtubule-destabilizing agent (MDA) SKLB-14b was discovered in this study, which was derived from shortening the linker length of the HDAC6 and microtubule dual-target inhibitor SKLB-23bb. SKLB-14b exhibited low nanomolar IC50 values on a wide spectrum of human cancer cell lines including both sensitive and multidrug-resistant cell lines. Surprisingly, its anti-proliferative activity relied on the presence of the hydroxamic acid group but lost inhibitory activity against HDACs. SKLB-14b bound to the colchicine site of tubulin and could inhibit tubulin polymerization. It exhibited good metabolic stability in liver microsomes, no inhibitory effect on CYP450 isoenzymes and high oral bioavailability. In vivo experiments revealed that SKLB-14b was potent in both sensitive (A2780S, HCT116) and resistant (A2780/T) xenograft mice models. Furthermore, in the patient-derived tumor xenograft (PDX) models of osimertinib resistant non-small cell lung cancer (NSCLC), 50 mg/kg of SKLB-14b administered every twodays inhibited tumor growth by 70.6% without obvious toxicity, better than the 59.7% inhibition rate of paclitaxel. Mechanistically, we found that SKLB-14b exerted anti-tumor and anti-multidrug resistance effects in vitro and in vivo through cell cycle arrest and pro-apoptotic activities, as well as vascular disrupting activities. Therefore, we discovered that SKLB-14b, as a novel MDA based on hydroxamic acid, could serve as a potential drug candidate for cancer therapy which deserves further investigation.

Strengthening flotation enrichment of Pb(Ⅱ)-activated scheelite with N-[(3-hydroxyamino)-propoxy]-N-hexyl dithiocarbamate

To improve the flotation recovery of tungsten minerals was of an urgent issue. In this paper, N-[(3-hydroxyamino)-propoxy]-N-hexyl dithiocarbamate (HAHD) was designed as a powerful collector to enrich and separate scheelite particles. In comparison to benzohydroxamic acid (BHA), HAHD dramatically promoted the floatability of the Pb(Ⅱ)-activated scheelite. Meanwhile, HAHD exhibited a competent selectivity for flotation separation of scheelite from calcite. The findings of zeta potential, contact angle, FTIR, UV and XPS deduced that both HAHD’s dithiocarbamate and hydroxamate groups were of the reactive centers to the Pb(Ⅱ)-activated scheelite where the surface HAHD-Pb(Ⅱ) complex was generated. The introduction of the dithiocarbamate group had a limited influence on HAHD’s flotation affinity towards calcite, while strengthened HAHD aggregation on to the Pb(Ⅱ)-activated scheelite surface, the floatability difference between scheelite and calcite significantly increased. Moreover, the “h-shape” adsorption mode and hexyl group of HAHD possessed a stronger hydrophobization towards scheelite than the single-site adsorption and benzene ring of BHA, returning a higher flotation recovery of scheelite particles.

Catalytic Activity of Fibrous Complexites

The ecological situation in the world requires the solution of environmental problems associated with the processes of wastewater treatment, hydrogen sulfide pollution of various industrial facilities in order to remove such harmful impurities. The unpleasant odor that appears in industrial and adjacent waste processing areas is a constant concern for the protection of the environment. To solve these problems, it is advisable to use selective sorbents - complex. The introduction of metal ions into complex fibers due to the formation of a coordinated bond between the groups of the metal and the polymer ligand gives high molecular weight complex compounds. The operational and selective properties of the materials based on high-molecular-weight complex compounds can be determined by the type of metal ion introduced into macromolecules, the nature of the polymer chain, and thermodynamic stability. By changing the action of the above factors, complexites can be synthesized for use as highly selective catalysts for various chemical processes. The paper presents data on the catalytic activity of fibers with Cu2+, Co2+, Ni2+ ions with complexing fibers containing carboxyl, amidoxime, hydroxamic groups, using the example of the decomposition of hydrogen peroxide and oxidation of H2S, Na2S. An inhibitory effect on the oxidation of fiber functional groups in the pH range 5.5 - 12.5 was revealed. The operational and selective properties of materials based on complexites can be determined by the type of metal ion introduced into the macromolecules, by the nature of the polymer chain. By changing the action of the above factors, complexites can be synthesized to be used as highly selective catalysts for various chemical processes. It was found that the catalytic activity of the complex depends on pH, the stereochemistry of the coordination centers in the fiber matrix and significantly exceeds the activity of model low-molecular-weight complex compounds.

Metastatic spread inhibition of cancer cells through stimuli-sensitive HPMA copolymer-bound actinonin nanomedicines

The unresolved task of modern medicine is to prevent metastatic spread during and after the treatment of primary tumors. Here, the design, controlled synthesis, in-depth physicochemical and biological characteristics of a novel panel of well-defined water-soluble copolymer conjugates bearing actinonin intended for advanced drug delivery and inhibition of metastatic spread are described. Three different synthetic approaches were employed to covalently attach actinonin to the N-(2-hydroxypropyl)methacrylamide copolymers to control the release of actinonin to its pharmacologically active form. Actinonin was attached to the polymers via hydroxamate group suppressing its activity during the delivery, with the activity restored after its release in the primary tumors or metastatic foci. Importantly, developed nanosystems with favorable drug release kinetics inhibited the metastatic spread of cancer cells from primary 4T1 tumors into the lungs as well as invasion of B16F10 melanoma cells from circulation into the lungs at the dosage without any sign of toxicity.

Preparation of cinnamon hydroxamic acid and its flotation characteristics and mechanism to fine-grained wolframite

A new collector—cinnamon hydroxamic acid (CIHA)—was synthesized from methyl cinnamate using the hydroxyamine method. The results of single-mineral flotation and artificially mixed-mineral flotation indicated that CIHA had good collection performance and selectivity. Adsorption-capacity test results indicated that the CIHA collector adsorbed wolframite and quartz, and the adsorption intensity of wolframite was higher than that of quartz. The adsorption mechanism was investigated via zeta-potential analysis, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The results indicated that CIHA interacted with Mn on the wolframite surface via Pb2+ activation to form a surface Mn–O–Pb2+ complex, which formed a new Fe–O bond with Fe. Hydroxamic acid may have formed a five-element chelated hydroxamic group with the metal on the wolframite surface. The hydrophobicity of the wolframite surface was improved, making the wolframite more easily attach to bubbles and be more easily carried to the pulp surface.

Behavior and Mechanism of a Novel Hydrophobic Collector in the Flotation of Bastnaesite

In order to improve the recovery of rare earth elements, finding a collector with a strong selectivity ability had become the focus of research. In this paper, phenylpropyl hydroxamic acid (PHA) was used as a new hydrophobic surfactant collector for the separation of bastnaesite from calcite, and salicylic hydroxamic acid (SHA) was used as a reference collector. The results of a single mineral flotation test with SHA show that the reagent has good collection performance and selectivity. In addition, Zeta potential measurements and FTIR analysis show that PHA is adsorbed on the surface of bastnaesite by chemical adsorption, and the surface state of bastnaesite changes after PHA treatment. By XPS analysis, PHA interacts with Ce, and forms a Ce–O bond with Ce. It is speculated that the hydroxamic acid forms a five-element-chelated hydroxamic group with Ce on bastnaesite surface, so as to improve the hydrophobicity of bastnaesite, and make bastnaesite float more easily out of the pulp. According to DFT calculation, PHA has better adsorption capacity and stronger hydrophobicity than SHA, and shows superior electronic group capacity and chemical reactions that promote its flotation performance.

Synthesis and evaluation of Diaza-Crown Ether-Backboned chelator containing hydroxamate groups for Zr-89 chelation chemistry

Zirconium-89 (89Zr) has been explored for molecularly targeted positron emission tomography (PET) imaging of various diseases. We synthesized and evaluated a novel chelator (DA-18C6-BHA) for 89Zr. The new chelator is structured on a macrocyclic backbone (1,10-diaza-18-crown-6) and contains hydroxamates as acyclic donor groups. The new chelator ((DA-18C6-BHA) was rapidly labeled with 89Zr under mild conditions. The 89Zr-labeled DA-18C6-BHA complex remained stable in human serum and apotransferrin for 7 days. When challenged with excess EDTA solution, 89Zr-labeled DA-18C6-BHA was shown to hold 89Zr without losing considerable radioactivity to EDTA. The 89Zr-labeled DA-18C6-BHA complex displayed high complex stability in normal mice as evidenced by low bone uptake.

Design, synthesis, and biological evaluation of histone deacetylase inhibitor with novel salicylamide zinc binding group.

Introduction:Histone deacetylases (HDACs) have emerged as important therapeutic targets for various diseases, such as cancer and neurological disorders. Although a majority of HDAC inhibitors use hydroxamic acids as zinc binding groups, hydroxamic acid zinc-binding groups suffer from poor bioavailability and nonspecific metal-binding properties, necessitating a new zinc-binding group. Salicylic acid and its derivatives, well-known for their therapeutic value, have also been reported to chelate zinc ions in a bidentate fashion. This drew our attention towards replacing hydroxamic acid with salicylamide as a zinc-binding group.Methods:In this study, for the first time, compound 5 possessing a novel salicylamide zinc-binding group was synthesized and evaluated biologically for its ability to inhibit various HDAC isoforms and induce acetylation upon α-tubulin and histone H3 among MDA-MB-231 cells.Results:Compound 5 exhibits selective inhibition against class I HDAC isoforms (HDAC1, 2, and 3) over class II and IV HDAC isoforms (HDAC4, 6, and 11). The exposure of MDA-MB-231 cells to compound 5 efficiently induced the acetylation of more histone H3 than α-tubulin, suggesting that compound 5 is a class I selective HDAC inhibitor. Moreover, the molecular docking study indicated that the salicylamide zinc-binding group of compound 5 coordinates the active zinc ion of class I HDAC2 in a bidentate fashion.Conclusion:Overall, salicylamide represents a novel zinc-binding group for the development of class I selective HDAC inhibitors.Graphical abstract:

Carrier-Free Deferoxamine Nanoparticles against Iron Overload in Brain

Carrier-Free Deferoxamine Nanoparticles against Iron Overload in Brain