Hydroxamic Acid Ligands Research Articles

Assembly of zinc metallacrowns with an α-amino hydroxamic acid ligand

In the assembly of metallacrowns for molecular recognition, luminescence, and molecular magnetism applications, substituting the ring ion can have profound effects on the structure, stability, and physical properties of the inorganic macrocycle. The assembly of Zn(II) metallacrowns with an α-amino hydroxamic acid ligand (pheHA) was investigated to compare the assembly behavior with the well studied metallacrowns containing Cu(II) and Ni(II). Electrospray ionization mass spectrometry reveals that the benchmark species Zn5(pheHA)42+ and LnZn5(pheHA)53+ assemble in pyridine, which is consistent with the behavior of Cu(II) and Ni(II). A LnZn4(pheHA)43+ species is also observed in a 1:1 DMF-pyridine mixture. An unprecedented La(III)[16-MCZn(II),pheHA,HpheHA-6]5+ complex was crystallographically characterized that possesses unusual C2 symmetry. These results provide insights into the design of functional metallacrowns through ring ion substitution.

Synthesis, structural characterization, VHPO mimicking peroxidative bromination and DNA nuclease activity of oxovanadium(v) complexes

The two novel oxovanadium(V) complexes [VO(PyDC)(BHA)] (1) [PyDC = pyridine-2,6-dicarboxylate, BHA = benzohydroxamate] and [VO(PyDC)(BPHA)] (2) [BPHA = benzophenyl hydroxamate] were synthesized by successive addition of a methanolic solution of H2PyDC and the corresponding hydroxamic acid ligand to the aqueous solution of ammonium metavanadate (NH4VO3). The hydroxamic acid ligands were characterized by elemental analysis, IR, UV-vis and NMR studies whereas the complexes were characterized by IR, UV-vis, CHN, molar conductance, magnetic moment, mass and NMR spectroscopic methods. The structures of the complexes were determined by single crystal X-ray crystallography. The structures of both complexes reveal that vanadium(V) has distorted octahedral geometry. The bromoperoxidase activities of these complexes have been demonstrated through the activation of C-H bonds of phenol, o-cresol and p-cresol. The catalytic products have been characterized by GC-MS analysis which shows that good conversions have been achieved. So far as the catalytic efficiency of the complexes are concerned complex 2 is found to be superior to complex 1. Both the complexes were tested for DNA nuclease activity with pUC19 plasmid DNA. The results show that both of them exhibited nuclease activity against pUC19 circular plasmid DNA. The complexes produced both nicked coils and linear forms. In this case also it is observed that complex 2 shows better nuclease activity than complex 1.

An enthalpic basis of additivity in biphenyl hydroxamic acid ligands for stromelysin-1

Fragment based drug discovery remains a successful tool for pharmaceutical lead discovery. Although based upon the principle of thermodynamic additivity, the underlying thermodynamic basis is poorly understood. A thermodynamic additivity analysis was performed using stromelysin-1 and a series of biphenyl hydroxamate ligands identified through fragment additivity. Our studies suggest that, in this instance, additivity arises from enthalpic effects, while interaction entropies are unfavorable; this thermodynamic behavior is masked by proton transfer. Evaluation of the changes in constant pressure heat capacities during binding suggest that solvent exclusion from the binding site does not account for the dramatic affinity enhancements observed.

Theoretical Study of Asymmetric Transfer Hydrogenation of Ketones Catalyzed by Amino Acid‐Derived Rhodium Complexes

AbstractDensity functional theory calculations are employed to study the asymmetric transfer hydrogenation of ketones catalyzed by rhodium–arene complexes containing hydroxamic acid‐functionalized amino acid ligands. Firstly, the ligand–metal binding is investigated and it is shown that both the N,N and O,O binding modes Are viable. For each of these, the full free energy profile for the transfer hydrogenation is calculated according to the outer‐sphere reaction mechanism. Three factors are demonstrated to influence the stereoselectivity of the process, namely the energy difference between the metal–ligand binding modes, the energy difference between the intermediate hydrogenated catalyst, and the existence of a stabilizing CH–π interaction between the Cp* ligand of the catalyst and the phenyl moiety of the substrate. Theoretical reproduction of the selectivity of a slightly modified ligand that is shown experimentally to yield the opposite enantioselectivity corroborates these results. Finally, a technical observation made is that inclusion of dispersion interactions (using the B3LYP‐D2 correction or the M06 functional) proved to be very important for reproducing the enantioselectivity.

Influencing the Size and Anion Selectivity of Dimeric Ln3+[15-Metallacrown-5] Compartments through Systematic Variation of the Host Side Chains and Central Metal

Dimeric Ln(3+)[15-metallacrown-5] compartments selectively recognize carboxylates through guest binding to host metal ions and intermolecular interactions with the phenyl side chains. A systematic study is presented on how the size, selectivity, and number of encapsulated guests in the dimeric containers is influenced by the Ln(3+)[15-metallacrown(Cu(II))-5] ligand side chain and central metal. Compartments of varying heights were assembled from metallacrowns with S-phenylglycine hydroxamic acid (pgHA), S-phenylalanine hydroxamic acid (pheHA), and S-homophenylalanine hydroxamic acid (hpheHA) ligands. Guests that were examined include the fully deprotonated forms of terephthalic acid, isonicotinic acid, and bithiophene dicarboxylic acid (btDC). X-ray crystallography reveals that the side-chain length constrains the maximum and minimum length guest that can be encapsulated in the compartment. Compartments with heights ranging from 9.7 to 15.2 Å are formed with different phenyl side chains that complex 4.3-9.2 Å long guests. Up to five guests are accommodated in Ln(3+)[15-metallacrown(Cu(II))-5] compartments depending on steric effects from the host side chains. The nine-coordinate La(3+) central metal promotes the encapsulation of multiple guests, while the eight-coordinate Gd(3+) typically binds only one dicarboxylate. Electrospray ionization mass spectrometry reveals that the dimerization phenomenon occurs beyond the solid state, suggesting that these containers can be utilized in solid-state and solution applications.

Cobalt complexes with tripodal ligands: implications for the design of drug chaperones

Extensive research is currently being conducted into metal complexes that can selectively deliver cytotoxins to hypoxic regions in tumours. The development of pharmacologically suitable agents requires an understanding of appropriate ligand-metal systems for chaperoning cytotoxins. In this study, cobalt complexes with tripodal tren (tris-(2-aminoethyl)amine) and tpa (tris-(2-pyridylmethyl)amine) ligands were prepared with ancillary hydroxamic acid, β-diketone and catechol ligands and several parameters, including: pK(a), reduction potential and cytotoxicity were investigated. Fluorescence studies demonstrated that only tpa complexes with β-diketones showed any reduction by ascorbate in situ and similarly, cellular cytotoxicity results demonstrated that ligation to cobalt masked the cytotoxicity of the ancillary groups in all complexes except the tpa diketone derivative [Co(naac)tpa](ClO(4))(2) (naac = 1-methyl-3-(2-naphthyl)propane-1,3-dione). Additionally, it was shown that the hydroxamic acid complexes could be isolated in both the hydroxamate and hydroximate form and the pK(a) values (5.3-8.5) reveal that the reversible protonation/deprotonation of the complexes occurs at physiologically relevant pHs. These results have clear implications for the future design of prodrugs using cobalt moieties as chaperones, providing a basis for the design of cobalt complexes that are both more readily reduced and more readily taken up by cells in hypoxic and acidic environments.

Synthesis and characterization of poly(hydroxamic acid)–poly(amidoxime) chelating ligands from polymer‐grafted acacia cellulose

AbstractGraft copolymerization of methyl acrylate (MA) and acrylonitrile (AN) onto acacia cellulose was carried out using free radical initiating process in which ceric ammonium nitrate (CAN) was used as an initiator. The optimum grafting yield was determined by the certain amount of acacia cellulose (AGU), mineral acid (H2SO4), CAN, MA, and AN at 0.062, 0.120, 0.016, 0.397, and 0.550 mol L−1, respectively. The poly(methyl acrylate‐co‐acrylonitrile)‐grafted acacia cellulose was obtained at 55°C after 2‐h stirring, and purified acrylic polymer‐grafted cellulose was characterized by FTIR and TG analysis. Therein, the ester and nitrile functional groups of the grafted copolymers were reacted with hydroxylamine solution for conversion into the hydroxamic acid and amidoxime ligands. The chelating behavior of the prepared ligands toward some metal ions was investigated using batch technique. The metal ions sorption capacities of the ligands were pH dependent, and the sorption capacity toward the metal ions was in the following order: Zn2+ > Fe3+ > Cr3+ > Cu2+ > Ni2+. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Stability of Metal Chelates of Some Hydroxamic Acid Ligands

The binary–ligand complexes formed between acetohydroxamic acid (Aha) and benzohydroxamic acid (Bha) ligands and selected transition metals (Sc(III), Y(III), and La(III)) were investigated potentiometrically in aqueous solution at (25 ± 0.1) °C and I = 0.10 M NaCl to determine the protonation constants of the free ligands and stability constants of the binary complexes. The complexation model for each metal–ligand system was established from the potentiometric data using the software program BEST. The concentration distributions of the various metal–ligand complexes formed in solution were also evaluated. The complex stability was found to follow the trend Sc(III) > Y(III) > La(III) based on the ionic radius of the metal ions.

Corrigendum: Asymmetric Transfer Hydrogenation of Ketones Catalyzed by Amino Acid Derived Rhodium Complexes: On the Origin of Enantioselectivity and Enantioswitchability

In the Full Paper by Adolfsson and co-workers, the structure of the valine-derived ligand 4 d is unfortunately incorrect. During further studies on amino acid derived hydroxamic acid ligands, the authors have found that the hydrogenation method used for generating compound 4 d, from its N-carbobenzyloxy (Cbz)-protected analogue, also cleaved the NO bond in the hydroxamic acid functionality. Therefore, the authors would like to withdraw all data concerning ligand 4 d, (i.e., the catalytic results presented in entries 7 and 8 in Table 2, and the preparation methods given in the Supporting Information). It should be added that other results and conclusions presented in the paper, are not affected by this error. To illustrate the latter, the rhodium-catalyzed transfer hydrogenation of acetophenone in 2-propanol using the L-phenylalanine-derived ligand 4 l, and conditions given in footnote [a] of Table 2, resulted in a 13 % conversion and 21 % enantiomeric excess (ee) (R) of 1-phenylethanol. When the same reaction was performed in the presence of LiCl (5 mol %), 64 % conversion and 34 % ee (R) of the secondary alcohol was obtained. The authors sincerely apologize for this error and any inconvenience it may have caused.1

Structural diversity of organotin(IV) complexes self-assembled from hydroxamic acid and mono- or dialkyltin salts

Three hydroxamic acid ligands (HL 1 = acetohydroxamic acid; HL 2 = benzohydroxamic acid; HL 3 = N–phenylbenzohydroxamic acid), have been used to synthesize series of mono- or dialkyltin(IV) complexes, which include (i) the carboxyl acid hybrid five-coordinated dialkyltin complexes (C 4H 9) 2SnL 1L 4 ( 1), [(CH 3) 2SnL 2L 5]·0.5C 6H 6 ( 2), (HL 4 = acetic acid; HL 5 = benzoic acid); (ii) the six-coordinated mono- n-butyltin complexes (C 4H 9)SnL 1·Cl 2·H 2O ( 3), (C 4H 9)SnL 2·Cl 2·H 2O ( 4), [(C 4H 9)SnL 3·Cl 2·H 2O]·H 2O ( 5), [(C 4H 9Sn) 2(L 3) 2·Cl 2·(OCH 3) 2] ( 6); and (iii) the alkali metal-mingled seven-coordinated mono- n-butyltin complexes [(C 4H 9Sn) 3L 2Na] +·Cl −·(CH 3CH 2) 2O ( 7), [(C 4H 9Sn) 3L 2K] +·Cl −·CH 2Cl 2 ( 8). All complexes were characterized by elemental analyses, IR, 1H, 13C, 119Sn NMR and X-ray single crystal diffraction. In these complexes, hydroxamic acids present bidentate coordination modes with the carbonyl O atom and the hydroxyl O atom binding to tin center. In complexes 1– 6, each tin atom is coordinated by one hydroxamic acid ligand. However, in complexes 7 and 8, tin atom is surrounded by three hydroxamic acid ligands, and all hydroxyl O atoms of the ligands also bind to the alkali metal center (Na or K). This kind of organotin(IV) framework containing one alkali metal is found for the first time. Furthermore, the supramolecular structures of 1, 3, 4 and 6 have been found to consist of 1D linear molecular chains formed by intermolecular N–H···X or C–H···X (X = O, N or Cl) hydrogen bonds. For complex 2, an interesting macrocyclic tetramer has been built by the intermolecular N–H···O hydrogen bonds. Fascinatingly, two unique symmetric dimeric structures are recognized in complexes 7 and 8, which is individually bridged by intermolecular N–H···Cl and N–H···O hydrogen bonds. In addition, for 8, the dimeric cycles have been further connected into a 1D supramolecular chain.

Synthetic methods : Part (ii) Oxidation and reduction methods

This Report highlights advances in some of the most commonly used oxidation and reduction reactions, focusing on the literature from 2008. Significant advances in oxidation chemistry include site-selective epoxidation of polyprenols,6 bis(hydroxamic acid) ligands for vanadium(V)-catalysed highly enantioselective epoxidation of cis-disubstituted olefins,40 a direct catalytic aziridination of styrenes with ammonia112 and an aerobic ruthenium-catalysed alkene to aldehyde oxidation displaying non-Wacker regiochemistry.133 Significant advances in reduction chemistry include adaptive supramolecular “METAMORPhos” ligands for asymmetric alkene hydrogenation,160 early main-group metal catalysts for alkene hydrogenation181 and the use of “frustrated Lewis pairs” to effect H2 bond scission for imine and nitrile reduction.191

Highly Fluorescent Group 13 Metal Complexes With Cyclic, Aromatic Hydroxamic Acid Ligands

The neutral complexes of two ligands based on the 1-oxo-2-hydroxy-isoquinoline motif with group 13 metals (Al, Ga, In) show bright blue-violet luminescence in organic solvents. The corresponding transition can be attributed to ligand-centered singlet emission, characterized by a small Stokes shifts of only a few nanometers combined with lifetimes in the range between 1 and 3 ns. The fluorescence efficiency is high, with quantum yields of up to 37% in benzene solution. The crystal structure of one of the indium(III) complexes (trigonal space group R3, a = b = 13.0384(15) A, c = 32.870(8) A, alpha = beta = 90 degrees , gamma = 120 degrees , V = 4839.3(14) A (3), Z = 6) shows a six-coordinate geometry around the indium center, which is close to trigonal-prismatic, with a twist angle between the two trigonal faces of 20.7 degrees . Time-dependent density functional theory calculations (Al and Ga, B3LYP/6-31G(d); In, B3LYP/LANL2DZ) of the fac and mer isomers with one of the two ligands indicate that there is no clear preference for either one of the isomeric forms of the metal complexes. In addition, the metal centers do not have a significant influence on the electronic structure nor, as a consequence, on the predominant intraligand optical transitions.

Efficient Route to Highly Water‐Soluble Aromatic Cyclic Hydroxamic Acid Ligands

Abstract2‐Hydroxyisoquinolin‐1‐one (1,2‐HOIQO) is a new member of the important class of aromatic cyclic hydroxamic acid ligands which are widely used in metal sequestering applications and metal chelating therapy. The first general approach for the introduction of substituents at the aromatic ring of the chelating moiety is presented. As a useful derivative, the highly water‐soluble sulfonic acid has been synthesized by an efficient route that allows general access to 1,2‐HOIQO 3‐carboxylic acid amides, which are the most relevant for applications. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A Simple and Efficient Catalyst System for the Asymmetric Transfer Hydrogenation of Ketones

Aryl alkyl ketones are efficiently and selectively reduced (up to 97% ee) under transfer-hydrogenation conditions in 2-propanol using rhodium catalysts based on readily available amino acid derived hydroxamic acid ligands.

Bis(N-oxidonicotinamidium-κ2O,O′)diperchloratocopper(II)

The title compound, [Cu(ClO4)2(C6H6N2O2)2], contains neutral mol­ecules of a centrosymmetric mononuclear copper(II) complex, in which the zwitterionic hydroxamic acid ligand is O,O′-chelated to the CuII atom. The CuII atom lies on an inversion centre and has a distorted tetragonal-bipyramidal environment, being coordinated by four O atoms of the two N-hydroxy­nicotinamide mol­ecules forming the equatorial plane, and by two O atoms of the perchlorate anions occupying the axial positions.

Vanadium-Catalyzed Asymmetric Epoxidation: Proline-Derived Hydroxamic Acids Revisited

Structural features of ligands and substrates affecting enantioselectivity in vanadium(V)-catalyzed epoxidation of allylic alcohols were investigated. For the hydroxamic acid ligands derived from arylhydroxylamines, 2-aryl-substituted allylic alcohols emerged as the best substrates furnishing good level of enantio­selectivity.

Infrared Spectroscopic Studies of Siderophore-Related Hydroxamic Acid Ligands Adsorbed on Titanium Dioxide

The adhesion of bacteria to metal oxide and other mineral surfaces may involve bacterial siderophores, many of which contain hydroxamic acid (Ha) ligands. The adsorption behavior of the siderophore-related ligands acetohydroxamic acid, N-methylformohydroxamic acid, N-methylacetohydroxamic acid, and 1-hydroxy-2-piperidone on titanium dioxide thin films has been investigated using in situ ATR-IR spectroscopy with variation of concentration and pH. All the ligands were found to adsorb strongly on the TiO2 surface as hydroxamate ions and form bidentate surface complexes. Vibrational modes involving C=O stretching and N-O stretching of these ligands were assigned by comparing observed IR spectra with those calculated by the density functional method at the B3LYP/6-31+G(d) level. Calculated spectra of the complex [Ti(Ha)(OH)4]-, used to model the TiO2 surface, were compared with observed spectra of adsorbed hydroxamic acids. These results suggest that hydroxamic acid ligands in siderophores would be expected to bind to metal (oxide) and mineral surfaces during bacterial adhesion processes.

Tuning the oxidation properties of vanadium(V) through ligand stoichiometry

Vanadium(V) (5 mol %) and hydroxamic acid ligand (45 mol %) were found to promote the selective tert-butyl hydroperoxide-mediated oxidation of allylic and propargylic alcohols to the corresponding aldehydes and ketones.

Formation and Structure of 1:1 Complexes between Aryl Hydroxamic Acids and Vanadate at Neutral pH

Although aryl hydroxamic acids are well-known to form coordination complexes with vanadate (V(V)), the nature of these complexes at neutral pH and submillimolar concentrations, the conditions under which such complexes inhibit various serine amidohydrolases, is not well established. A series of qualitative and quantitative experiments, involving UV/vis, (1)H NMR, and (51)V NMR spectroscopies, established that both 1:1 and 1:2 vanadate/hydroxamate complexes form at pH 7.5, with the former dominating at submillimolar concentrations. Formation constants for the complexes of several aryl and alkyl hydroxamic acids were determined; for example, for benzohydroxamic acid, the stepwise formation constants of the 1:1 and 1:2 complexes were 3000 and 400 M(-1), respectively. The (51)V chemical shift of the 1:1 4-nitrobenzohydroxamic acid complex was -497 ppm, and that of its unsubstituted analogue was -498 ppm. A (1)H-(15)N HSQC spectrum of the 4-nitrobenzo-(15)N-hydroxamic acid/vanadate complex indicated the presence of an N-H group with (15)N and (1)H chemical shifts of 115 and 5.83 ppm, respectively. A (13)C NMR spectrum of the complex of 4-nitrobenzo-(13)C-hydroxamic acid with vanadate displayed a resonance at 170.1 ppm and thus a coordination-induced shift (CIS) of +3.8 ppm. In contrast, the CIS value of an established 1:2 complex, thought to contain chelated hydroxamic acid ligands, was +11.9 ppm. These spectral data led to the following structural picture of 1:1 complexes of vanadate and aryl hydroxamic acids. They contain penta- or hexa-coordinated vanadium. The ligand is in the hydroxamate rather than hydroximate form. The ligand is presumably bound to vanadium through the hydroxamic hydroxyl oxygen, but the hydroxamic acid carbonyl oxygen interacts weakly with vanadium. These species are the most likely candidates for the inhibitors of serine amidohydrolases found in vanadate/hydroxamic acid mixtures.

Novel α-Amino Acid-Based Hydroxamic Acid Ligands for Vanadium-Catalyzed Asymmetric Epoxidation of Allylic Alcohols

Novel α-Amino Acid-Based Hydroxamic Acid Ligands for Vanadium-Catalyzed Asymmetric Epoxidation of Allylic Alcohols