Dizinc Complex Research Articles

An aniline-bridged bis(pyrazolyl)alkane ligand for dizinc-catalysed ring-opening polymerization.

We report an aniline ligand (1) with two bis(pyrazolyl)alkane arms, and its cationic, dizinc complexes. XRD, NMR, and modelling of the dizinc complexes resulted in an unprecedented, dynamic μ-anilide core. Compared with published μ-phenolate analogues, our μ-anilide complexes show higher activity and divergent counterion trends in ring-opening polymerization of rac-lactide.

Bimetallic polymerization of lactide with binaphthol-derived bis-heteroscorpionate dizinc and dimagnesium complexes.

Discrete bimetallic catalysts often provide enhanced reactivity and selectivity in lactone polymerization, making metal-metal cooperativity an important design principle for new catalyst development. However, the poor modularity of binucleating ligands limits structure-reactivity analysis and optimization. This report describes a modular, binucleating bis(pyrazolyl)alkane ligand series (1-R) bridged by a chiral binaphthol unit, prepared by nucleophile-catalyzed condensation between a dialdehyde and a bis(pyrazolyl)methanone. A bis(ethylzinc) complex was characterized by single-crystal X-ray diffraction, but in situ complexation with Zn(HMDS)2 and Mg(HMDS)2 provided more active catalysts for lactide polymerization (HMDS- = hexamethyldisilazide). Structure-reactivity studies identified complexes of 1-Me2 as the most active, and these catalysts show significant enhancements in rate compared to their monometallic analogues. Kinetic analysis resulted in first-order dependence on both mono- and bimetallic catalysts, suggesting metal-metal cooperativity as the basis for this rate enhancement. End-group analysis and low dispersity implicate a coordination-insertion mechanism through an alkoxide. Despite rapid transesterification observed by MALDI, we still demonstrated controlled polymerization in the block copolymerization of ε-caprolactone and L-lactide. Although we observed rate differences in the polymerization of L-lactide by opposite enantiomer catalysts, we did not observe catalyst-directed stereoselectivity in the polymerization of rac- or meso-lactide.

Binucleating Bis(pyrazolyl)alkane Ligands and Their Cationic Dizinc Complexes: Modular, Bimetallic Catalysts for Ring-Opening Polymerization

Binucleating ligands enable the rational study and utilization of metal–metal cooperativity in catalysis through discrete bimetallic complexes. However, binucleating ligands rarely show the degree of structural modularity required for detailed optimization or structure–activity analysis, which are fundamental to homogeneous metal catalysis. This report introduces a highly modular family of binucleating proligands (1-R) consisting of two bis(pyrazolyl)alkanes bridged by a phenol. We prepared this series of proligands with variable substituents (R = −H, −Me, −Ph, −iPr) at the pyrazole 3-position in good yields by nucleophile-catalyzed condensation between 2,6-diformyl-4-(tert-butyl)-phenol and the corresponding bis(pyrazolyl)methanones. Cationic dizinc complexes 6-R were then prepared by treating proligands 1-R with diethylzinc and trityl salts. We fully characterized complex 6-H by single-crystal X-ray diffraction, identifying a twisted structure and modeling its conformational dynamics by density functional theory. The zinc atoms in 6-H are distorted tetrahedral, favorable for main group metals. Catalytic comparison identified 6-H as the most active and controlled catalyst for lactide and ε-caprolactone polymerization, resulting in low dispersity, end-group incorporation, and block copolymerization. Complexes 6-R represent the first atom-bridged bis(pyrazolyl)alkane bimetallics and constitute a highly modular platform for the rational investigation of dinuclear main group catalysis.

Design, Synthesis and Biological Evaluation of Boron‐Containing Macrocyclic Polyamine Dimers and Their Zinc(II) Complexes for Boron Neutron Capture Therapy

AbstractBoron neutron capture therapy (BNCT) is considered to have potential for cancer therapy based on the nuclear reaction between boron (10B) atoms and thermal neutrons, yielding 4He2+ (α) and 7Li3+ ions. These heavy particles induce the destruction of biomolecules within short path length of 5–9 μm, resulting in a limited cytotoxic effect to 10B‐containing cells. Herein, we report on the design and synthesis of DNA‐targeting BNCT agents equipped with homo‐ and hetero‐dimeric macrocyclic polyamine units and their Zn2+ complexes. It was hypothesized that the dizinc(II) complexes of these ligands would recognize two adjacent thymidines (thymidyl(3'–5')thymidine), resulting in an efficient contact with DNA and an efficient breakdown of DNA upon thermal neutron irradiation. To test this hypothesis, we performed a DNA interaction study and a biological evaluation such as cytotoxicity and intracellular uptake activity using cancer and normal cells. BNCT experiments utilizing the corresponding 10B‐enriched compounds were also conducted.

On the nature of bonding in a new boronyl species Zn2(BO)2: a linear four-center two-electron σ bond.

The Zn-Zn bond as one of the metal-to-metal bonds in clusters and molecules is of fundamental interest in many areas of natural science. Neutral boronyl can be viewed as a σ radical and is found in boronyl metal complexes. However, a complex with the Zn-Zn bond stabilized by boronyl ligands has not been found so far. Herein, we report on the computational design of the simplest case of such a system: linear D∞h OBZnZnBO. The structural and electronic properties and chemical bonding on a series of zinc complexes Znx(BO)y (x = 1,2; y = 1,2) with boronyl as ligands have been studied using quantum chemical calculations at the B3LYP and PBE0 levels, respectively. For the Zn2(BO)2 cluster, the linear D∞h OBZnZnBO is the global minimum, in which the calculated Zn-Zn bond length of rZn-Zn = 2.400 Å at the B3LYP level, which appears to be close to the latest recommended covalent radii (2.40 Å) of the proposed single bond covalent radii of the Zn-Zn bond. Chemical bonding analyses show that D∞h OBZnZnBO possesses a linear four-center two-electron (4c-2e) σ bond. The σ bond framework has a contribution of Zn orbitals 54% and B orbitals 44%, which involve Zn 4s 20% and 4p 34%, and B 2s 28% and 2p 16%, respectively. Furthermore, the D∞h HZnZnH and NCZnZnCN clusters also exhibit one linear 4c-2e σ bond due to the secondary contribution from the H s and C sp components, respectively. The linear 4c-2e σ bond greatly stabilizes the dizinc complexes. D∞h OBZnZnBO is thermochemically stable with respect to the possible formation channel at room temperature, whereas the formation energy of the exergonic channel, 2ZnBO (C∞v, 2Σg) → OBZnZnBO (D∞h, 1Σg), is evaluated to be -58.75 kcal mol-1 at the B3LYP level. Thus, D∞h OBZnZnBO as the first observation of the Zn-Zn covalent bond in zinc complexes with boronyl as ligands may be synthesized in laboratories in the near future.

Ring-opening polymerization of ε-caprolactone mediated by a di-zinc complex bearing a macrocyclic thioether-phenolate [OSSO]-type ligand

A unique example of zinc bromide complexes bearing a macrocyclic [OSSO]-type thioetherphenolate ligand has been successfully explored toward ring-opening polymerization of ε-caprolactone in the presence of epoxides and onium salts.

Synthesis, structural, characterization and Hirshfeld analysis of a bisselenide and a zinc complex of a new hemilabile ferrocenylbisphosphane, [Fe{C5H4P(C6H4CH2NMe2-o)2}2

The novel hemilabile ferrocenylbisphosphane 1,1'-bis(bis{2-[(dimethylamino)methyl]phenyl}phosphanyl)ferrocene, [Fe{C5H4P(C6H4CH2NMe2-o)2}2] (1), was synthesized by reacting bis(dichlorophosphanyl)ferrocene, [Fe{C5H4(PCl2)}2] with LiC6H4CH2NMe2-o. Treatment of 1 with gray selenium and anhydrous ZnCl2 yielded, respectively, the bisselenide (ferrocene-1,1'-diyl)bis(bis{2-[(dimethylamino)methyl]phenyl}phosphine selenide), [Fe(C23H28N2PSe)2] (2), and the dizinc complex [μ-1,1'-bis(bis{2-[(dimethylamino)methyl]phenyl}phosphanyl)ferrocene-κ2N,P:κ2N',P']bis[dichloridozinc(II)] dichloromethane monosolvate, [FeZn2Cl4(C23H28N2P)2]·CH2Cl2 (3), and both have been structurally characterized. Both compounds crystallized with the asymmetric unit containing half a molecule and with the Fe atom on an inversion centre. A Hirshfeld surface analysis indicated that the most significant contributions to the crystal packing of 2 are from H...H (76.7%), C...H/H...C (13.2%) and Se...H/H...Se (7.1%) contacts, while those for 3 are from H...H (62.3%), Cl...H/H...Cl (24.4%) and C...H/H...C (10.9%) contacts.

Exploring the Ability of Luminescent Metal Assemblies to Bind and Sense Anionic or Ionizable Analytes A Ru(phen)2bipy-Based Dizinc Complex for Bisphenol A (BPA) Recognition.

The synthesis of a new RuII complex, in which the metal is coordinated by two 1,10-phenanthroline ligands and a 2,2′-bipyridyl unit linked, via methylene bridges in its 4 and 4′ positions, to two 1,4,7,10-tetraazacyclododecane (cyclen) macrocycles ([Ru(phen)2L]2+) is reported. Protonation and ZnII binding by [Ru(phen)2L]2+ have been analyzed by potentiometric titration, evidencing the formation of mixed hetero-binuclear and hetero-trinuclear ZnII/RuII complexes. These complexes were tested as bis-phenol A (BPA) binders. Only the dizinc complex with [Ru(phen)2L]2+ is able to bind BPA in aqueous solution, affording a remarkably stable {Zn2[Ru(phen)2L]BPA(H−2)}4+ adduct at neutral pH, in which BPA is bound in its doubly deprotonated form to the two ZnII ions. BPA binding was found to quench the luminescence emission of the RuII(phen)2bipy core. Although the quenching effect is modest, this study demonstrates that appropriately designed dizinc complexes can be used for binding and optical sensing of BPA in water.

Phos-Tag Fluorescent Gel Staining for the Quantitative Detection of His- and Asp-Phosphorylated Proteins.

We describe a standard protocol for phosphate-affinity fluorescent gel staining that uses a fluorophore-labeled dizinc(II) complex of a derivative of the phosphate-binding tag molecule Phos-tag to detect His- and Asp-phosphorylated proteins separated by SDS-PAGE. The procedure permits the quantitative monitoring of phosphorylated histidine kinases (His-phosphoproteins) and their cognate phosphorylated response regulators (Asp-phosphoproteins) in bacterial two-component signaling transduction systems. The total time required for each gel staining operation is about 2h at room temperature.

Monitoring inorganic pyrophosphatase activity with the fluorescent dizinc(ii) complex of a macrocycle bearing one dansylamidoethyl antenna.

The dizinc(ii) complexes of L were used for the recognition of anions by fluorescence spectroscopy (L is a heteroditopic hexaazamacrocycle with two diethylenetriamine coordination heads with 2-methylpyridyl and dansylamido ethyl arms, and m-xylyl spacers). The protonation of L and stability constants of its zinc(ii) complexes were determined in aqueous solution, at 298.2 ± 0.1 K and I = 0.10 ± 0.01 M in KNO3. At a 2 : 1 Zn2+/L ratio, the dinuclear complexes clearly dominate. The ligand alone does not display fluorescence changes upon increasing the pH value, but in the presence of Zn2+ the emission reaches a maximum at pH ≅ 7.5, at which 95% of the ligand is in the dinuclear complex form. The emission appears concomitantly with the [Zn2H-1L]3+ species formation, which supports that the latter complex corresponds to the metal-promoted deprotonation of dansylamide NH. The [Zn2H-1L]3+ complexes were used for the recognition of phosphate and polyphosphate anions in aqueous solution buffered at pH 7.5 with 2 mM PIPPS, at 298.2 K. The binding of anions causes a decrease of the emission. The association constant determination revealed that HPPi3- is the strongest bound anion (log Kapp = 5.57), followed by HATP3- (two times weaker), and the remaining anions show lower binding constants, with HPO42- having the weakest uptake by the receptor. The observed selectivity of the [Zn2H-1L]3+ receptor for PPi in relation to HPO42-, and the fact that the formation of the [Zn2H-1L]3+ complex is not disturbed by the presence of Mg2+, allowed monitoring of the PPi hydrolysis by using inorganic pyrophosphatase in real-time.

Neighbouring effects on catalytic epoxidation by Fe-cyclam in M2-PDIxCy complexes.

The unsymmetric PDIeCy ligand, featuring pyridinediimine and cylam sites, can be selectively metalated. Complementing the diiron compound, we have synthesized two heterobimetallic isomers, [ZnPDIFeCy(PDIeCy)(OTf)4] (3) and [FePDIZnCy(PDIeCy)(OTf)4] (4), and a dizinc complex, [Zn2(PDIeCy)(OTf)4] (5). Olefin epoxidation by the series of complexes was investigated. The M-PDI site influences the reactivity of the M-cyclam, resulting in increased activity toward enones.

Molecular recognition of bisphosphonate-based drugs by di-zinc receptors in aqueous solution and on gold nanoparticles.

Metal-based anion receptors have several important applications in sensing, separation and transport of negatively charged species. Amongst these receptors, di-zinc(ii) complexes are of particular interest for the recognition of oxoanions, in particular phosphate derivatives. Herein we report the synthesis of a di-zinc(ii) receptor and show that it has high affinity and selectivity for bisphosphonates such as alendronate and etidronate - which are used to treat a number of skeletal disorders as well as showing interesting anticancer properties. The binding mode of the di-zinc(ii) receptor with alendronate and etidronate has been unambiguously established by single crystal X-ray crystallography. In addition, by modifying the backbone of the receptor, we show that the drug-loaded receptor can be attached onto gold nanoparticles as potential drug-delivery vehicles.

Formation of Short Zn-Zn Bonds Stabilized by Simple Cyanide and Isocyanide Ligands.

Cyanogen diluted in argon was reacted with laser ablated Zn atoms to produce the NCZnCN and NCZnZnCN cyanides and higher energy isocyanides ZnNC, CNZnNC, and CNZnZnNC, which were isolated in excess argon at 4 K. These reaction products, identified from the matrix infrared spectra of their -CN and -NC chromophore ligand stretching modes, were confirmed by 13 C and 15 N isotopic substitution and comparison with frequencies calculated by the B3LYP and CCSD(T) methods using the all electron aug-cc-pVTZ basis sets. The cyanide and isocyanide products were increased markedly by mercury arc UV photolysis, which covers the zinc atomic absorption. The above electronic structure calculations that produce appropriate ligand frequencies for these dizinc products also provide their Zn-Zn bond lengths: CCSD(T) calculations find a short 2.367 Å Zn-Zn bond in the NCZnZnCN cyanide, a shorter 2.347 Å Zn-Zn bond in the 37.4 kJ mol-1 higher energy isocyanide CNZnZnNC, and a longer 4.024 Å bond in the dizinc van der Waals dimer. Thus, the diatomic cyanide (-CN) and isocyanide (-NC) ligands are as capable of stabilizing the Zn-Zn bond as many much larger ligands based on their measured and our calculated Zn-Zn bond lengths. This is the first example of dizinc complexes stabilized by different ligand isomers. Additional weaker bands in this region can be assigned to the analogous trizinc molecules NCZnZnZnCN and CNZnZnZnNC.

Formation of Short Zn−Zn Bonds Stabilized by Simple Cyanide and Isocyanide Ligands

AbstractCyanogen diluted in argon was reacted with laser ablated Zn atoms to produce the NCZnCN and NCZnZnCN cyanides and higher energy isocyanides ZnNC, CNZnNC, and CNZnZnNC, which were isolated in excess argon at 4 K. These reaction products, identified from the matrix infrared spectra of their ‐CN and ‐NC chromophore ligand stretching modes, were confirmed by 13C and 15N isotopic substitution and comparison with frequencies calculated by the B3LYP and CCSD(T) methods using the all electron aug‐cc‐pVTZ basis sets. The cyanide and isocyanide products were increased markedly by mercury arc UV photolysis, which covers the zinc atomic absorption. The above electronic structure calculations that produce appropriate ligand frequencies for these dizinc products also provide their Zn−Zn bond lengths: CCSD(T) calculations find a short 2.367 Å Zn−Zn bond in the NCZnZnCN cyanide, a shorter 2.347 Å Zn−Zn bond in the 37.4 kJ mol−1 higher energy isocyanide CNZnZnNC, and a longer 4.024 Å bond in the dizinc van der Waals dimer. Thus, the diatomic cyanide (‐CN) and isocyanide (‐NC) ligands are as capable of stabilizing the Zn−Zn bond as many much larger ligands based on their measured and our calculated Zn−Zn bond lengths. This is the first example of dizinc complexes stabilized by different ligand isomers. Additional weaker bands in this region can be assigned to the analogous trizinc molecules NCZnZnZnCN and CNZnZnZnNC.

Correction to "Catalytic Hydrolysis of Phosphate Monoester by Supramolecular Phosphatases Formed from a Monoalkylated Dizinc(II) Complex, Cyclic Diimide Units, and Copper(II) in Two-Phase Solvent System".

Correction to "Catalytic Hydrolysis of Phosphate Monoester by Supramolecular Phosphatases Formed from a Monoalkylated Dizinc(II) Complex, Cyclic Diimide Units, and Copper(II) in Two-Phase Solvent System".

Catalytic Hydrolysis of Phosphate Monoester by Supramolecular Phosphatases Formed from a Monoalkylated Dizinc(II) Complex, Cyclic Diimide Units, and Copper(II) in Two-Phase Solvent System.

Design and synthesis of enzyme mimic with programmed molecular interaction among several building blocks including metal complexes and metal chelators is of intellectual and practical significance. The preparation of artificial enzymes that mimic the natural enzymes such as hydrolases, phosphatases, etc. remains a great challenge in the field of supramolecular chemistry. Herein we report on the design and synthesis of asymmetric (nonsymmetric) supermolecules by the 2:2:2 self-assembly of an amphiphilic zinc(II)-cyclen complex containing a 2,2'-bipyridyl linker and one long alkyl chain (Zn2L3), barbital analogues, and Cu2+ as model compounds of an enzyme alkaline phosphatase that catalyzes the hydrolysis of phosphate monoesters such as mono(4-nitrophenyl)phosphate at neutral pH in two-phase solvent system (H2O/CHCl3) in pH 7.4 and 37 °C. Hydrolytic activity of these complexes was found to be catalytic, and their catalytic turnover numbers are 3-4. The mechanistic studies based on the UV/vis and emission spectra of the H2O and CHCl3 phases of the reaction mixtures suggest that the hydrophilicity/hydrophobicity balance of the supramolecular catalysts is an important factor for catalytic activity.

Mechanistic Studies of Homo- and Heterodinuclear Zinc Phosphoesterase Mimics: What Has Been Learned?

Phosphoesterases hydrolyze the phosphorus oxygen bond of phosphomono-, di- or triesters and are involved in various important biological processes. Carboxylate and/or hydroxido-bridged dizinc(II) sites are a widespread structural motif in this enzyme class. Much effort has been invested to unravel the mechanistic features that provide the enormous rate accelerations observed for enzymatic phosphate ester hydrolysis and much has been learned by using simple low-molecular-weight model systems for the biological dizinc(II) sites. This review summarizes the knowledge and mechanistic understanding of phosphoesterases that has been gained from biomimetic dizinc(II) complexes, showing the power as well as the limitations of model studies.

Selective sensing of ATP by hydroxide-bridged dizinc(ii) complexes offering a hydrogen bonding cavity.

This work illustrates the highly selective fluorescence detection of ATP in the presence of other competing anions, such as AMP, ADP, PPi and other phosphates by using a set of hydroxide-bridged dizinc(ii) complexes offering a cavity lined with hydrogen bonds and other interactive forces. ATP, as a whole, was recognized by the synergic combination of Zn-phosphate bonding, ππ stacking between the adenine ring of ATP and the pyridine ring of the dizinc complex and hydrogen bonding interactions that modulate the cavity structure of the dizinc complexes.

Interaction of Nucleotides with a Trinuclear Terbium(III)-Dizinc(II) Complex: Efficient Sensitization of Terbium Luminescence by Guanosine Monophosphate and Application to Real-Time Monitoring of Phosphodiesterase Activity.

An in-depth study of the interaction of a trinuclear terbium(III)-dizinc(II) complex with an array of nucleotides differing in the type of nucleobase and number of phosphate groups, as well as cyclic versus acyclic variants, is presented. The study examined the nature of the interaction and the efficiency at which guanine was able to sensitize terbium(III) luminescence. Competitive binding and titration studies were performed to help establish the nature/mode of the interactions. These established that (1) interaction occurs by the coordination of phosphate groups to zinc(II) (in addition to uridine in the case of uridine monophosphate), (2) acyclic nucleotides bind more strongly than cyclic counterparts because of their higher negative charge, (3) guanine-containing nucleotides are able to sensitize terbium(III) luminescence with the efficiency of sensitization following the order guanosine monophosphate (GMP) > guanosine diphosphate > guanosine triphosphate because of the mode of binding, and (4) nucleoside monophosphates bind to a single zinc(II) ion, whereas di- and triphosphates appear to bind in a bridging mode between two host molecules. Furthermore, it has been shown that guanine is a sensitizer of terbium(III) luminescence. On the basis of the ability of GMP to effectively sensitize terbium(III)-based luminescence while cyclic GMP (cGMP) does not, the complex has been utilized to monitor the catalytic conversion of cGMP to GMP by a phosphodiesterase enzyme in real time using time-gated luminescence on a benchtop fluorimeter. The complex has the potential to find broad application in monitoring the activity of enzymes that process nucleotides (co)substrates, including high-throughput drug-screening programs.

Front Cover: An Unsymmetric Ligand with a N5O2 Donor Set and Its Corresponding Dizinc Complex: A Structural and Functional Phosphoesterase Model (Eur. J. Inorg. Chem. 36/2018)

Front Cover: An Unsymmetric Ligand with a N₅O₂ Donor Set and Its Corresponding Dizinc Complex: A Structural and Functional Phosphoesterase Model (Eur. J. Inorg. Chem. 36/2018)