Diolate Complexes Research Articles

Oxygenolytic cleavage of 1,2-diols with dioxygen by a mononuclear nonheme iron complex: Mimicking the reaction of myo-inositol oxygenase

A mononuclear iron(II) complex, [(TpPh2)FeII(OTf)(CH3CN)] (1) (TpPh2 = hydrotris(3,5-diphenylpyrazol-1-yl)borate, OTf = triflate) has been isolated and its efficiency toward the aliphatic CC bond cleavage reaction of 1,2-diols with dioxygen has been investigated. Separate reactions between 1 and different 1,2-diolates form the corresponding iron(II)-diolate complexes in solution. While the iron(II) complex of the tetradentate TPA (tris(2-pyridylmethyl)amine) ligand is not efficient in affecting the CC cleavage of 1,2-diol with dioxygen, complex 1 displays catalytic activity to afford carboxylic acid and aldehyde. Isotope labeling studies with 18O2 reveal that one oxygen atom from dioxygen is incorporated into the carboxylic acid product. The oxygenative CC cleavage reactions occur on the 1,2-diols containing at least one α-H atom. The kinetic isotope effect value of 5.7 supports the abstraction of an α-H by an iron(III)-superoxo species to propagate the CC cleavage reactions. The oxidative cleavage of 1,2-diolates by the iron(II) complex mimics the reaction catalyzed by the nonheme diiron enzyme, myo-inositol oxygenase.

Cooperativity and topological hydrogen bonding in aromatic diol complexes

AbstractComplexes of three aromatic diols, catechol, naphthalene‐1,8‐diol, and fluorene‐4,5‐diol, with a series of hydrogen bond acceptors (HBAs) that have oxygen, nitrogen, and sulfur acceptor atoms, have been studied by density functional theory (DFT) at the B3LYP/6‐311+G(d,p) level. Binding energies, geometries, infrared spectroscopic (IR) frequencies, nuclear magnetic resonance (NMR) shifts, and measures of the electron density distribution from the Quantum Theory of Atoms in Molecules (QTAIM) are evaluated and compared with data for the corresponding monohydroxy compounds (monols), phenol, naphth‐1‐ol, and fluorene‐4‐ol, in order to assess the importance of cooperativity between intramolecular and intermolecular hydrogen bonding. All measures for all complexes show positive cooperativity whereby both the intermolecular and intramolecular hydrogen bonds are strengthened upon complexation. Cooperativity is weak for catechol and strong for the other two diols and, for all diols, increases with the hydrogen bond basicity of the acceptor. Correlations of IR and NMR metrics against binding energies for a single HBA and all six monols and diols are excellent, but attempts to correlate the same metrics for all HBAs and a single donor are frustrated by differences in intermolecular hydrogen bonding, depending notably on the identity of the acceptor atom in the HBA. Atom–atom interaction energies, calculated by the Interacting Quantum Atoms approach, are used to discuss the covalency of both types of hydrogen bond.

Viscoelastic hydrogels for interrogating pancreatic cancer-stromal cell interactions.

The tumor microenvironment (TME) is known to direct cancer cell growth, migration, invasion into the matrix and distant tissues, and to confer drug resistance in cancer cells. While multiple aspects of TME have been studied using in vitro, ex vivo, and in vivo tumor models and engineering tools, the influence of matrix viscoelasticity on pancreatic cancer cells and its associated TME remained largely unexplored. In this contribution, we synthesized a new biomimetic hydrogel with tunable matrix stiffness and stress-relaxation for evaluating the effect of matrix viscoelasticity on pancreatic cancer cell (PCC) behaviors in vitro. Using three simple monomers and Reverse-Addition Fragmentation Chain-Transfer (RAFT) polymerization, we synthesized a new class of phenylboronic acid containing polymers (e.g., poly (OEGA-s-HEAA-s-APBA) or PEHA). Norbornene group was conjugated to HEAA on PEHA via carbic anhydride, affording a new NB and BA dually modified polymer - PEHNBA amenable for orthogonal thiol-norbornene photopolymerization and boronate ester diol complexation. The former provided tunable matrix elasticity, while the latter gave rise to matrix stress-relaxation (or viscoelasticity). The new PEHNBA polymers were shown to be highly cytocompatible for in situ encapsulation of PCCs and cancer-associated fibroblasts (CAFs). Furthermore, we demonstrated that hydrogels with high stress-relaxation promoted spreading of CAFs, which in turns promoted PCC proliferation and spreading in the viscoelastic matrix. Compared with elastic matrix, viscoelastic gels upregulated the secretion of soluble proteins known to promote epithelial-mesenchymal transition (EMT). This study demonstrated the crucial influence of matrix viscoelasticity on pancreatic cancer cell fate and provided an engineered viscoelastic matrix for future studies and applications related to TME.

Zwitterion-neutral form equilibria and binding selectivity of pyridineboronic acids.

A 11B NMR study of 3-pyridineboronic acid at variable pH in water and 50 vol% aqueous dioxane confirms that the tautomeric equilibrium of the acid is shifted to the zwitterionic form in water, but to the molecular form in the mixed organic solvent. Interactions of 3- and 4-pyridineboronic acids with sialic acid, fructose and several other diols were studied by potentiometric titrations in a wide range of pH in water and water-organic mixtures. In all reaction media the stability of boronate complexes increases upon an increase in pH for neutral low acidic diols such as fructose and glucose but has the opposite trend for highly acidic sialic and lactic acids occurring as anionic species. The selectivity of pyridineboronic acids to sialate anions in an acidic medium is interpreted quantitatively by combining the pH-profiles with Brønsted type correlations for binding constants. In addition, mathematical expressions allowing one to predict the optimum pKa value of a boronic acid for the strongest binding of a given diol (sialic acid or fructose) at a given pH are suggested. The shifts in the tautomeric equilibrium induced by changing the solvent polarity in aqueous-organic mixtures are manifested in the magnitude of relative shifts of pKa of pyridineboronic acids induced by diol complexation.

Hydroboration of a Diolate Complex Obtained by Carbon Dioxide Capture with Acenaphthenediimine Aluminum Hydride

The reduction of diolate [{(dpp-bian)Al(μ-O2CH2)}2] (1), bearing a redox-active acenaphthene-1,2-diimine ligand (dpp-bian = 1,2-bis[(2,6-diisopropylphenyl)imino]-acenaphthene), by boranes has been studied. The reaction of 1 with HBpin proceeds with reduction of the C–O bonds in the −O–CH2–O– fragments and results in [{(dpp-bian)Al(OCH3)}(μ-O){Al(OBpin)(dpp-bian)}] (2) and pinBOCH3. The reduction of 1 by HBcat leads to the formation of the compound [{(dpp-bian)Al(μ-Cat)}2] (3) and (CH3OBO)3. BH3·SMe2 reduces diolate 1 to form the complex [{(dpp-bian)Al(OCH3)}(μ-O){Al(OCH2OBH2)(dpp-bian)}] (4). Compounds 2–4 have been characterized by electron paramagnetic resonance and infrared spectroscopy, and their molecular structures have been determined by single-crystal X-ray analysis. Density functional theory calculations have been performed to analyze the reaction energies and a possible mechanism of an initial stage as well as to explain the different product types.

New Titanium(IV)-Alkoxide Complexes Bearing Bidentate OO Ligand with the Camphyl Linker as Catalysts for High-Temperature Ethylene Polymerization and Ethylene/1-Octene Copolymerization.

In order to increase the thermal stability of olefin polymerization precatalysts, new titanium(IV) complexes with diolate ligands differing in the degree of steric hindrances were synthesized from readily available precursor (±)camphor. The structures of the complexes 1-2 were established by X-ray diffraction. Complexes 1-4 in the presence of an activator {EtnAlCl3-n + Bu2Mg} catalyzed the synthesis of UHMWPE with an Mv up to 10 million and a productivity of up to 3300 kg/molTi·atm·h. The obtained polymers are obviously characterized by a low density of macromolecular entanglement, which makes it possible to use the solid-phase method for their processing. The mechanical characteristics of the oriented UHMWPE films had a breaking strength up to 2.7 GPa and an elastic modulus of up to 151 GPa. The precatalysts 1-4 were also active in ethylene/1-octene copolymerization. The comonomer content was in the range of 1.4-4.6 mol%. The use of a rigid linker and an increase in the steric load of the diolate complexes ensured the thermal stability of the catalytic system in the range of 50-70 °C.

Novel titanium (IV) diolate complexes with thiophene-containing OSO-type ligand as pre-catalyst for ethylene polymerization and ethylene - propylene copolymerization

New titanium (IV) complexes with diolate ligand containing additional donor sulfur atom have been synthesized and characterized. Structure of complex 2 was established by X-ray diffraction. Titanium atom adopts a distorted tetrahedral geometry formed by oxygen atoms of two ligands and isopropoxy-groups. Activation of these complexes with {EtnAlCl3-n + Bu2Mg} led to a highly active catalytic system for ethylene polymerization with an activity up to 2 tons PE·molTi-1·atm-1·h-1. Linear ultrahigh molecular weight polyethylenes (1.9-5.7 106 Da) were obtained under these conditions. The obtained polyethylenes are suitable for the modern methods of polymer processing - the solventless solid state formation of super high-strength (breaking strength up to 2.6 GPa) and high-modulus (elastic modulus up to 164 GPa) oriented films and film tapes. The precatalysts 1-3 were also active in ethylene-propylene copolymerization producing copolymers with a content of propylene units in the range 28-33%. The influence of the nature of the «leaving» monodentate σ-ligands (Cl, OiPr and N(CH3)2) and the organoaluminum co-catalyst (Et2AlCl and Et3Al2Cl3) on the activity of catalytic systems and the properties of the resulting polymers were studied.

Recyclable nanoparticles based on a boronic acid-diol complex for the real-time monitoring of imprinting, molecular recognition and copper ion detection.

Molecularly imprinted polymers (MIPs) have now become one of the most remarkable materials in the field of molecular recognition. Although many efforts have been made to study the process and mechanism of molecular imprinting, it has not been possible to monitor the interactions between the template and the growing polymer chains under real-time experimental conditions. The behavior of the template-monomer complex during the whole polymerization process has remained largely unknown. In this work, we introduce a fluorescence technique that allows monitoring of the template-functional monomer complex during an actual imprinting process, as well as the real-time signaling of template binding and dissociation from the imprinted polymer. For the first proof-of-principle, we select Alizarin Red S (ARS) and 4-vinylphenylboronic acid as the template and functional monomer, respectively, to synthesize MIP particles via precipitation polymerization. As the formation of the template-functional monomer complex leads to strong fluorescence emission, it allows the status of the template binding to be monitored throughout the whole reaction process in real time. Using the same fluorescence technique, the kinetics of template binding and dissociation can be studied directly without particle separation. The hydrophilic MIP particles can be used as a scavenger to remove ARS from water. In addition, the MIP particles can be used as a recyclable sensor to detect Cu ions. As the Cu ion forms a stable complex with ARS, it causes ARS to dissociate from the MIP nanoparticles, leading to effective fluorescence quenching. The non-separation analytical method based on fluorescence measurement provides a convenient means to study molecular imprinting reactions and the kinetics of molecular recognition using imprinted polymers. The recyclable nanoparticle sensor allows toxic Cu ions to be detected directly in water in the range of 0.1-100 μM with a recovery of 84-95%.

Chiral Co-Crystals of (S)- or (R)-1,1′-Binaphthalene-2,2′-diol and Zn2Dy2 Tetranuclear Complexes Behaving as Single-Molecule Magnets

Chiral Co-Crystals of (<i>S</i>)- or (<i>R</i>)-1,1′-Binaphthalene-2,2′-diol and Zn₂Dy₂ Tetranuclear Complexes Behaving as Single-Molecule Magnets

Novel titanium(IV) diolate complexes with additional O‐donor as precatalyst for the synthesis of ultrahigh molecular weight polyethylene with reduced entanglement density: Influence of polymerization conditions and its implications on mechanical properties

New alkoxo‐titanium(IV) complexes with diolate ligand containing additional donor oxygen atom have been synthesized from readily available and scalable precursors. The structure of complex 4 was established by X‐ray diffraction. Titanium atom adopts a distorted tetrahedral geometry formed by six oxygen atoms of ligands. The resulting complexes 3–4 are moderately or highly active in ethylene polymerization in the presence of {EtnAlCl3–n + Bu2Mg} binary cocatalysts. The influence of the nature of the solvent, the organoaluminum cocatalyst and the polymerization temperature on the activity of catalytic systems, and the properties of the resulting polymers were studied. The obtained polymers are linear polyethylene of ultrahigh molecular weight (up to 5.8·106 g mol−1) with a broad molecular weight distribution. The polymers are suitable for the modern methods of polymer processing—the solventless solid‐state formation of super high‐strength (breaking strength up to 2.8 GPa) and high‐modulus (elastic modulus up to 140 GPa) oriented films and film tapes. The possibility of scaling up the synthesis of ultrahigh molecular weight polyethylene (UHMWPE) without a significant drop in the productivity of the catalytic system and polymer properties is shown. UHMWPE samples have been investigated by small‐angle X‐ray scattering (SAXS) methods to study the structural changes induced by solid‐state drawing of nascent reactor powders.

Enantioselective Desymmetrization of 2-Aryl-1,3-propanediols by Direct O-Alkylation with a Rationally Designed Chiral Hemiboronic Acid Catalyst That Mitigates Substrate Conformational Poisoning.

Enantioselective desymmetrization by direct monofunctionalization of prochiral diols is a powerful strategy to prepare valuable synthetic intermediates in high optical purity. Boron acids can activate diols toward nucleophilic additions; however, the design of stable chiral catalysts remains a challenge and highlights the need to identify new chemotypes for this purpose. Herein, the discovery and optimization of a bench-stable chiral 9-hydroxy-9,10-boroxarophenanthrene catalyst is described and applied in the highly enantioselective desymmetrization of 2-aryl-1,3-diols using benzylic electrophiles under operationally simple, ambient conditions. Nucleophilic activation and discrimination of the enantiotopic hydroxy groups on the diol substrate occurs via a defined chairlike six-membered anionic complex with the hemiboronic heterocycle. The optimal binaphthyl-based catalyst 1g features a large aryloxytrityl group to effectively shield one of the two prochiral hydroxy groups on the diol complex, whereas a strategically placed "methyl blocker" on the boroxarophenanthrene unit mitigates the deleterious effect of a competing conformation of the complexed diol that compromised the overall efficiency of the desymmetrization process. This methodology affords monoalkylated products in enantiomeric ratios equal or over 95:5 for a wide range of 1,3-propanediols with various 2-aryl/heteroaryl groups.

Tuning the sensitivity towards mercury via cooperative binding to d-fructose: dual fluorescent chemosensor based on 1,8-naphthyridine-boronic acid derivative.

A novel fluorescent chemosensor naphthyridine-boronic acid derivative (1.1) was synthesized and its ability to act as a selective chemosensor was examined for various metal ions. Compound 1.1 displayed highly selective fluorescence quenching upon interaction with Hg2+, possibly by means of photo induced electron transfer (PET) mechanism. The binding stoichiometry of the naphthyridine-boronic acid–Hg2+ complex and the association constant was determined. It was found that in the presence of d-fructose at physiological concentration, the sensitivity of chemosensor 1.1 towards Hg2+ improved by at least 7 times, perhaps as a result of the cooperative binding of both d-fructose and mercury ion to the sensor. Till now, the presented dual d-fructose–mercury chemosensor is the first example of utilizing boronic acid–diol complexation for enhancement of the sensor's sensitivity towards a toxic metal ion. The utility of compound 1.1 lays in applications in the food industry, e.g. for detection of mercury contamination of high fructose corn syrup, or in estimation of mercury in polluted biological samples and underground water.

Ultrafast high-resolution analysis of human milk oligosaccharides by multicapillary gel electrophoresis

There is recently growing interest towards synthesized human milk oligosaccharides (HMOs) as baby formula additives, and interestingly also as dietary supplements for adults. Currently quite a few manufacturers synthesize HMOs, however, their analysis is challenging, both in resolution and speed. In this paper an ultrafast high-resolution method is introduced for the separation of HMOs by multicapillary gel electrophoresis. Two gel compositions were evaluated with complementary resolving power. One was a conventionally used industrial standard carbohydrate separation matrix, resolving oligosaccharides according to their charge to hydrodynamic volume ratios. The other one was a borate-buffered dextran gel, which utilized the secondary equilibrium of the borate-vicinal diol complexation to enhance resolution. Considering the rapid analysis time and multiplexing (12-channel system), a 96 well sample plate can be analyzed in less than 80 min with the conventional type carbohydrate separation matrix and in less than one hour with the borate-buffered dextran gel. Exploiting the one fluorophore per molecule labeling stoichiometry, the limit of detection (S/N > 3) and limit of quantitation (S/N > 10) were determined as 0.025 and 0.100 mg/mL, respectively, with good linearity. Based on the calibration plot, the quantities of several low concentration HMOs were determined from a human milk sample.

Fluoride Ion Interactions in Alkali-Metal Fluoride-Diol Complexes.

The activity of F- is an important factor in the design of both inorganic and organic reactions involving fluorine compounds. The present study investigates interactions of F- with diols in alkali-metal fluoride-diol complexes. Increases in the reactivities of alkali-metal fluorides and their solubilities in alcohols is observed with increasing cation size. The difference in alkali-metal ion size produces different structural motifs for F--diol complex salts. The CsF complex salt with ethylene glycol (EG), CsF-EG, has a layered structure, whereas the Rb and K complex salts, (RbF)5-(EG)4 and (KF)5-(EG)4, form columnar structures. Comparison of the CsF complex salts with three different diols- EG, 1,3-propylene glycol (PG13), and 1,4-butylene glycol (PG14)-revealed that the diol chain length affects the bridging mode in their layered structures. EG bridges two OH oxygen atoms within the same CsF layer in CsF-EG, whereas PG13 and BG14 bridge two OH oxygen atoms in different CsF layers in (CsF)2-PG13 and CsF-BG14, respectively. The F- ion coordination environment involves interactions between alkali-metal ions and H atom(s) in the diol OH groups, where the F-···H interactions are more dominant than the F-···M+ interaction, based on Hirshfeld surface analyses. The O-H bond weakening observed by infrared spectroscopy also reflects the strengths of the F-···H interactions in these complex salts.

Self-crosslinking smart hydrogels through direct complexation between benzoxaborole derivatives and diols from hyaluronic acid

By tailoring the structure of benzoxaborole (BOR), self-crosslinking hydrogels based on hyaluronic acid (HA) modified with BOR derivatives are obtained for the first time through the direct BOR-HA diol complexation at physiological pH.

Glucose-Responsive Polymeric Micelles via Boronic Acid-Diol Complexation for Insulin Delivery at Neutral pH.

In the present study, glucose-responsive polymeric complex micelles based on the complexation of phenylboronic-acid-based (PBA-based) block copolymer and diol-functionalized polymers are reported. The phenylboronic-acid- and diol-based block copolymers were successfully synthesized in only two reaction steps using reversible addition-fragmentation chain-transfer (RAFT) polymerization and postpolymerization modification of the obtained poly[( N-acryloylmorpholine- block-( N-acryloylmorpholine- co-pentafluorophenyl acrylate)], poly[(AMP- b-(AMP- co-PFPA)], reactive block copolymer. The self-assembly of the complex micelles was investigated under neutral conditions using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The interaction of the PBA block copolymer and diol-containing polymer via boronate ester bond was investigated by 1H NMR and UV-vis spectroscopy. The complex micelles enhanced the glucose responsiveness under physiological conditions compared to simple PBA micelles. Furthermore, the successful glucose-triggered release of FITC-insulin from the polymeric micelles was investigated.

Hydrogen-Bonded Networks: Molecular Recognition of Cyclic Alcohols in Enantiopure Alleno-Acetylenic Cage Receptors.

Enantiopure (P)4 - and (M)4 -alleno-acetylenic cage (AAC) receptors form circular fourfold hydrogen-bonding networks in their closed cage conformation. Theoretical studies reveal a preferential clockwise (cw) orientation of the H-bonding array for (P)4 -configured and counterclockwise (ccw) for (M)4 -configured receptors (ΔEcw-ccw =-2.6 to -3.1 kcal mol-1 ). Solution and solid-state studies show how the H-bonding network of the receptor is expanded upon encapsulation of alcohol-containing guests. Topologies reminiscent of those found in isolated water clusters are observed: circular fourfold & docking, pentagonal, linear fivefold, and hexagonal boat-shaped. Expansion of the H-bonding network together with optimal space occupancy yields very high ligand affinities (ΔG293 K =-9.0 kcal mol-1 for endo-tropine). The H-bonding network in the complexes also contributes substantially to the enantioselective complexation of chiral diols, such as (R,R)- and (S,S)-trans-cyclohexane-1,2-diol.

Asymmetric Diels-Alder Reaction of α,β-Unsaturated Oxazolidin-2-one Derivatives Catalyzed by a Chiral Fe(III)-Bipyridine Diol Complex.

An asymmetric FeIII-bipyridine diol catalyzed Diels-Alder reaction of α,β-unsaturated oxazolidin-2-ones has been developed. Among various FeII/FeIII salts, Fe(ClO4)3·6H2O was selected as the Lewis acid of choice. The use of a low catalyst loading (2 mol % of Fe(ClO4)3·6H2O and 2.4 mol % of Bolm's ligand) afforded high yields (up to 99%) and high enantiomeric excesses (up to 98%) of endo-cycloadducts for the Diels-Alder reaction between cyclopentadiene and substituted acryloyloxazolidin-2-ones. Other noncyclic dienes led to decreased enantioselectivities. A proposed model supports the observed stereoinduction.

Novel cerium(IV)-diolate complex with a 13-nuclear cerium(IV)-oxo core: Synthesis, molecular structure and catalytic property for ε-caprolactone-polymerization

The reaction of Ce(OtBu)2(NO3)2, prepared in situ from (NH4)2Ce(NO3)6 and tBuONa in a 1:4M ratio in THF, and N-phenyldiethanolamine (C6H5)N(CH2CH2OH)2 in a 1:1M ratio led to a brown solution, to which 1,10-phenanthroline (phen) was added. Yellow crystals of Ce(NO3)3(phen)2 and red crystals of Ce13O8[(OCH2CH2)2N(C6H5)]18 (1) were produced respectively at 40°C. Complex 1 is a novel polynuclear cerium(IV)-diolate compound with an 18 N-phenylaminediethanolate shell and a 13-nuclear cerium(IV)-oxo core. It catalyzed the polymerization of ε-caprolactone (CL) to produce PCL in very narrow molecular weight distribution.

Mixed Reversible Covalent Crosslink Kinetics Enable Precise, Hierarchical Mechanical Tuning of Hydrogel Networks.

Hydrogels play a central role in a number of medical applications and new research aims to engineer their mechanical properties to improve their capacity to mimic the functional dynamics of native tissues. This study shows hierarchical mechanical tuning of hydrogel networks by utilizing mixtures of kinetically distinct reversible covalent crosslinks. A methodology is described to precisely tune stress relaxation in PEG networks formed from mixtures of two different phenylboronic acid derivatives with unique diol complexation rates, 4-carboxyphenylboronic acid, and o-aminomethylphenylboronic acid. Gel relaxation time and the mechanical response to dynamic shear are exquisitely controlled by the relative concentrations of the phenylboronic acid derivatives. The differences observed in the crossover frequencies corresponding to pKa differences in the phenylboronic acid derivatives directly connect the molecular kinetics of the reversible crosslinks to the macroscopic dynamic mechanical behavior. Mechanical tuning by mixing reversible covalent crosslinking kinetics is found to be independent of other attributes of network architecture, such as molecular weight between crosslinks.