Evidence that protons can be the active catalysts in Lewis acid mediated hetero-Michael addition reactions

The mechanism of Lewis acid catalysed hetero‐Michael addition reactions of weakly basic nucleophiles to α,β‐unsaturated ketones was investigated. Protons, rather than metal ions, were identified as the active catalysts. Other mechanisms have been ruled out by analyses of side products and of stoichiometric enone–catalyst mixtures and by the use of radical inhibitors. No evidence for the involvement of π‐olefin–metal complexes or for carbonyl–metal‐ion interactions was obtained. The reactions did not proceed in the presence of the non‐coordinating base 2,6‐di‐tert‐butylpyridine. An excellent correlation of catalytic activities with cation hydrolysis constants was obtained. Different reactivities of mono‐ and dicarbonyl substrates have been rationalised. A ¹H NMR probe for the assessment of proton generation was established and Lewis acids have been classified according to their propensity to hydrolyse in organic solvents. Brønsted acid‐catalysed conjugate addition reactions of nitrogen, oxygen, sulfur and carbon nucleophiles are developed and implications for asymmetric Lewis acid catalysis are discussed.     

Derivatives of Coenzyme F430 with a Covalently Attached α‐Axial Ligand. Part I

X‐Ray structures of the enzyme methyl‐coenzyme M reductase show that the Ni‐center in the prosthetic group coenzyme F430 is penta‐ or hexacoordinated with the carboxamide group of a glutamine residue occupying the axial coordination site on the α‐side of the macrocycle. To obtain diastereoselectively coordinated complexes for mechanistic and spectroscopic studies of the free coenzyme in solution, we aimed to prepare partial‐synthetic derivatives of coenzyme F430 that have a coordinating group attached via a linker to one of the propanoic acid side chains. By using molecular‐mechanics calculations and two different conformational search methods, a set of 50 structures containing imidazole or pyridine units as potential ligands were computationally tested according to geometric criteria defining coordinating conformations. The best candidates proved to be proline‐containing tri‐ and tetrapeptides with a methyl‐histidine as the C‐terminal residue. These linkers were synthesized, and their conformation was determined by NMR. Refinement of the molecular modeling by using the experimentally determined geometric restraints allowed us to decide that the tripeptide Pro‐Pro‐His(π‐Me)‐OMe ( 10 ) was the most promising of all tested structures for attachment to the side chain at C(3) or C(13) of F430.     

The Hydrophobic and Metal-Ion Coordinating Properties of α-Lipoic Acid—An Example of Intramolecular Equilibria in Metal-Ion Complexes

Hydrophobic interactions as structure determining factors for macromolecules are well-known in biochemistry. Considerably less recognized is the fact that these law-energy interactions may also determine the structure of low-molecular species. The same applies for weak ligand-metal ion interactions. That both these factors may lead to intramolecular, contraction-independent equilibria between isomeric metal-ion complexes is demostrated with α-lipoic acid as ligand. This cofactor affers metal ions two different binding sites: the carboxylate group and the disulfide linkage. The carboxylate group dominates the coordinating properties of this ligand towards the biologically important metal ions, but a disulfide-metal ion interaction is still possible and under sterically favourable conditions may becomevery important; this could also be true under enzymic conditions here the carboxyl group is no longer free but amide-liked to the protein. Furthermore, due to the valeric acid side chain, the lipoyl moiety is ideally suited to undergo hydrophobic ligand-ligand interactions in mixed-ligand complexes. Such hydrophobic interactions seem to be ideal to allwe migration, e.g., of the 14 Å long lipoyllysyl moiety, and also to caciliutate the correct ‘fixation’ at the surface of the enzyme.     

Neuartige Isomeriefälle bei 1:2-CrIII- und CoIII-Komplexen von o,o'-Dihydroxyazoverbindungen: Pyramidal gebundener Stickstoff mit hoher Inversionsbarriere?

From the dimensions described in previously known X-ray structure analyses and from NMR.-spectroscopical datas of a 1:2 Co^III complex it is concluded that metal chelates of two and tri-dentated azo compounds are present in the diketo or quinone mono hydrazone form, provided that such a form is possible. As the metal atoms replaces the hydrazone proton the coordinating nitrogen atom can be predetermined. For the first time in the case of 1:2 Cr complexes from o,o'-dihydroxy azo compounds small amounts of byproducts have been observed which have the empirical composition of the main complexes. As the coordinated nitrogen atom is sp³-hybridized, its three bonds should be arranged in a pyramidal form. Therefore the ligands should be slightly bent. In the 1:2 Cr complexes where two of these ligands are coordinated to the metal atom perpendicularly to each other (Drew-Pfitzner-arrangement) 3 conformers (+ 3 mirror images) are possible. These conformers are ascribed to one group of the observed isomeric complexes. For another group it is supposed that at least one ligand is coordinated in the plane azo form. The postulated thrice bonded nitrogen atom possesses the requirements for a high inversion barrier: it is a member of two ortho condensed rings; moreover, it is bound to a Lewis acid. No such system seems to have been described, but in some published X-ray structure analyses, there is evidence to be found of its existence.     

Metal complexes of macrocyclic ligands. Part XXXIII. Effect of the side-chain length on the on/off equilibrium in the Ni2+ and Cu2+ complexes of 11-(2-aminoethyl)- and 11-(3-aminopropyl)-1,4,7,11-tetraazacyclotetradecane

Alkylation of 1,4,7-tritosyl-1,4,7,11-tetraazacyclotetradecane with CH₂O/KCN or acrylonitrile gave the corresponding cyanomethyl or 2-cyanoethyl derivatives, which, by treatment with Na in BuOH, were detosylated and reduced to the macrocyclic pentaamines 1 and 2 . The Ni²⁺ and Cu²⁺ complexes with 1 and 2 show a reversible pH-dependent change in geometry, in which the side-chain amino group is either coordinated to the metal ion (basic form) or protonated and, thus, non-coordinated (acidic form). The length of the side chain determines the log K_a values of these protonation/deprotonation equilibria: 1.89 and ～ 2.0 for the Cu²⁺ and Ni²⁺ complexes of ligand 1 with the 2-aminoethyl side chain, and 6.17 and 7.43 for the Cu²⁺ and Ni²⁺ complexes of ligand 2 with the 3-aminopropyl side chain.     

Metal Complexes with Macrocyclic Ligands. IX. Synthesis and properties of a new class of branched N4-macrocycles with an additional ligating group in the side chain

In the presence of Ni²⁺ the template reaction between 2,6-diacetylpyridine and 4-(2-dimethylaminoethyl)- or 4-(2-hydroxyethyl)-1, 7-diamino-4-azaheptane yields the complexes of either the open-chain ligand ( 3 and 11 ) or of the macrocycle ( 4 and 12 ). Reduction of the imino group in 4 and 12 with PtO₂/H₂ gives 5 and 13 , respectively. In the case of the dimethylamino derivative 5 a mixture of at least four isomers was obtained. These were partially separated by chromatography on Sephadex SP-25 cation exchanger. Through demetalation of the Ni²⁺ complexes by cyanide the new macrocycles 7 and 14 were isolated, from which the corresponding Zn²⁺ and Cu²⁺ complexes were prepared. The macrocyclic Ni²⁺-complexes 4, 12, 5 and 13 can exist in two forms depending on the pH of the solution. At low pH protonation of the dimethylamino or hydroxy group in the side chain occurs. The metal ion is then bound to the four nitrogen atoms of the macrocycle in a square planar ligand field. At higher pH, however, the dimethylamino or hydroxy group (the last one also in its deprotonated form) can coordinate to one of the axial positions, whereby pseudooctahedral coordination geometry is induced. This reaction can be quantitatively described by a reversible acid-base equilibrium, the pK_H of which greatly depends on the nature of the functional group, the degree of unsaturation of the macrocycle and the metal ion. The acid-base reaction and the concomitant structural change are a direct consequence of the unique combination of the rigid and kinetically stable structure of the macrocycle and of the flexible and kinetically labile functional group of the side chain.     

Substituent control of hydrogen bonding in palladium(II)-pyrazole complexes

Inter- and intramolecular hydrogen bonding of an N-H group in pyrazole complexes was studied using ligands with two different groups at pyrazole C-3 and C-5. At C-5, groups such as methyl, i-propyl, phenyl, or tert-butyl were present. At C-3, side chains L-CH(2)- and L-CH(2)CH(2)- (L = thioether or phosphine) ensured formation of chelates to a cis-dichloropalladium(II) fragment through side-chain atom L and the pyrazole nitrogen closest to the side chain. The significance of the ligands is that by placing a ligating side chain on a ring carbon (C-3), rather than on a ring nitrogen, the ring nitrogen not bound to the metal and its attached proton are available for hydrogen bonding. As desired, seven chelate complexes examined by X-ray diffraction all showed intramolecular hydrogen bonding between the pyrazole N-H and a chloride ligand in the cis position. In addition, however, intermolecular hydrogen bonding could be controlled by the substituent at C-5: complexes with either a methyl at C-5 or no substituent there showed significant intermolecular hydrogen bonding interactions, which were completely avoided by placing a tert-butyl group at C-5. The acidity of two complexes in acetonitrile solutions was estimated to be closer to that of pyridinium ion than those of imidazolium or triethylammonium ions.     

Coordination polymers from kinetically labile copper(I) and silver(I) complexes: true macromolecules or solution aggregates?

Copper(I) and silver(I) coordination polymers have been prepared via conversion of equimolar amounts of o‐phenanthroline‐based bis‐bidentate ligand monomers, and [Cu(CH₃CN)₄]PF₆ or AgBF₄ as the respective metal comonomers. Using NMR spectroscopy, the homogeneous constitution of the diamagnetic products has been proved, and their average chain length has been estimated to be P_n ≥ 20. Moreover, NMR studies showed the multinuclear complexes to be open (dynamic) solution aggregates when dissolved in solvents that contain coordinating species like acetonitrile or pyridine. When strictly non‐coordinating solvents are used, on the other hand, the multinuclear complexes were found to be “true” polymers, i.e. macromolecules with a constant number of repeating units per individual chain in time. At very high dilution, finally, transformation of the originally formed chain molecules into cyclic oligomers was observed when coordinating solvents are used, but not in the case of non‐coordinating solvents.     

Molecular brushes with long polyfluorene backbones and polymethacrylic acid side chains: Luminescent properties and self-organization in solutions

A series of molecular brushes with a polyfluorene (PF) backbone and polymethacrylic acid side chains of varying lengths were prepared by atom transfer radical polymerization. The structure and composition of the synthesized compounds were confirmed by ¹H NMR and IR spectroscopy. Effect of the length of the backbone on spectral and conformational parameters of the macromolecules in solutions was analyzed. The grafting density of side chains was about 90%. Spectral methods have been used to determine the dependence of side chain grafting on the luminescent properties of polymer solutions, including quantum yields. It was shown that an optimal length of polymethacrylic acid side chains provides solubility of the polymer brushes. Solutions of PF-graft-polymethacrylic acid complexes with the model substance curcumin were investigated. It was established that the molecular brushes containing curcumin form monomolecular micelles. Molecular brushes with zinc phthalocyanine, potential systems for photodynamic, and photothermal therapy, were studied.     

Light-emitting molecular machines: pH-induced intramolecular motions in a fluorescent nickel(II) scorpionate complex

A cyclam-like macrocycle has been synthesized with a pendant arm containing a dansylamide group. In the corresponding nickel(II) complex, binding of the pendant arm to the metal is pH controlled. In particular, at pH 4.3, the sulfonamide group deprotonates and coordinates the NiII center, giving rise to a complex of trigonal bipyramidal stereochemistry, as shown by X-ray diffraction studies performed on the crystalline complex salt. At pH 7.5, an OH- ion binds the metal and a six-coordinate species forms. The binding-detachment of the pendant arm to/from the NiII center is signaled by changes in the emission properties of the dansyl subunit in the side chain; the fluorescence of this side chain is high when the pendant arm is not coordinated and low when the sulfonamide group is bound to the metal. The system investigated represents the prototype of a light-emitting molecular machine, driven by a pH change.     

Careful investigation of the hydrosilylation of olefins at poly(ethylene glycol) chain ends and development of a new silyl hydride to avoid side reactions

Hydrosilylation of olefin groups at poly(ethylene glycol) chain ends catalyzed by Karstedt catalyst often results in undesired side reactions such as olefin isomerization, hydrogenation, and dehydrosilylation. Since unwanted polymers obtained by side reactions deteriorate the quality of end‐functional polymers, maximizing the hydrosilylation efficiency at polymer chain ends becomes crucial. After careful investigation of the factors that govern side reactions under various conditions, it was related that the short lifetime of the unstable Pt catalyst intermediate led to the formation of more side products under the inherently dilute conditions for polymers. Based on these results, two new chelating hydrosilylation reagents, tris(2‐methoxyethoxy)silane (5) and 2,10‐dimethyl‐3,6,9‐trioxa‐2,10‐disilaundecane (6), have been developed. It was demonstrated that the hydrosilylation efficiency at polymer chain ends was significantly increased by employing the internally coordinating hydrosilane 5. In addition, employment of the internally coordinating disilane species 6 in an addition polymerization with 1,5‐hexadiene by hydrosilylation reaction yielded a polymer with high molecular weight (M_n = 9300 g/mol), which was significantly higher than that (M_n = 2600 g/mol) of the corresponding polymer obtained with non‐chelating dihydrosilane, 1,1,3,3‐tetramethyldisiloxane. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 527–536     

Directional Dynamic Covalent Motion of a Carbonyl Walker on a Polyamine Track

Controlled directional displacement of a molecular group has been achieved based on dynamic covalent motions implementing the reactional features of the imine bond. ortho‐Carboxybenzaldehyde derivatives are able to form stable adducts with both primary and secondary amines as imines or as amino lactones, respectively, depending on the acidity of the medium. They may thus perform pH‐driven intramolecular “walking” along a non‐symmetric polyamine chain, in which an imine serves as the terminus under basic conditions on one end of the chain and a lactone formed on a secondary hydroxylamine nitrogen on the other end serves as the terminal site upon addition of acid. The displacement between the termini occurs stochastically through reversible change in valency at the carbon site of the carbonyl group between imine, aminal, iminium and amino lactone form. On the other hand, the directionality results from the stabilisation of the terminal products under given pH conditions. By its ability to undergo interconversion between C?N and O‐C‐N moieties, the ortho‐carboxybenzaldehyde group extends the realm of dynamic covalent chemistry of imines to secondary amines and opens new perspectives in this field.     

Synthesis,Structure and Noncovalent Interactions Palladium（Ⅱ）Complexes with N—Benzoyl—β—phenylalaniate Dianion and Aromatic Diimine

Two palladium(II) complexes, [Pd(bipy)(BzPhe‐N,O)] and [Pd(phen)(BzPhe‐N,O)]·4H₂O were synthesized by reactions between Pd(bipy)Cl₂ and BzPheH₂ (N‐benzoyl‐β‐phenylalanine), Pd(phen) Cl₂ and BzPheH₂ in water at pH‐9, with their structures determined by X‐ray diffraction analysis. The Pd atom is coordinated by two nitrogen atoms of bipy (or phen), the deprotonated amido type nitrogen atom and one of the carboxylic oxygens of BzPhe (BzPhe = N‐benzoyl‐β‐phenylalaninate dianion). In the complex [Pd(phen) (BzFne‐N,O)] · 4H₂O, the side chain of phenylalanine is located above and approximately parallels to the coordination plane. Both the aromatic‐aromatic stacking interaction between the phenyl ring of phenylalanine and phen, and the metal ion‐aromatic interaction between the phenyl ring of phenylalanine and Pd(II) were observed. [Pd(bipy)(BzPhe‐N,O)] has the phenylalanyl side chain oriented outwards from the coordination plane, which is mainly due to the interaction between the carbonyl oxygen atom of the amido group and the phenyl ring of phenylalanine. The reason for the different orientation of phenylalanyl side chain in the complexes was suggested.     

Controllable Intramolecular Motions That Generate Fluorescent Signals for a Metal Scorpionate Complex

Simply by changing the pH value, the side chain of complex 1 can be reversibly moved between two positions. Coordination to the metal center through the nitrogen atom of the side chain at moderate pH values is accompanied by a decrease in fluorescence intensity (from I_F=100% to I_F=60%). A further decrease is observed upon deprotonation of the bound water molecule at higher pH (I_F≤2%). Therefore, 1 can be seen as a molecular three-position switch.     

Supramolecular assembly of hydrogen bonding,ESR studies and theoretical calculations of Cu(II) complexes

A series of copper(II) complexes were synthesized by the reaction of copper(II) chlorid with 1‐phenyl‐3methyl‐(3‐dervitives phenylhydrazo)‐5‐pyrazolone (HL_n) yields 1:1 and 1:2 (M:L) complexes depending on the reaction conditions. The elemental analysis, spectral (IR, ¹H NMR, UV‐Vis and ESR), conductance and magnetic measurements were used to characterize the isolated complexes. The IR spectral data indicate that the metal ions are coordinated through the oxygen of the keto and nitrogen of hydrazone groups. The UV‐Vis spectra, magnetic moments and ESR studies indicate square planar geometry for Cu(II) complexes ( 1–3 ) by NO monobasic bidentate and the two monobasic trans bidentate in octahedral geometry for Cu(II) complexes ( 4–6 ). It is found that the change of substituent affects the theoretical calculations of Cu(II) complexes. Molecular docking was used to predict the binding between the ligands (HL_n) and the receptors of prostate cancer mutant (2Q7K), breast cancer mutant (3HB5), crystal structure of E. coli (3T88) and crystal structure of S. aureus (3Q8U). The molecular and electronic structures of Cu(II) complexes and quantum chemical calculations were studied. According to intramolecular hydrogen bond leads to increasing of the complexes stability.     

Hydrophilic graft modification of a commercial crystalline polyolefin

Hydroxy‐functionalized isotactic poly(1‐butene) was synthesized using transition metal‐catalyzed regioselective C? H borylation at the side chain of the commercial polyolefin and subsequent oxidation of the boronic ester functionality. Functionalization up to ～ 19 mol % of the termini of the ethyl side chain occurred without significant side reactions that could alter the polymer chain length. Esterification of the hydroxy group in the polymer with 2‐bromoisobutyl bromide generated a side chain‐functionalized polyolefin macroinitiator. Atom transfer radical polymerization of tert‐butyl acrylate from the macroinitiator produced a high molecular‐weight graft copolymer of the polyolefin, isotactic poly(1‐butene)‐graft‐poly(tert‐butyl acrylate) (PB‐g‐PtBA). Finally, the hydrolysis of the tert‐butoxy ester group of PB‐g‐PtBA created an amphiphilic polyolefin, isotactic poly(1‐butene)‐graft‐poly(acrylic acid), which contained a short carboxylic acid‐functionalized polymer block at the side chain. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3533–3545, 2008     

Synthesis,characterization and antimicrobial studies on metal complexes with a naphthofuran thiosemicarbazide derivatives

Complexes of the type MLCl₂, where M?=?Co(II), Cu(II), Ni(II), Zn(II), Cd(II) and Hg(II) and L is a thiosemicarbazide ligand derived from reaction between naphthofuran-2-carboxyhydrazide and p-chlorophenylisothiocynate (NCClPT)/p-bromophenylisothiocynate (NCBrPT) characterized by elemental analysis, conductance, magnetic susceptibility measurements, UV-Vis, IR, ¹H?NMR, and ESR. The thiosemicarbazide ligands are bidentate by coordinating through the oxygen of the carbonyl group and the nitrogen of the hydrazide residue. Based on the results, we propose structures for all the metal complexes. Both the ligands and their complexes have been screened for their fungicidal and bactericidal activities.     

Structures and hydration enthalpies of cationized glutamine and structural analogues in the gas phase

The structures of lithiated and sodiated glutamine, both with and without a water molecule, are investigated using experiment and theory. Loss of water from these complexes and from lithiated and sodiated complexes of asparagine methyl ester, asparagine ethyl ester, and glutamine methyl ester is probed with blackbody infrared radiative dissociation experiments performed over a wide temperature range. Threshold dissociation energies, E(o), for loss of a water molecule from these complexes are obtained from master equation modeling of these data. The values of E(o) are 63 +/- 1 and 53 +/- 1 kJ/mol for the lithiated and sodiated glutamine complexes, respectively. These values are similar to those for the nonzwitterionic model complexes and are in excellent agreement with calculated values. In contrast, water binding to the zwitterionic form is calculated to be significantly higher. These results indicate that glutamine in these lithiated and sodiated complexes with a water molecule are nonzwitterionic. Complexes with the asparagine side chain have slightly higher E(o) values than those with the glutamine side chain, a result consistent with more effective solvation of the metal ion due to the slightly longer side chain of glutamine. Calculations indicate that lithiated and sodiated glutamine are nonzwitterionic, with the metal ion interacting with the amine nitrogen and carbonyl oxygen from the amino acid backbone and the amide oxygen of the side chain. Addition of a water molecule does not affect the lowest-energy structure of lithiated glutamine, whereas, for sodiated glutamine, the lowest-energy zwitterionic and nonzwitterionic structures are essentially isoenergetic.     

Transition metal complexes of a novel quinoxaline‐based tridentate ONO donor ligand: synthesis,spectral characterization,thermal, in vitro pharmacological and molecular modeling studies

Co(II), Ni(II), Cu(II) and Zn(II) complexes of a novel tridentate heterocyclic ligand, 3‐{[(2‐benzoyl‐4‐chlorophenyl)imino]methyl}quinoxalin‐2(1H)‐one, have been synthesized. The ligand and the metal complexes were characterized using elemental analysis, molar conductance and magnetic susceptibility measurements, and UV–visible, Fourier transform infrared, ¹H NMR, ¹³C NMR, electron spin resonance and DART mass spectral data. The ligand behaves as a tridentate one, coordinating through two oxygen atoms from two keto groups and through the azomethine nitrogen atom. The thermal properties of the newly synthesized compounds were determined using thermogravimetric analysis. The ligand and its metal complexes were subjected to powder X‐ray diffraction analysis by which average crystallite size and unit cell parameters were calculated. The electrochemical behaviour of the compounds was studied using cyclic voltammetry. The ligand and the metal complexes were screened for their in vitro antimicrobial activities against the bacterial strains E. coli, K. pneumoniae, S. pneumoniae and S. aureus and the fungal species A. niger, A. flavus, P. chrysogenum and R. stolonifer. DNA binding, DNA cleavage and antioxidant activities of the compounds were also evaluated. The compounds bind with DNA through groove binding. The Cu(II) and Zn(II) complexes exhibit higher superoxide anion and hydrogen peroxide scavenging activities, respectively. The Cu(II) complex exhibits better anticancer activity against the MCF7 cell line. The compounds were subjected to molecular docking study against B‐DNA dodecamer d(CGCGAATTCGCG)₂ and vascular endothelial growth factor receptor kinase to justify the experimental DNA binding and MTT assay. Density functional theory studies were used to optimize the geometry of the compounds and to calculate the nonlinear optical properties. Copyright © 2016 John Wiley & Sons, Ltd.     

Synthesis and characterization of L‐leucine containing chiral vinyl monomer and its polymer,poly(2‐(methacryloyloxyamino)‐4‐methyl pentanoic acid)

A chiral monomer containing L ‐leucine as a pendant group was synthesized from methacryloyl chloride and L ‐leucine in presence of sodium hydroxide at 4 °C. The monomer was polymerized by free radical polymerization in propan‐2‐ol at 60 °C using 2,2′‐azobis isobutyronitrile (AIBN) as an initiator under nitrogen atmosphere. The polymer, poly(2‐(Methacryloyloxyamino)‐4‐methyl pentanoic acid) is thus obtained. The molecular weight of the polymer was determined to be: M_w is 6.9 × 10³ and M_n is 5.6 × 10³. The optical rotation of both chiral monomer and its polymer varies with the solvent polarity. The amplification of optical rotation due to transformation of monomer to polymer is associated with the ordered conformation of chiral monomer unit in the polymeric chain due to some secondary interactions like H‐bonding. The synthesized monomer and polymer exhibit intense Cotton effect at 220 nm. The conformation of the chain segments is sensitive to external stimuli, particularly the pH of the medium. In alkaline medium, the ordered chain conformation is destroyed resulting disordered random coils. The ordered coiling conformation is more firmly present on addition of HCl. The polymer exhibits swelling‐deswelling characteristics with the change of pH of the medium, which is reversible. The Cotton effect decreases linearly with the increase of temperature which is reversible on cooling. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2228–2242, 2009