Group Transfer Reactions Research Articles

Ultraviolet Laser Induced Hydrogen Transfer Reaction: Study of the First Step of MALDI In-Source Decay Mass Spectrometry

The early mechanisms of matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) are described herein. MALDI-ISD is initiated by the hydrogen transfer from excited matrix molecules to the carbonyl oxygen of the peptide backbone, which is followed by a radical-induced cleavage, producing the c'/z• fragment pair. As expected, the use of 2,5-DHB or 1,5-DAN was efficient to induce MALDI-ISD, and the strongest intensity of MALDI-ISD fragments was observed when laser shots were performed on matrix crystals. In contrast, the hydrogen radical transfer reaction was suppressed by using ionic liquid and amorphous structure of 2,5-DHB and 1,5-DAN mixture as a matrix. Our results suggest that the hydrogen transfer occurs on the matrix crystal during the dissipation of the laser energy and before desorption, following ISD fragments formed in the MALDI plume.

The Photolysis of Disulfide Bonds in IgG1 and IgG2 Leads to Selective Intramolecular Hydrogen Transfer Reactions of Cysteine Thiyl Radicals, Probed by Covalent H/D Exchange and RPLC-MS/MS analysis

The evaluation of photo-instability of biotherapeutic products is mandated by regulatory agencies. Photo-irradiation can induce oxidative modifications in proteins, which may lead to undesired biological and therapeutic consequences. Among the modifications, epimerization of amino acid residues can occur upon photo-irradiation of IgGs. We show here, that UV irradiation (λ = 253.7nm) of IgG1 and IgG2 leads to the formation of intermediary carbon-centered radicals, validated by covalent incorporation of deuterium into the protein primary sequence. By MS/MS analysis we identified the sites of deuterium incorporation, such as the sequence QD [303:304, HC], present in the peptide of VVSVLTVVHQDWLNGK [294:309, HC] in both IgG1 and IgG2, and V [111, LC] and K [116, LC], present in the peptide VTVLGQPK [109:116, LC] in IgG2. Both peptides are in the proximity of intrachain disulfide bonds. The exposure of IgG1 and IgG2 to UV-light (λ = 253.7nm) generates specific carbon-centered radicals. The latter were evidenced by a covalent H-D exchange reaction that likely occurred through a hydrogen atom transfer reaction between cysteine thiyl radical and C-H bond.

Reaction mechanisms: pericyclic reactions

This is a review of forty five articles on pericyclic reactions published in 2012. Reviewed here are cycloadditions ([2+2], [3+2], [4+2], [4+3], [5+2], and [8+2]), sigmatropic reactions ([1,5]-, [2,3]-, [3,3]-, and [3,5]-shifts), as well as group transfer reactions, dyotropic rearrangements, cycloaromatization, and cascade reactions. Many of these pericyclic reactions were purely “organic”, while some eight used metal catalysts.

Group transfer reactions of d0 transition metal complexes: redox-active ligands provide a mechanism for expanded reactivity

Group- and atom-transfer is an attractive reaction class for the preparation of value-added organic substrates. Despite a wide variety of known early-transition metal oxo and imido complexes, these species have received limited attention for atom- and group-transfer reactions, owing to the lack of an accessible metal-based two-electron redox couple. Recently it has been shown that redox-active ligands can support the multi-electron changes required to promote group-transfer reactivity, opening up new avenues for group- and atom-transfer catalyst design. This Perspective article provides an overview of group transfer reactivity in early-transition metal complexes supported by traditional ligand platforms, followed by recent advances in the atom- and group-transfer reactivity of d(0) metal complexes containing redox-active ligands.

ChemInform Abstract: Practical Iron‐Catalyzed Atom/Group Transfer and Insertion Reactions

AbstractReview: 86 refs.

The European Young Chemist Award 2012

The European Young Chemist Award 2012

DFT and ab initio study on mechanism of olefin hydroalumination by XAlBui2 in the presence of Cp2ZrCl2 catalyst. III. Efficiency of transmetallation in Cp2ZrRCl–XAlBui2 system

Transmetallation leading to formation of n-Pr–Al bond in the Cp2Zr(n-Pr)Cl–XAlBui2 (X = H, Cl, Bui) couple was studied using PBEPBE/3ζ and RI-MP2/Λ2//PBEPBE/3ζ approaches. Calculation results were corrected by taking into account of nonspecific solvent effect (toluene). Depending on the nature of organoaluminum compound, either decomposition of alkylalane self-associates (HAlBui2 and ClAlBui2 cases) or alkyl group transfer reaction from Zr to Al atom (AlBui3 case) could be a rate-determining step of the process. The modeling of kinetics with calculated Gibbs free energies for elementary steps of the process shows that transmetallation rates decrease in the following order: ClAlBui2 > HAlBui2 >> AlBui3.

Redox Routes to Substitution of Aluminum(III): Synthesis and Characterization of (IP–)2AlX (IP = α-iminopyridine, X = Cl, Me, SMe, S2CNMe2, C≡CPh, N3, SPh, NHPh)

Redox active ligands are shown to facilitate a variety of group transfer reactions at redox inert aluminum(III). Disulfides can be used as a two-electron group transfer reagent, and we show that (IP(-))(2)AlSR can be formed by reaction of [(THF)(6)Na][(IP(2-))(2)Al] (1c) with disulfides RSSR (where X = C(S)NMe(2), 4; SMe, 5). In a more general redox route to substitution of aluminum bis(iminopyridine) complexes, we report zinc(II) salts as a group transfer reagent. Reaction of [((R)IP(2-))(2)Al](-) (R = H, 1c; Me, 1d) with ZnX(2) affords ((R)IP(-))(2)AlX (where IP = iminopyridine, R = H, and X = Cl, 2; CCPh, 6; N(3), 7; SPh, 8; or R = Me and X = NHPh, 9). Single crystal X-ray diffraction analysis of the complexes reveal that each of the five coordinate complexes reported here has a trigonal bipyramidal geometry with τ = 0.668 - 0.858. We observed a correlation between the greatest deviations from ideal trigonal bipyramidal symmetry (lowest τ values), the bond lengths consistent with smallest degree of ligand reduction, and the least polarizable X ligand in (IP(-))(2)AlX. Complex 4 is six-coordinate and is best described as distorted octahedral. Variable temperature magnetic susceptibility measurements indicate that each of the complexes 3-9 has a biradical electronic structure similar to previously reported 2. Magnetic exchange coupling constants in the range J = -94 to -212 cm(-1) were fit to the data for 2-9 to describe the energy of antiferromagnetic interaction between ligand radicals assuming a spin Hamiltonian of the form Ĥ = -2JŜ(L(1))·Ŝ(L(2)). The strongest coupling occurs when the angle between the ligand planes is smallest, presumably to afford good overlap with the Al-X σ* orbital. Electrochemical properties of the complexes were probed using cyclic voltammetry and each of 3-9 displayed a reversible two-electron reduction and two quasi-reversible one-electron oxidation processes. The energy of the ligand based redox processes for 2-9 differ by about 150 mV over all complexes and show a correlation with the degree of IP(-) reduction observed crystallographically; more reduced IP(-) ligands require higher potentials for further reduction. Comproportionation constants that describe the equilibrium for the reaction (IP(-))(2)AlX + (IP)(2)AlX ↔ (IP(-))(IP)AlX fall in the range of K(c) = 10(5.7) to 10(7.9) for 3-9.

Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine–cysteine peptides in solution

Experimental studies in hemeproteins and model Tyr/Cys-containing peptides exposed to oxidizing and nitrating species suggest that intramolecular electron transfer (IET) between tyrosyl radicals (Tyr-O) and Cys residues controls oxidative modification yields. The molecular basis of this IET process is not sufficiently understood with structural atomic detail. Herein, we analyzed using molecular dynamics and quantum mechanics-based computational calculations, mechanistic possibilities for the radical transfer reaction in Tyr/Cys-containing peptides in solution and correlated them with existing experimental data. Our results support that Tyr-O to Cys radical transfer is mediated by an acid/base equilibrium that involves deprotonation of Cys to form the thiolate, followed by a likely rate-limiting transfer process to yield cysteinyl radical and a Tyr phenolate; proton uptake by Tyr completes the reaction. Both, the pKa values of the Tyr phenol and Cys thiol groups and the energetic and kinetics of the reversible IET are revealed as key physico-chemical factors. The proposed mechanism constitutes a case of sequential, acid/base equilibrium-dependent and solvent-mediated, proton-coupled electron transfer and explains the dependency of oxidative yields in Tyr/Cys peptides as a function of the number of alanine spacers. These findings contribute to explain oxidative modifications in proteins that contain sequence and/or spatially close Tyr–Cys residues.

Mapping the tRNA Binding Site on the Surface of Human DNMT2 Methyltransferase

The DNMT2 enzyme methylates tRNA-Asp at position C38. Because there is no tRNA-Dnmt2 cocrystal structure available, we have mapped the tRNA binding site of DNMT2 by systematically mutating surface-exposed lysine and arginine residues to alanine and studying the tRNA methylation activity and binding of the corresponding variants. After mutating 20 lysine and arginine residues, we identified eight of them that caused large (>4-fold) decreases in catalytic activity. These residues cluster within and next to a surface cleft in the protein, which is large enough to accommodate the tRNA anticodon loop and stem. This cleft is located next to the binding pocket for the cofactor S-adenosyl-L-methionine, and the catalytic residues of DNMT2 are positioned at its walls or bottom. Many of the variants with strongly reduced catalytic activity showed only a weak loss of tRNA binding or even bound better to tRNA than wild-type DNMT2, which suggests that the enzyme induces some conformational changes in the tRNA in the transition state of the methyl group transfer reaction. Manual placement of tRNA into the structure suggests that DNMT2 mainly interacts with the anticodon stem and loop.

Practical iron-catalyzed atom/group transfer and insertion reactions

Iron-catalyzed reactions are receiving a surge of interest owing to the natural abundance and biocompatibility of Fe and the urge to develop practically useful sustainable catalysis for fine chemical industries. This article is a brief account of our studies on the C–O and C–N bond formation reactions catalyzed by Fe complexes supported by oligopyridine, macrocyclic tetraaza, and fluorinated porphyrin ligands. The working principle is the in situ generation of reactive Fe=O and Fe=NR intermediates supported by these oxidatively robust N-donor ligands for oxygen atom/nitrogen group transfer and insertion reactions. The catalytic reactions include C–H bond oxidation of saturated hydrocarbons (up to 87 % yield), epoxidation of alkenes (up to 96 % yield), cis-dihydroxylation of alkenes (up to 99 % yield), epoxidation–isomerization (E–I) reaction of aryl alkenes (up to 94 % yield), amination of C–H bonds (up to 95 % yield), aziridination of alkenes (up to 95 % yield), sulfimidation of sulfides (up to 96 % yield), and amide formation from aldehydes (up to 89 % yield). Many of these catalytic reactions feature high regio- and diastereoselectivity and/or high product yields and substrate conversions, and recyclability of the catalyst, demonstrating the applicability of Fe-catalyzed oxidative organic transformation reactions in practical organic synthesis.

Axial Functionalization of Sterically Hindered Titanium Phthalocyanines

Several axially functionalized, weakly aggregating titanium phthalocyanines (Pc) have been synthesized and characterized. Soluble titanium dichlorido tetrakis-(1,1,4,4-tetramethyl-6,7-tetralino)-porphyrazine [Pc(#)TiCl(2)] (5) has been prepared by reductive cyclotetramerization of the respective dinitrile precursor in the presence of TiCl(4). 5 and the analogous oxido compound [Pc(#)TiO] (1) are versatile starting materials for the formation of other axially functionalized titanium phthalocyanines such as organoimido (6, 7), alkoxido and aryloxido (8, 9), peroxido (10), sulfido (12), disulfido (11), selenido (14) or diselenido (13) species. Furthermore the deprotonated ligand salts [Pc(#)M(2)] (M = Li (2), Na (3), K (4) are described. The reactivity of the titanium compounds was studied in atom group transfer reactions and ethene polymerization. The crystal structures of 5 and the free ligand Pc(#)H(2) are reported. 5 crystallizes from dichloromethane in the cubic space group Im3. The two chlorido ligands exhibit a cis arrangement. The free ligand Pc(#)H(2) crystallizes in the trigonal space group R3.

Attachment of carbonyl functionalities onto olefins via copper-promoted radical reaction of dichloromethylcyanides

Chemo- and regioselective protocols for attachment of various carbonyl functionalities onto unactivated olefins have been developed. Atom transfer radical reactions of Cl3CCN, Cl2C(R)CN, and Cl2C(CN)2 were all promoted efficiently by a catalytic amount of CuCl and 1,1′-bis(diphenylphosphino)ferrocene to introduce chloromethylcyanide and chloride units to the C–C double bonds. Conversion of the chloromethylcyanide to the carbonyl functionalities (e.g., aldehydes, ketones and esters), and subsequent double bond reconstruction through elimination of HCl resulted in selective formation of the carbonyl-conjugated E-olefins.

Synthesis and characterization of polylimonene: Polymer of an optically active terpene

AbstractRadical polymerization of limonene (limonene) using benzoyl peroxide (BPO) as an initiator at 85°C ± 1°C under an inert atmosphere of nitrogen in xylene as solvent was carried out. The system follows nonideal kinetics: Rp α [I]0.3 [M]1.4, due to both primary radical termination and degradative chain transfer reaction. The activation energy of the polymerization was estimated to be 22.97 kJ mol−1. 1H‐NMR spectrum of polymer shows the presence of a triplet between 2 and 2.5 δ, which reveals that β‐carbon of limonene is the active site in the polymerization of limonene. The FTIR spectrum of the polymer shows band at 1645 cm−1 due to gem disubstituted CC stretching vibrations. The glass transition temperature (Tg) of the polylimonene of the polylimonene is 116°C. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Catalytic conversion of compounds representative of lignin-derived bio-oils: a reaction network for guaiacol, anisole, 4-methylanisole, and cyclohexanone conversion catalysed by Pt/γ-Al2O3

The conversion of compounds representative of lignin and lignin-derived bio-oils (guaiacol, anisole, 4-methylanisole, and cyclohexanone), catalysed by Pt/Al2O3 in the presence of H2 at 573 K is described by a reaction network indicating a high selectivity for platinum-catalysed aromatic carbon–oxygen bond cleavage accompanied by acid-catalysed methyl group transfer reactions.

Radical-mediated reduction of the dithiocarbamate group under tin-free conditions

Reductive desulfurisation of dithiocarbamates is conveniently achieved using H(3)PO(2)-Et(3)N-ACCN in refluxing dioxane. Fused and spirocyclic β-lactams, prepared through 4-exo trig carbamoyl radical cyclisation-dithiocarbamate group transfer reactions, are reduced without fragmentation of the strained 4-membered ring. Diethyl tetraacetyl-d-glucopyranosyl dithiocarbamate is selectively reduced with or without acyloxy group migration depending on reaction conditions and choice of reductant. Deuterium incorporation from D(3)PO(2)-Et(3)N is observed for a system involving a nucleophilic radical intermediate, but not in the case of the electrophilic radical obtained through acyloxy group migration on a glucose derivative.

Possible role of Mg2+ ion in the reaction of organophosphate (dichlorvos) with serine

▸Proposed mechanism for catalytic role of magnesium ion in nucleophic attack of serine to DDVP. ▸Magnesium reduces the pKa of serine hydroxyl group and favors the reaction of serine with DDVP. ▸It is proposed that magnesium acts through a ion radical mechanism. Abstract Organophosphate pesticides (OPs) inhibit both true and pseudo-cholinesterases by reaction with the hydroxyl group of serine in their active sites. Poisoning with OPs is commonly seen in clinics. A common antidote for OP poisoning is atropine but, after ageing and OP dealkylation, even oximes could not be effective. It has been shown that oximes are not always useful in management of OP poisoning. On the other hand, magnesium has been found effective in both clinical and experimental studies. Studies to find more effective antidotes for OP poisoning are in progress. Presently, the possible role of magnesium ion in catalysis of reaction of dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP), a water-soluble OP, with serine is proposed. The hydroxyl group of serine could be a target to which DDVP can react. Nucleophilic attack of pralidoxime to DDVP was previously investigated. To confirm the idea, data were derived from recent and previous research on the role of magnesium in phosphoryl group transfer reactions. Possible reactions of serine and pralidoxime with DDVP in the absence and the presence of magnesium ion were separately investigated theoretically. We propose that the chemical reaction of serine with DDVP exclusively occurs in the presence of a magnesium divalent cation, whereas the reaction of pralidoxime with DDVP occurs independent of the presence of the magnesium ion. The role of the dissociation constant (p K a ) of functional groups in these reactions seems important. It is suggested that application of serine in combination with the magnesium cation can become a more efficient antidote for treatment of OP poisoning.

Congested C2-symmetric aryliodanes based on an anti-dimethanoanthracene backbone

A family of congested aryliodanes based on an anti-dimethanoanthracene backbone has been synthesised and two diaryliodonium salts and the iodyl derivative characterised by X-ray analysis. The latter shows a rare water coordination to the iodine(V) centre in the solid state. Applications of these reagents in functional group transfer reactions are reported.

Retracing the evolution of monometallic ruthenium–arene catalysts for C–C bond formation

Preformed or in situ generated monometallic ruthenium-arene complexes with the generic formula RuX(2)(arene)(L) (L = phosphine or N-heterocyclic carbene) are versatile and efficient catalyst precursors for olefin metathesis and atom transfer radical reactions. Their synthesis is usually accomplished using simple and straightforward experimental procedures starting from the [RuCl(2)(p-cymene)](2) dimer. This article retraces their evolution over the past 20 years and highlights similarities and differences with the parallel development of well-defined RuX(2)(=CHR)(L(1))(L(2)) ruthenium-alkylidene catalysts.

ChemInform Abstract: Synthesis and Catalytic Properties of 4‐Aryl‐2,3‐dihydro‐4H‐pyrimido[2,3‐b]benzothiazoles for Asymmetric Acyl or Carboxyl Group Transfer Reactions.

AbstractSome chiral dihydropyrimidobenzothiazoles are prepared by condensation of 2‐aminobenzothiazoles with HCHO and styrenes and subsequent optical resolution.