Design and synthesis of site directed maleimide bifunctional chelators for technetium and rhenium

A new family of heterobifunctional linkers (L1-L9) containing a terminus consisting of a tridentate donor set for coordination of the {M(CO)(3)}(+) core (M = Tc, Re), and a thiol reactive maleimide group has been prepared conveniently and in high yield under Mitsunobu reaction conditions by the coupling of an appropriate alcohol derivative with maleimide. The rhenium complexes [Re(CO)(3)(Lx)]Br (x= 1-9) were prepared in good yields from the reactions of the ligands and (NEt(4))(2)[Re(CO)(3)Br(3)] in refluxing methanol. The ligands and their Re complexes were characterized by (1)H and (13)C NMR, IR, and ESI-MS. Ligand L4 and [Re(CO)(3)(L5)]Br have been structurally characterized by X-ray crystallography. Photoexcitation of solutions of the complexes [Re(CO)(3)(Lx)]Br (x= 4-6) gives rise to intense and prolonged luminescence at room temperature (fluorescence lifetimes of ca. 16 micros). The ligands and their Re complexes react smoothly at the maleimide linker with sulfhydryl groups of peptides and proteins at room temperature in phosphate-buffered saline (PBS, pH 7.4) to form stable thioether bioconjugates. The photoluminescence properties of the labeled conjugates are similar to those of the parent complexes, but with even longer lifetimes. The ligands can also be labeled at room temperature with (99m)Tc to give chemically robust complexes. The corresponding hydrazinonicotinamide derivative N-[5-(6'-hydrazinopyridine-3'-carbonyl)aminopentyl]maleimide (L10) was also prepared. While coupling of L10 to cysteine ethylester and synthesis of the rhenium derivative [ReCl(3)(HYNIC-maleimide)(2)] were successfully accomplished, attempts to couple [ReCl(3)(HYNIC-maleimide)(2)] to glutathione or BSA yielded intractable mixtures.     

Pyridylthiocarbazide complexes of rhenium with potential radiopharmaceutical applications

Attachment of a thioamide tethering group provides a modification of the well-known pyridylhydrazine based route to radiolabelling of biomolecules (the HYNIC system) and gives a proligand which gives stable, well-defined chelated derivatives with both Re(v) oxo and Re(III) diazenide cores. Both display previously unknown bonding modes for the pyridylthiocarbazide ligands.     

Studies directed toward the synthesis of chiral tungsten and molybdenum carbonyl complexes

A major challenge that must be met for an asymmetric intermolecular Pauson-Khand reaction is to be able to limit the possible positions on the metal complex for the organic partners. Toward this end, the synthesis of monometallic systems derived from M(CO)₆ and two bidentate ligands, in which the number of possible coordination sites is reduced to two, has been investigated.     

Conformational preferences of heteronuclear Fischer carbene complexes of cymantrene and cyclopentadienyl rhenium tricarbonyl

Homo- and heteronuclear bimetallic carbene complexes of group VII transition metals (Mn and Re), with cymantrene or cyclopentadienyl rhenium tricarbonyl as the starting synthon, have been synthesized according to classic Fischer methodology. Crystal structures of the carbene complexes with general formula [RC₅H₄ M'(CO)₂{C(OEt)(C₅H₄ M(CO)₃)}], where M = M′ = Mn, R = H (1), R = Me (2); M = Mn, M′ = Re, R = H (3); M = M′ = Re, R = H (4); and M = Re, M′ = Mn, R = H (5), are reported. A density functional theory (DFT) study was undertaken to determine natural bonding orbitals (NBOs) and conformational as well as isomeric aspects of the binuclear complexes. Application of second-order perturbation theory (SOPT) of the NBO method revealed stabilizing interactions between the methylene C–H bonds and the carbonyl ligands of the carbene metal moiety. Energy calculations in the gas phase of the cis and trans conformations of the Cp rings relative to one another are comparable, with the trans conformation slightly lower in energy. The theoretical findings have also been confirmed with single-crystal X-ray diffraction, and all solid-state structures are found in the trans geometry.     

Synthesis and catalytic activity of monobridged bis(cyclopentadienyl)rhenium carbonyl complexes

Thermal treatment of three monobridged biscyclopentadienes (C₅H₅)R(C₅H₅) [R = C(CH₃)₂ (1), C(CH₂)₅ (2), Si(CH₃)₂ (3)] with Re₂(CO)₁₀ in refluxing mesitylene gave the corresponding complexes [(η ⁵-C₅H₄)₂R][Re(CO)₃]₂ [R = C(CH₃)₂ (4), C(C₅H₁₀) (5), Si(CH₃)₂ (6)], which were separated by chromatography, and characterized by elemental analysis, IR, and ¹H NMR spectroscopy. The molecular structures of complexes 5 and 6 were characterized by X-ray crystal diffraction analysis and show that both are monobridged bis(cyclopentadienyl)rhenium carbonyl complexes in which the molecule consists of two [(η ⁵-C₅H₄)Re(CO)₃] moieties linked by a single bridge, in which each of the two Re(CO)₃ units is coordinated to the cyclopentadienyl ring in an η ⁵ mode. All three of these monobridged bis(cyclopentadienyl)rhenium carbonyl complexes have good catalytic activities in Friedel–Crafts alkylation reactions.     

Reactivity of molybdenum and rhenium hydroxo-carbonyl complexes toward organic electrophiles

The hydroxo compounds [Re(OH)(CO)(3)(N-N)] (N-N=bipy, 2 a; Me(2)-bipy, 2 b) were prepared in a biphasic H(2)O/CH(2)Cl(2) medium by reaction of [Re(OTf)(CO)(3)(N-N)] with KOH. In contrast, when anhydrous CH(2)Cl(2) was used, the binuclear hydroxo-bridged compound [[Re(CO)(3)(bipy)](2)(mu-OH)]OTf (3-OTf) was obtained. Compound [Re(OH)(CO)(3)(Me(2)-bipy)] (2 b) reacted with phenyl acetate or vinyl acetate to afford [Re(OAc)(CO)(3)(Me(2)-bipy)] (4) and phenol or acetaldehyde, respectively. The reactions of [Mo(OH)(eta(3)-C(3)H(4)-Me-2)(CO)(2)(phen)] (1), 2 a, and 2 b toward several unsaturated organic electrophiles were studied. The reaction of 1 with (p-tolyl)isocyanate afforded an adduct of N,N'-di(p-tolyl)urea and the carbonato-bridged compound [[Mo(eta(3)-C(3)H(4)-Me-2)(CO)(2)(phen)](2)(mu-eta(1)(O),eta(1)(O)-CO(3))] (5). In contrast, the reaction of 2 a with phenylisocyanate afforded [Re(OC(O)NHPh)(CO)(3)(bipy)] (6); this results from formal PhNCO insertion into the O-H bond. On the other hand, compounds [Mo[SC(O)NH(p-tolyl)](eta(3)-C(3)H(4)-Me-2)(CO)(2)(phen)] (7), [Re[SC(O)NH(p-tolyl)](CO)(3)(Me(2)-bipy)] (8 a), and [Re[SC(O)NHEt](CO)(3)(Me(2)-bipy)] (8 b) were obtained by reaction of 1 or 2 b with the corresponding alkyl or aryl isothiocyanates. In those cases, RNCS was inserted into the M-O bond. The reactions of 1, 2 a, and 2 b with dimethylacetylenedicarboxylate (DMAD) gave the complexes [Mo[C(OH)-C(CO(2)Me)C(CO(2)Me)-O](eta(3)-C(3)H(4)-Me-2)(CO)(phen)] (9) and [Re[C(OH)C(CO(2)Me)C(CO(2)Me)O](CO)(2)(N-N)] (N-N=bipy, 10 a; Me(2)-bipy, 10 b). The molecules of these compounds contain five-membered metallacycles that are the result of coupling between the hydroxo ligand, DMAD, and one of the CO ligands. The new compounds were characterized by a combination of IR and NMR spectroscopy, and for [[Re(CO)(3)(bipy)(2)(mu-OH)]BF(4) (3-BF(4)), 4, 5, 6, 7, 8 b, 9, and 10 b, also by means of single-crystal X-ray diffraction.     

Comparative electrochemistry of technetium(V) and rhenium(V) dioxo complexes

The heavy use of^99mTc in nuclear medicine and the recent development of¹⁸⁸Re radiopharmaceuticals have encouraged the comparative study of Tc and Re coordination compounds. In this work, the electrochemistry of [M^VO₂ (amine)₂]⁺ (M=Tc, Re; amine = ethylenediamine, 1,3-diaminopropane, diethylenetriamine, triethylenetetramine) complexes is studied by cyclic voltammetry and the results are compared. The voltammograms of these compounds, obtained at different pH values, show that [ReO₂(amine)₂]⁺ cations are thermodynamically stable even when protonated. On the other hand, analogous Tc compounds are not so stable and easily decompose if existing as [TcO(OH) (amine)₂]²⁺.     

Chemical reactivity of analogous technetium(V) and rhenium(V) dioxo complexes

All complexes of the series [MO₂L₂]⁺ (M=Tc, Re; L=ethylenediamine (en), 1,3-diaminopropane (1,3-dap)) have been synthesized and their chemical reactivities investigated. The following properties were studied: stability of the aqueous solutions at different pH values, substitution kinetics, lipophilicity and protein binding. The complexes show very similar reactivity in aqueous solution. From a radiopharmaceutical point of view, no significant difference in their in vivo behavior is expected.     

Tricarbonyl complexes of rhenium(I) and technetium(I) with thiourea derivatives

fac-[M(CO)₃X₃]²⁻ complexes (M=Re, X=Br; M=Tc, X=Cl) react with thiourea derivatives under formation of stable rhenium(I) and technetium(I) complexes. The composition of the products can be controlled by the steric requirements of the ligands and their ability to form chelates.The products of reactions with tetramethylthiourea, Me₄tu (I), N,N-diethylthiocarbamoylbenzamidine, H₂Et₂tcb (II), and morpholinylthiocarbamoylbenzamidine, H₂morphtcb (III), have been studied by X-ray crystallography showing that the products belong to three different structural types. A mononuclear complex of the composition fac-[Re(CO)₃Br(Me₄tu)₂] has been isolated with tetramethylthiourea, whereas the thiocarbamoylbenzamidines deprotonate and act as N,S-chelating ligands. This results in the formation of a dimeric [Tc(CO)₃(HEt₂tcb-N,S)]₂ complex with a central, almost square Tc₂S₂ unit and a monomeric compound of the composition [Tc(CO)₃(Hmorphtcb-N,S)(H₂morphtcb-S)]. The latter compound contains a neutral, S-bonded morpholinylthiocarbamoylbenzamidine in the unusual imine form in addition to a chelate-bonded Hmorphtcb⁻ ligand.     

Aryl and NHC compounds of technetium and rhenium

Air- and water-stable phenyl complexes with nitridotechnetium(V) cores can be prepared by straightforward procedures. [TcNPh(2)(PPh(3))(2)] is formed by the reaction of [TcNCl(2)(PPh(3))(2)] with PhLi. The analogous N-heterocyclic carbene (NHC) compound [TcNPh(2)(HL(Ph))(2)], where HL(Ph) is 1,3,4-triphenyl-1,2,4-triazol-5-ylidene, is available from (NBu(4))[TcNCl(4)] and HL(Ph) or its methoxo-protected form. The latter compound allows the comparison of different Tc-C bonds within one compound. Surprisingly, the Tc chemistry with such NHCs does not resemble that of corresponding Re complexes, where CH activation and orthometalation dominate.     

Aqueous phase carbon dioxide and bicarbonate hydrogenation catalyzed by cyclopentadienyl ruthenium complexes

The water‐soluble ruthenium(II) complexes [Cp′RuX(PTA)₂]Y and [CpRuCl(PPh₃)(mPTA)]OTf (Cp′ = Cp, Cp*, X = Cl and Y = nil; or X = MeCN and Y = PF₆; PTA = 1,3,5‐triaza‐7‐phosphaadamantane; mPTA = 1‐methyl‐1,3,5‐triaza‐7‐phosphaadamantane) were used as catalyst precursors for the hydrogenation of CO₂ and bicarbonate in aqueous solutions, in the absence of amines or other additives, under relatively mild conditions (100 bar H₂, 30–80 °C), with moderate activities. Kinetic studies showed that the hydrogenation of HCO₃^? proceeds without an induction period, and that the rate strongly depends on the pH of the reaction medium. High‐pressure multinuclear NMR spectroscopy revealed that the ruthenium(II) chloride precursors are quantitatively converted into the corresponding hydrides under H₂ pressure. Copyright © 2007 John Wiley & Sons, Ltd.     

Combinatorial synthesis of benzimidazolium dyes and its diversity directed application toward GTP-selective fluorescent chemosensors

Highly selective fluorescence turn-on GTP sensor, GTP Green, was discovered by a diversity directed sensor approach, combined by solid-phase combinatorial synthesis of a benzimidazolium library and high-throughput screening.     

烯基取代环戊二烯基钌配合物的合成及晶体结构

本文通过环戊二烯基钠(茂钠)与溴丙烯反应制得单取代的环戊二烯,茂钠与氯丙烯得到双取代的环戊二烯。利用这两个配体合成了烯基取代的环戊二烯基(双三苯膦)氯化钌(1,2)并对化合物(2)进行了晶体结构分析。     

Efforts directed toward the synthesis of colchicine: application of palladium-catalyzed siloxane cross-coupling methodology

[reaction: see text] Colchicine is an important and synthetically challenging natural product. The key synthetic step in this approach to the synthesis of colchicine involved a palladium-catalyzed cross-coupling reaction between 5-bromotropolone (4) and an aryl siloxane to form the aryl-tropolone bond. The coupling of a variety of highly functionalized aryl siloxane derivatives was investigated and optimized coupling conditions were developed. It was discovered that a palladium catalyst with a high degree of phosphine ligand coordination (5 equiv of phosphine/mol Pd) was necessary to efficiently couple aryl siloxanes with 5-bromotropolone (4). In addition, the coupling approach has provided a direct comparison between siloxane and boronic acid coupling technologies that demonstrated that aryl siloxanes and boronic acids produce similar yields of highly functionalized biaryl products.     

Studies directed toward the synthesis of the massileunicellins

An approach to the massileunicellins is described that employs a cycloaldol reaction to assemble the isobenzofuran bicyclic core. A stereoselective rearrangement-epoxidation-oxidation cascade and a chelation controlled addition to a hindered acyl furan are used to install the C3, C11, C12, and C13 oxygens. The synthesis establishes eight of the nine stereocenters present in the isobenzofuran core of the massileunicellins.