Cu(I)-Catalyzed Intramolecular Cyclization of Alkynoic Acids in Aqueous Media: A “Click Side Reaction”

Alkynoic acids, in particular, 4-pentynoic acid derivatives, undergo intramolecular cyclizations to enol lactones under reaction conditions typically applied for the Cu(I)-catalyzed cycloaddition of terminal alkynes and azides (click chemistry). Starting from appropriate alkynoic acid derivatives, either enol lactones or 1,2,3-triazole click products can be obtained selectively by Cu(I) catalysis in aqueous media

Versatile Routes to C-2- and C-6-Functionalized Glucose Derivatives of Iminodiacetic Acid

A series of novel d-glucose derivatives, functionalized at the C-2 or the C-6 position with an iminodiacetic acid moiety for transition-metal complexation, has been prepared. The sugar and the metal-chelating parts are separated by either propyl or octyl chains and were introduced by the reaction of bromoalkylamine. Either N-1-Boc-3-bromopropylamine (17) or N-(8-bromooctyl)phthalimide (19) reacted with methyl 3,5,6-tri-O-benzyl-α-β-d-glucofuranoside (4) (C-2 position) and 1,2:3,5-(O-methylene)-α-d-glucose (11) (C-6 position), respectively, in the presence of sodium hydride in DMF at room temperature, affording the desired intermediates. For aminopropyl derivatives, yields varied between 57% and 65%, and for aminooctyl derivatives, yields varied between 40% and 71%. After deprotection of the amine functionality, the metal chelate was built up by dialkylation (6a−c and 13a,b) with methyl bromoacetate in the presence of triethylamine under reflux in THF. Yields varied between 56% and 69% for the glucose modified at the C-2 position and between 58% and 62% for the one modified at the C-6 position. All compounds were characterized by 1H or 13C NMR or both, IR, and mass spectroscopy. Final products were isolated as a mixture of α and β anomers

Additional file 1: of Comparison of desferrioxamine and NODAGA for the gallium-68 labeling of exendin-4

Figure S1. Schematic representation of the peptides investigated in the study. Figure S2. RP-HPLC chromatograph of [68Ga]Ga-Ex4NOD (top) and [68Ga]Ga-Ex4DFO (bottom). Figure S3. Mass spectrometric analysis of [natGa]Ga-Ex4NOD. Figure S4. Mass spectrometric analysis of [natGa]Ga-Ex4DFO. (DOCX 812 kb

Organometallic [Re(CO)₃]⁺ and [Re(CO)₂(NO)]²⁺ Labeled Substrates for Human Thymidine Kinase 1

Thymidine was functionalized at position N3 with a tridentate iminodiacetic acid chelating system and a potentially tetradentate mercaptoethyliminodiacetic acid chelating system. Spacers of different lengths (ethyl and butyl) were introduced between the chelators and thymidine. The derivatives were labeled with the [Re(CO)2(NO)]2+ and [Re(CO)3]+ cores to give isostructural complexes with different overall charges. All complexes were analyzed by NMR, MS, and IR, and in addition, the X-ray structure of a [Re(CO)2(NO)]2+ labeled thymidine derivative functionalized at the N3 position was solved. The ligands incorporating the potentially tetradentate mercaptoethyliminodiacetic acid chelating system coordinated tridentately through iminodiacetic acid to both the [Re(CO)2(NO)]2+ core and the [Re(CO)3]+ core. This was surprising given that the reaction of [NEt4][Re(CO)2(NO)Br3] with the model ligand ethylmercaptoethyliminodiacetic acid led to dissociation of a carbonyl ligand and formation of a monocarbonyl−mononitrosyl complex, as confirmed by X-ray structure analysis. All of the organometallic thymidine derivatives were substrates for human thymidine kinase 1, a key enzyme in (cancer) cell proliferation. Neutral [Re(CO)2(NO)]2+ labeled thymidine derivatives revealed substrate activity ranging from 24 to 40%, and the structurally analogous anionic [Re(CO)3]+ labeled thymidine derivatives from 20 to 38% compared with the natural substrate thymidine

Organometallic [Re(CO)₃]⁺ and [Re(CO)₂(NO)]²⁺ Labeled Substrates for Human Thymidine Kinase 1

Thymidine was functionalized at position N3 with a tridentate iminodiacetic acid chelating system and a potentially tetradentate mercaptoethyliminodiacetic acid chelating system. Spacers of different lengths (ethyl and butyl) were introduced between the chelators and thymidine. The derivatives were labeled with the [Re(CO)2(NO)]2+ and [Re(CO)3]+ cores to give isostructural complexes with different overall charges. All complexes were analyzed by NMR, MS, and IR, and in addition, the X-ray structure of a [Re(CO)2(NO)]2+ labeled thymidine derivative functionalized at the N3 position was solved. The ligands incorporating the potentially tetradentate mercaptoethyliminodiacetic acid chelating system coordinated tridentately through iminodiacetic acid to both the [Re(CO)2(NO)]2+ core and the [Re(CO)3]+ core. This was surprising given that the reaction of [NEt4][Re(CO)2(NO)Br3] with the model ligand ethylmercaptoethyliminodiacetic acid led to dissociation of a carbonyl ligand and formation of a monocarbonyl−mononitrosyl complex, as confirmed by X-ray structure analysis. All of the organometallic thymidine derivatives were substrates for human thymidine kinase 1, a key enzyme in (cancer) cell proliferation. Neutral [Re(CO)2(NO)]2+ labeled thymidine derivatives revealed substrate activity ranging from 24 to 40%, and the structurally analogous anionic [Re(CO)3]+ labeled thymidine derivatives from 20 to 38% compared with the natural substrate thymidine

Comparative Studies of Substitution Reactions of Rhenium(I) Dicarbonyl−Nitrosyl and Tricarbonyl Complexes in Aqueous Media

The ligand substitution behavior of [ReBr3(CO)3](NEt4)2 (1) and [ReBr3(CO)2(NO)]NEt4 (2) in aqueous media was compared. Ligand exchange reactions were performed with multidentate chelating systems such as picolylaminediacetic acid (L1; N,N‘,O,O‘), nitrilotriacetic acid (L2; N,O,O‘,O‘ ‘), iminodiacetic acid (L3; N,O,O‘), and bis(2-pyridyl)methane (L4; N,N‘). The products of the substitution reactions were isolated and characterized by means of IR, NMR, MS, and X-ray structure analysis. NMR and crystallographic analyses confirmed the formation of single structural isomers in all cases with a ligand-to-metal ratio of 1:1. With ligands L1 and L2 and precursor 1 the tridentately coordinated complexes [Re(L1)(CO)3] (7) and [Re(L2)(CO)3]2- (8) were formed. With precursor 2 the same ligands unexpectedly coordinated tetradentately after displacing a CO ligand, yielding complexes [Re(L1)(CO)(NO)] (3) and [Re(L2)(CO)(NO)]- (4). In both complexes NO was found to be coordinated trans to the carboxylate group. Time-dependent IR spectra of the reaction of 2 with ligand L1 and L2 confirmed the loss of one CO during the reaction. The product of the reaction of 2 with L3 was identified as the neutral complex [Re(L3)(CO)2(NO)] (5), again, with the nitrosyl coordinated trans to the carboxylate. With 1, ligand L3 formed the anionic complex [Re(L3)(CO)3]- (9). Finally the reactions with L4 yielded the complexes [ReBr(L4)(CO)2(NO)]Br (6) and [ReBr(L4)(CO)3] (10), in which bromide was found to be coordinated trans to the NO and CO, respectively. The X-ray structures of 3, 5−7, and 10 are discussed:  3, monoclinic P21/n, with a = 14.607(1) Å, b = 8.057(1) Å, c = 24.721(1) Å, β = 107.117(5)°, and Z = 4; 5, triclinic P1̄, with a = 6.909(1) Å, b = 9.882(1) Å, c = 14.283(1) Å, α = 89.246(9)°, β = 89.420(9)°, γ = 86.196(9)°, and Z = 4; 6, triclinic P1̄, with a = 9.823(1) Å, b = 10.094(1) Å, c = 12.534(1) Å, α = 108.679(9)°, β = 111.992(9)°, γ = 95.426(10)°, and Z = 2; 7, orthorhombic Pbca, with a = 14.567(1) Å, b = 13.145(1) Å, c = 14.865(1) Å, and Z = 8; 10, monoclinic P21/c, with a = 12.749(1) Å, b = 13.302(1) Å, c = 9.011(1) Å, β = 107.195(2)°, and Z = 4

Comparative Studies of Substitution Reactions of Rhenium(I) Dicarbonyl−Nitrosyl and Tricarbonyl Complexes in Aqueous Media

The ligand substitution behavior of [ReBr3(CO)3](NEt4)2 (1) and [ReBr3(CO)2(NO)]NEt4 (2) in aqueous media was compared. Ligand exchange reactions were performed with multidentate chelating systems such as picolylaminediacetic acid (L1; N,N‘,O,O‘), nitrilotriacetic acid (L2; N,O,O‘,O‘ ‘), iminodiacetic acid (L3; N,O,O‘), and bis(2-pyridyl)methane (L4; N,N‘). The products of the substitution reactions were isolated and characterized by means of IR, NMR, MS, and X-ray structure analysis. NMR and crystallographic analyses confirmed the formation of single structural isomers in all cases with a ligand-to-metal ratio of 1:1. With ligands L1 and L2 and precursor 1 the tridentately coordinated complexes [Re(L1)(CO)3] (7) and [Re(L2)(CO)3]2- (8) were formed. With precursor 2 the same ligands unexpectedly coordinated tetradentately after displacing a CO ligand, yielding complexes [Re(L1)(CO)(NO)] (3) and [Re(L2)(CO)(NO)]- (4). In both complexes NO was found to be coordinated trans to the carboxylate group. Time-dependent IR spectra of the reaction of 2 with ligand L1 and L2 confirmed the loss of one CO during the reaction. The product of the reaction of 2 with L3 was identified as the neutral complex [Re(L3)(CO)2(NO)] (5), again, with the nitrosyl coordinated trans to the carboxylate. With 1, ligand L3 formed the anionic complex [Re(L3)(CO)3]- (9). Finally the reactions with L4 yielded the complexes [ReBr(L4)(CO)2(NO)]Br (6) and [ReBr(L4)(CO)3] (10), in which bromide was found to be coordinated trans to the NO and CO, respectively. The X-ray structures of 3, 5−7, and 10 are discussed:  3, monoclinic P21/n, with a = 14.607(1) Å, b = 8.057(1) Å, c = 24.721(1) Å, β = 107.117(5)°, and Z = 4; 5, triclinic P1̄, with a = 6.909(1) Å, b = 9.882(1) Å, c = 14.283(1) Å, α = 89.246(9)°, β = 89.420(9)°, γ = 86.196(9)°, and Z = 4; 6, triclinic P1̄, with a = 9.823(1) Å, b = 10.094(1) Å, c = 12.534(1) Å, α = 108.679(9)°, β = 111.992(9)°, γ = 95.426(10)°, and Z = 2; 7, orthorhombic Pbca, with a = 14.567(1) Å, b = 13.145(1) Å, c = 14.865(1) Å, and Z = 8; 10, monoclinic P21/c, with a = 12.749(1) Å, b = 13.302(1) Å, c = 9.011(1) Å, β = 107.195(2)°, and Z = 4

Synthesis and Properties of Boranocarbonate: A Convenient in Situ CO Source for the Aqueous Preparation of [^99mTc(OH₂)₃(CO)₃]⁺

Synthesis and Properties of Boranocarbonate:  A Convenient in Situ CO Source for the Aqueous Preparation of [99mTc(OH2)3(CO)3]+</sup

Synthesis and Properties of Boranocarbonate: A Convenient in Situ CO Source for the Aqueous Preparation of [^99mTc(OH₂)₃(CO)₃]⁺

Synthesis and Properties of Boranocarbonate:  A Convenient in Situ CO Source for the Aqueous Preparation of [99mTc(OH2)3(CO)3]+</sup

Functionalization of Glucose at Position C-3 for Transition Metal Coordination: Organo-Rhenium Complexes with Carbohydrate Skeletons

Novel 3-O-[1,2;5,6-di-O-isopropylidene-α-d-glucofuranose] and 3-O-[d-glucose] derivatives with an iminodiacetate (N,O,O), a histidinate, and an N-(acetetyl)picolylamine (N,N,O) chelating system for tridentate coordination of the organometallic M(CO)3-fragment (M = Tc, Re) have been prepared. The chelates were introduced and assembled through reductive amination starting from 3-O-[1,2;5,6-di-O-isopropylidene-α-d-glucofuranose]-acetaldehyde. After deprotection, the pyranose derivatives were reacted with the precursor [NEt4]2[ReBr3(CO)3] to afford the corresponding organometallic complexes in yields between 54% and 94%. The NMR, MS, and IR analyses corroborated the tridentate coordination of the organometallic metal center exclusively via the synthetic chelates. In the case of the N-(acetyl)picolylamine derivative, the coordinative properties were further confirmed by X-ray structure analysis of the first Re(CO)3-d-glucofuranose complex. All glucose complexes unveiled good stability and solubility in organic and aqueous media