Metal Complex Mediated Conjugation of Peptides to Nucleus Targeting Acridine Orange: A Modular Concept for Dual-Modality Imaging Agents

To target the nucleus of specific cells, trifunctional radiopharmaceuticals are required. We have synthesized acridine orange derivatives which comprise an imidazole-2-carbaldehyde function for coordination to the [Re(CO)3]+ or [99mTc(CO)3]+ core. Upon coordination, this aldehyde is activated and rapidly forms imines with amines from biological molecules. This metal-mediated imine formation allows for the conjugation of a nuclear targeting portion with a specific cell receptor binding function directly on the metal. With this concept, we have conjugated the acridine orange part to a bombesin peptide directly on the 99mTc core and in one step. In addition, a linker containing an integrated disulfide has been coupled to bombesin. LC/MS study showed that the disulfide was reductively cleaved with a 60 min half-life time. This concept enables the combination of a nucleus targeting agent with a specific cell receptor molecule directly on the metal without the need of separate conjugation prior to labeling, thus, a modular approach. High uptake of the BBN conjugate into PC-3 cells was detected by fluorescence microscopy, whereas uptake into B16BL6 cells was negligible

Synthesis, Characterization, and Structures of R₃EOTcO₃ Complexes (E = C, Si, Ge, Sn, Pb) and Related Compounds

AgTcO4 reacts with R3ECl compounds (E = C, Si, Ge, Sn, Pb; R = Me, iPr, tBu, Ph), tBu2SnCl2, or PhMgCl under formation of novel trioxotechnetium(VII) derivatives. The carbon and silicon derivatives readily undergo decomposition, which was proven by 99Tc NMR spectroscopy and the isolation of decomposition products such as [TcOCl3(THF)(OH2)]. Compounds [Ph3GeOTcO3], [(THF)Ph3SnOTcO3], [(O3TcO)SntBu2(OH)]2, and [(THF)4Mg(OTcO3)2] are more stable and were isolated in crystalline form and characterized by X-ray diffraction

Thiourea Derivatives as Potent Inhibitors of Aluminum Corrosion: Atomic-Level Insight into Adsorption and Inhibition Mechanisms

Suitable corrosion inhibitors are of prime importance in order to prevent degradation of surfaces by oxidizing chemicals. In this work we studied ten symmetrical thiourea derivatives on aluminum and their efficacy in preventing oxidation by hydrochloric acid computationally and experimentally. We carried out DFT calculations of the inhibitors in both tautomer forms adsorbed on an aluminum-terminated α-alumina surface, focusing on the structure and energetics of adsorption as well as electronic properties. Chemisorption is dominated by electron transfer from the inhibitor S atom toward the surface as well as into the first few layers of the solid. We find that the aggregated amount of transferred charge is an important parameter of the system that correlates with the inhibition efficiency as determined with potentiodynamic measurements. The measurements indicate that the thiourea derivatives are cathodic-type inhibitors, which hinder the reduction of protons and thus indirectly the surface oxidation. This is rationalized with the formation of a positively charged layer on the surface that may repel protons. Our results may serve to further improve corrosion inhibitors on this technologically important surface

Synthesis, Characterization, and Structures of R₃EOTcO₃ Complexes (E = C, Si, Ge, Sn, Pb) and Related Compounds

AgTcO4 reacts with R3ECl compounds (E = C, Si, Ge, Sn, Pb; R = Me, iPr, tBu, Ph), tBu2SnCl2, or PhMgCl under formation of novel trioxotechnetium(VII) derivatives. The carbon and silicon derivatives readily undergo decomposition, which was proven by 99Tc NMR spectroscopy and the isolation of decomposition products such as [TcOCl3(THF)(OH2)]. Compounds [Ph3GeOTcO3], [(THF)Ph3SnOTcO3], [(O3TcO)SntBu2(OH)]2, and [(THF)4Mg(OTcO3)2] are more stable and were isolated in crystalline form and characterized by X-ray diffraction

[Tc^I(CN)₃(CO)₃]^2- and [Re^I(CN)₃(CO)₃]^2-: Case Studies for the Binding Properties of CN^- and CO

The cyano carbonyl complexes [99Tc(CN)3(CO)3]2- and [Re(CN)3(CO)3]2- were synthesized and fully characterized. These complexes are additional members of the well-known d6 transition metal complex series [M(CN)3(CO)3]n-. The analytical data obtained in this study thus offer a unique opportunity to study similarities and differences of cyanide and carbonyl binding in transition metal complexes

[Tc^I(CN)₃(CO)₃]^2- and [Re^I(CN)₃(CO)₃]^2-: Case Studies for the Binding Properties of CN^- and CO

The cyano carbonyl complexes [99Tc(CN)3(CO)3]2- and [Re(CN)3(CO)3]2- were synthesized and fully characterized. These complexes are additional members of the well-known d6 transition metal complex series [M(CN)3(CO)3]n-. The analytical data obtained in this study thus offer a unique opportunity to study similarities and differences of cyanide and carbonyl binding in transition metal complexes

Toward Organometallic ^99mTc Imaging Agents: Synthesis of Water-Stable ⁹⁹Tc–NHC Complexes

99TcVO2–NHC complexes containing monodentate and bidentate N-heterocyclic carbenes (NHCs) have been prepared by the reactions of [TcO­(glyc)2]− (glyc = ethyleneglycolato) with 1,3-dimethylimidazoline-2-ylidene (L1), 1,1′-methylene-3,3′-dimethyl-4,4′-diimidazoline-2,2′-diylidene (L2), and 1,1′-methylene-3,3′-diethyl-4,4′-diimidazoline-2,2′-diylidene (L3) in THF. The resulting complexes were fully characterized and their stabilities investigated. While complexes with monodentate NHCs only are hydrolytically unstable, complexes containing bidentate NHCs are water-stable over a broad pH range. The high water stability allows interconversion of the {99TcVO2}+ core into {99TcVOCl}2+ with HCl as the H+ and Cl– source. An alternative procedure to obtain 99TcVO2–NHC complexes is the in situ deprotonation of imidazolium salts, enabling the preparation of 99TcVO2–NHC compounds without free NHCs, thus increasing the scope of NHC ligands drastically. The remarkable stability and pH-controllable reactivity of the new complexes underlines the potential of NHCs as stabilizing ligands for 99Tc complexes and paves the way for the first 99mTc–NHC complexes in the future

Synthesis and Reactivity of the 17 e⁻ Complex [Re^IIBr₄(CO)₂]²⁻: A Convenient Entry into Rhenium(II) Chemistry

The reduction of (Et4N)[ReIIIBr4(CO)2] (1) by 0.5 equiv of tetrakis-dimethylaminoethylene in acetonitrile yields directly the air-stable, 17-electron ReII synthon (Et4N)2[ReIIBr4(CO)2] (2) in nearly quantitative yield. The versatility of 2 as a synthon for ReII chemistry was demonstrated by substitution reactions of [ReIIBr4(CO)2]2− with different mono-, bi-, and tridentate ligands. The resulting ReII complexes form highly crystalline compounds, and the solid state structures of the neutral trans−cis-[ReIIBr2(CO)2(X)n] species (where X = imidazole, pyridine, or phenanthroline) could be determined. All complexes are stable under aerobic conditions, both as solids and in solution, and showed fully reversible one-electron ReII → ReI reductions between ca. −70 and −120 mV. Carbonyl stretching frequencies (νCO) of this new family of ReII complexes are observed in the 1990 cm−1 (A1) and 1830 (Eg) cm−1 regions. With complex 2, a wide variety of fundamental but so far unknown ReII complexes become accessible via facile substitution reactions

[Tc^I(CN)₃(CO)₃]^2- and [Re^I(CN)₃(CO)₃]^2-: Case Studies for the Binding Properties of CN^- and CO

The cyano carbonyl complexes [99Tc(CN)3(CO)3]2- and [Re(CN)3(CO)3]2- were synthesized and fully characterized. These complexes are additional members of the well-known d6 transition metal complex series [M(CN)3(CO)3]n-. The analytical data obtained in this study thus offer a unique opportunity to study similarities and differences of cyanide and carbonyl binding in transition metal complexes

Binding of 9-Methylguanine to [<i>cis</i>-Ru(2,2‘-bpy)₂]²⁺: First X-ray Structure of a <i>cis</i>-Bis Purine Complex of Ruthenium

Reaction of [cis-Ru(2,2‘-bpy)2(O3SCF3)2] (1) with 9-methylguanine (9-MeG) affords the cis-[Ru(2,2‘-bpy)2(9-MeG)2]2+ complex (2) in good yield. Two bases bind to the metal center via the N7 atoms. X-ray structure analysis of 2(SO3CF3)2 (monoclinic, P21/n, a = 12.5159(6) Å, b = 20.0904(13) Å, c = 17.1202(9) Å, β = 98.981(6)°, V = 4252.1(4) Å3, Z = 4) reveals that the two bases are in a head-to-tail (HT) orientation with base−base dihedral angle of 60.4°. NMR studies confirm that the complex is stable in water for hours, and no evidence for guanine substitution by solvent molecules was found