Iron(III) Metallacryptand and Metallacryptate Assemblies Derived from Aroylbis(<i>N</i>,<i>N</i>‑diethylthioureas)

The reaction of isophthaloylbis­(<i>N</i>,<i>N</i>-diethyl­thiourea), H₂L¹, with FeCl₃·6H₂O gives the dinuclear tris-complex [Fe₂(L¹)₃] (<b>5</b>), possessing a cryptand-like structure. A similar reaction with the ligand 2,6-dipicolinoylbis­(<i>N</i>,<i>N</i>-diethylthiourea), H₂L², however, results in the formation of the anionic, mononuclear Fe­(III) complex [Fe­(L²)₂]⁻ (<b>6</b>), which could be isolated as its “Tl⁺ salt” by the subsequent addition of Tl­(NO₃). A tighter view to the solid state structure of the obtained product, however, characterizes compound <b>6</b> as a one-dimensional coordination polymer, in which four-coordinate Tl⁺ ions connect the {[Fe­(L²)₂]⁻} units to infinite chains. When Fe³⁺ ions and Tl⁺ ions are added to H₂L² simultaneously in a one-pot reaction, a different product is obtained: a cationic trinuclear complex of the composition {M⊂[Fe₂(L²)₃]}⁺. It has been isolated as a PF₆^– salt and represents a {2}-metallacryptate with a nine-coordinate Tl⁺ ion in the central void. Structurally related products of the compositions {M⊂[Fe₂(L²)₃]}­(PF₆) (M = Na⁺, K⁺, Rb⁺) (<b>8</b>(PF₆)) could be isolated from analogous reactions with alkaline salts instead of Tl­(NO₃). {2}-Metallacryptates with larger central voids were synthesized with the ether-spaced aroylbis­(<i>N</i>,<i>N</i>-diethylthiourea) H₂L³. The compounds {M⊂[Fe₂(L³)₃]}­(PF₆) (M = K⁺, Rb⁺, Tl⁺ or Cs⁺) (<b>9</b>(PF₆)) were prepared by a similar protocol like those with H₂L² with the simultaneous addition of the metal ions to a solution of H₂L³. Due to the larger spacer between the aroylthiourea units, the coordination number of the central M⁺ ions is 12 by six carbonyl and six ether oxygen atoms. All products were characterized by elemental analysis, IR spectroscopy, and X-ray structure analysis. Cyclic voltammetric studies were carried out with the three representative complexes [Fe₂(L¹)₃], {K⊂[Fe₂(L²)₃]}­(PF₆), and {K⊂[Fe₂(L³)₃]}­(PF₆). The obtained voltammograms indicate the dependence of the redox properties of the oligonuclear systems on the conjugation in the organic backbones of the ligands

Aryl and NHC Compounds of Technetium and Rhenium

Air- and water-stable phenyl complexes with nitridotechnetium­(V) cores can be prepared by straightforward procedures. [TcNPh₂(PPh₃)₂] is formed by the reaction of [TcNCl₂(PPh₃)₂] with PhLi. The analogous N-heterocyclic carbene (NHC) compound [TcNPh₂(HL^Ph)₂], where HL^Ph is 1,3,4-triphenyl-1,2,4-triazol-5-ylidene, is available from (NBu₄)­[TcNCl₄] 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

Aryl and NHC Compounds of Technetium and Rhenium

Air- and water-stable phenyl complexes with nitridotechnetium­(V) cores can be prepared by straightforward procedures. [TcNPh₂(PPh₃)₂] is formed by the reaction of [TcNCl₂(PPh₃)₂] with PhLi. The analogous N-heterocyclic carbene (NHC) compound [TcNPh₂(HL^Ph)₂], where HL^Ph is 1,3,4-triphenyl-1,2,4-triazol-5-ylidene, is available from (NBu₄)­[TcNCl₄] 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

Synthesis, Characterization, and in Vitro Studies of Bis[1,3-diethyl-4,5-diarylimidazol-2-ylidene]gold(I/III) Complexes

Cationic bis­[1,3-diethyl-4,5-diarylimidazol-2-ylidene]­gold­(I) complexes with 4-OCH₃ or 4-F substituents in the aromatic rings and Br^– (<b>3a</b>,<b>b</b>) or BF₄^– (<b>7a</b>,<b>b</b>) counterions were synthesized, characterized, and investigated for tumor growth inhibitory properties in vitro. Analogous to auranofin, the N-heterocyclic carbenes (NHCs) were also combined with a phosphine ligand (triphenylphosphine, <b>4a</b>,<b>b</b>) and 2′,3′,4′,6′-tetra-<i>O</i>-acetyl-β-d-glucopyranosyl-1-thiolate (<b>5a</b>,<b>b</b>). The growth inhibitory effect against MCF-7, MDA-MB 231, and HT-29 cells, which is more than 10-fold higher than that of cisplatin or 5-FU, was independent of the oxidation state (Au­(III), <b>6a</b>,<b>b</b>) and the anionic counterion. Bis­[1,3-diethyl-4,5-bis­(4-fluorophenyl)­imidazol-2-ylidene]­gold­(I) bromide <b>3b</b> as the most cytotoxic compound reduced the growth of MCF-7 cells with IC₅₀ = 0.10 μM (cisplatin, 1.6 μM; 5-FU, 4.7 μM). The thioredoxin reductase (TrxR), the estrogen receptor (ER), and the cyclooxygenase (COX) enzymes, which have to be considered as possible targets based on the drug design, can be excluded from being involved in the mode of action

Fluoridonitrosyl Complexes of Technetium(I) and Technetium(II). Synthesis, Characterization, Reactions, and DFT Calculations

A mixture of [Tc­(NO)­F₅]^2– and [Tc­(NO)­(NH₃)₄F]⁺ is formed during the reaction of pertechnetate with acetohydroxamic acid (Haha) in aqueous HF. The blue pentafluoridonitrosyltechnetate­(II) has been isolated in crystalline form as potassium and rubidium salts, while the orange-red ammine complex crystallizes as bifluoride or PF₆^– salts. Reactions of [Tc­(NO)­F₅]^2– salts with HCl give the corresponding [Tc­(NO)­Cl_4/5]^−/2– complexes, while reflux in neat pyridine (py) results in the formation of the technetium­(I) cation [Tc­(NO)­(py)₄F]⁺, which can be crystallized as hexafluoridophosphate. The same compound can be synthesized directly from pertechnetate, Haha, HF, and py or by a ligand-exchange procedure starting from [Tc­(NO)­(NH₃)₄F]­(HF₂). The technetium­(I) cation [Tc­(NO)­(NH₃)₄F]⁺ can be oxidized electrochemically or by the reaction with Ce­(SO₄)₂ to give the corresponding Tc­(II) compound [Tc­(NO)­(NH₃)₄F]²⁺. The fluorido ligand in [Tc­(NO)­(NH₃)₄F]⁺ can be replaced by CF₃COO^–, leaving the “[Tc­(NO)­(NH₃)₄]²⁺ core” untouched. The experimental results are confirmed by density functional theory calculations on [Tc­(NO)­F₅]^2–, [Tc­(NO)­(py)₄F]⁺, [Tc­(NO)­(NH₃)₄F]⁺, and [Tc­(NO)­(NH₃)₄F]²⁺

Octafluorodirhenate(III) Revisited: Solid-State Preparation, Characterization, and Multiconfigurational Quantum Chemical Calculations

A simple method for the high-yield preparation of (NH₄)₂[Re₂F₈]·2H₂O has been developed that involves the reaction of (<i>n</i>-Bu₄N)₂[Re₂Cl₈] with molten ammonium bifluoride (NH₄HF₂). Using this method, the new salt [NH₄]₂[Re₂F₈]·2H₂O was prepared in ∼90% yield. The product was characterized in solution by ultraviolet–visible light (UV-vis) and ¹⁹F nuclear magnetic resonance (¹⁹F NMR) spectroscopies and in the solid-state by elemental analysis, powder X-ray diffraction (XRD), and infrared (IR) spectroscopy. Multiconfigurational CASSCF/CASPT2 quantum chemical calculations were performed to investigate the molecular and electronic structure, as well as the electronic absorption spectrum of the [Re₂F₈]^2– anion. The metal–metal bonding in the Re₂⁶⁺ unit was quantified in terms of effective bond order (EBO) and compared to that of its [Re₂Cl₈]^2– and [Re₂Br₈]^2– analogues

Neutral Gold Complexes with Tridentate <i>SNS</i> Thiosemicarbazide Ligands

Na­[AuCl₄]·2H₂O reacts with tridentate thiosemicarbazide ligands, H₂L1, derived from <i>N</i>-[<i>N</i>′,<i>N</i>′-dialkylamino­(thiocarbonyl)]­benzimidoyl chloride and thiosemicarbazides under formation of air-stable, green [AuCl­(L1)] complexes. The organic ligands coordinate in a planar <i>SNS</i> coordination mode. Small amounts of gold­(I) complexes of the composition [AuCl­(L3)] are formed as side-products, where L3 is an S-bonded 5-diethylamino-3-phenyl-1-thiocarbamoyl-1,2,4-triazole. The formation of the triazole L3 can be explained by the oxidation of H₂L1 to an intermediate thiatriazine L2 by Au³⁺, followed by a desulfurization reaction with ring contraction. The chloro ligands in the [AuCl­(L1)] complexes can readily be replaced by other monoanionic ligands such as SCN^– or CN^– giving [Au­(SCN)­(L1)] or [Au­(CN)­(L1)] complexes. The complexes described in this paper represent the first examples of fully characterized neutral Gold­(III) thiosemicarbazone complexes. All the [AuCl­(L1)] compounds present a remarkable cell growth inhibition against human MCF-7 breast cancer cells. However, systematic variation of the alkyl groups in the N(4)-position of the thiosemicarbazone building blocks as well as the replacement of the chloride by thiocyanate ligands do not considerably influence the biological activity. On the other hand, the reduction of Au^III to Au^I leads to a considerable decrease of the cytotoxicity

Synthesis and Biological Evaluation of Radio and Dye Labeled Amino Functionalized Dendritic Polyglycerol Sulfates as Multivalent Anti-Inflammatory Compounds

Herein we describe a platform technology for the synthesis and characterization of partially aminated, ³⁵S-labeled, dendritic polyglycerol sulfate (dPG³⁵S amine) and fluorescent dPGS indocarbocyanine (ICC) dye conjugates. These polymer conjugates, based on a biocompatible dendritic polyglycerol scaffold, exhibit a high affinity to inflamed tissue in vivo and represent promising candidates for therapeutic and diagnostic applications. By utilizing a one-step sequential copolymerization approach, dendritic polyglycerol (<i>M</i>_n ≈ 4.5 kDa) containing 9.4% <i>N</i>-phthalimide protected amine functionalities was prepared on a large scale. Sulfation and simultaneous radio labeling with ³⁵SO₃ pyridine complex, followed by cleavage of the N-phthalimide protecting groups, yielded dPG³⁵S amine as a beta emitting, inflammation specific probe with free amino functionalities for conjugation. Furthermore, efficient labeling procedures with ICC via iminothiolane modification and subsequent “Michael” addition of the maleimide functionalized ICC dye, as well as by amide formation via NHS derivatized ICC on a dPGS amine scaffold, are described. The dPGS-ICC conjugates were investigated with respect to their photophysical properties, and both the radiolabeled and fluorescent compounds were comparatively visualized in histological tissue sections (radio detection and fluorescence microscopy) of animals treated with dPGS. Furthermore, cellular uptake of dPGS-ICC was found in endothelial cord blood (HUVEC) and the epithelial lung cells (A549). The presented synthetic routes allow a reproducible, controlled synthesis of dPGS amine on kilogram scale applying a one-pot batch reaction process. dPGS amine can be used for analysis via radioactivity or fluorescence, thereby creating a new platform for inflammation specific, multimodal imaging purposes using other attachable probes or contrast agents