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We report the synthesis, characterization, and in vitro biological activities of [Re(η 6 -arene) 2 ] + -terpyridine conjugates and their Cu II complexes. The terpyridine (terpy) chelators were attached to the [Re(η 6 -arene) 2 ] + scaffold via secondary amine linkers allowing for heteroleptic mono- and homoleptic bis-terpyridine-substituted chelators. Complexation with CuCl 2 afforded the respective square pyramidal [Cu(terpy)Cl 2 ] complexes hosted on the [Re(η 6 -arene) 2 ] + scaffold. The chelator conjugates and their respective complexes were found to be remarkably cytotoxic against malignant HT29 and A549 human cancer cell lines in vitro with IC 50 values in the low micromolar range. Mitochondrial respiration disruption was identified as a possible mode of action of these novel drug candidates. Crucially, the [Re(η 6 -arene) 2 ] + hosts delivered water solubility of the otherwise insoluble [Cu(terpy)Cl 2 ] motif. Importantly, the homoleptic [ 99m Tc(η 6 -arene) 2 ] + -terpyridine conjugate is available in a single step, which enables the presented system to be used as a theranostic approach to modern medicinal inorganic chemistry.

The pursuit of molecular imaging for tumors has led to endeavors focused on targeting epidermal growth factor receptors (EGFR) through monoclonal antibodies or radionuclide-labelled EGF analogs with 99m Tc, 111 In, or 131 I. In this context, various 99m Tc-labeled EGFR inhibitors using quinazoline structures have been reported based on the so-called pendant approach and on two types of complexes and labelling strategies: "4 + 1" mixed ligand complexes and fac -tricarbonyl complexes. Apart from this approach, which alters lead structures by linking pharmacophores to chelator frameworks through different connectors, the integrated incorporation of topoisomerase and tyrosine kinase inhibitors into Re and 99m Tc complexes has not been explored. Here we present [M(η 6 -inhibitor) 2 ] + (M = Re, 99m Tc) and [Re(η 6 -bz)(η 6 -inhibitor)] + complexes, where the core structure of an EGFR tyrosine kinase inhibitor binds directly to the metal center. These complexes exhibit potential for tumor imaging: initial biological investigations highlight the influence of one versus two bound inhibitors on the metal center.

The search for new metal-based photosensitizers (PSs) for anticancer photodynamic therapy (PDT) is a fast-developing field of research. Knowing that polymetallic complexes bear a high potential as PDT PSs, in this study, we aimed at combining the known photophysical properties of a rhenium(I) tricarbonyl complex and a ruthenium(II) polypyridyl complex to prepare a ruthenium-rhenium binuclear complex that could act as a PS for anticancer PDT. Herein, we present the synthesis and characterization of such a system and discuss its stability in aqueous solution. In addition, one of our complexes prepared, which localized in mitochondria, was found to have some degree of selectivity towards two types of cancerous cells: human lung carcinoma A549 and human colon colorectal adenocarcinoma HT29, with interesting photo-index (PI) values of 135.1 and 256.4, respectively, compared to noncancerous retinal pigment epithelium RPE1 cells (22.4)., (© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Bis-arene sandwich complexes are generally prepared by the Fischer-Hafner reaction, which conditions are incompatible with most O- and N- functional groups. We report a new way for the synthesis of sandwich type complexes [Re(η 6 -arene) 2 ] + and [Re(η 6 -arene)(η 6 -benzene)] + from [Re(η 6 -napht) 2 ] + and [Re(η 6 -napht)(η 6 -benzene)] + , with functionalized arenes and pharmaceuticals. N-methylpyrrolidine (NMP) facilitates the substitution of naphthalene with the incoming arene. A series of fully characterized rhenium sandwich complexes with simple arenes, such as aniline, as well as with active compounds like lidocaine and melatonin are presented. With these rhenium compounds in hand, the radioactive sandwich complexes [ 99m Tc(η 6 -pharm) 2 ] + (pharm=pharmaceutical) can be unambiguously confirmed. The direct labelling of pharmaceuticals with 99m Tc through η 6 -coordination to phenyl rings and the confirmation of the structures with the rhenium homologues opens a path into molecular theranostics., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Mixed CO/NO-releasing molecules were prepared by conjugation of the 17-electron rhenium dicarbonyl cis-[Re(CO)2Br4](2-) complex to N-nitrosamine modified cyanocobalamin (B12) bio-vectors. The species were fully characterized by standard analytical techniques, including X-ray crystallography for cyanocobalamin-5'-O-pyrazine and () and its N-pyrazine nitrosylated derivative (). The N-nitrosamine B12 derivatives are able to liberate low NO doses in buffer solutions and appear to be "activated" towards NO release if in contact with cultured cells. Coordination of the cis-[Re(CO)2Br4](2-) complex on the axial cyanide of B12 allows for the combined loss of CO and NO from the conjugates. The mixed CO/NO-releasing molecules show cytoprotection in an ischemia-reperfusion model but no significant enhanced synergistic effects over the relative NORMs and CORMs building constituents.

Reaction of 1 with B(C6F5)3 under 1 bar of CO2 led to the instantaneous formation of the frustrated Lewis pair (FLP)-type species [ReHBr(NO)(PR3)2(η(2)-O═C═O-B(C6F5)3)] (2, R = iPr a, Cy b) possessing two cis-phosphines and O(CO2)-coordinated B(C6F5)3 groups as verified by NMR spectroscopy and supported by DFT calculations. The attachment of B(C6F5)3 in 2a,b establishes cooperative CO2 activation via the Re-H/B(C6F5)3 Lewis pair, with the Re-H bond playing the role of a Lewis base. The Re(I) η(1)-formato dimer [{Re(μ-Br)(NO)(η(1)-OCH═O-B(C6F5)3)(PiPr3)2}2] (3a) was generated from 2a and represents the first example of a stable rhenium complex bearing two cis-aligned, sterically bulky PiPr3 ligands. Reaction of 3a with H2 cleaved the μ-Br bridges, producing the stable and fully characterized formato dihydrogen complex [ReBrH2(NO)(η(1)-OCH═O-B(C6F5)3)(PiPr3)2] (4a) bearing trans-phosphines. Stoichiometric CO2 reduction of 4a with Et3SiH led to heterolytic splitting of H2 along with formation of bis(triethylsilyl)acetal ((Et3SiO)2CH2, 7). Catalytic reduction of CO2 with Et3SiH was also accomplished with the catalysts 1a,b/B(C6F5)3, 3a, and 4a, showing turnover frequencies (TOFs) between 4 and 9 h(-1). The stoichiometric reaction of 4a with the sterically hindered base 2,2,6,6-tetramethylpiperidine (TMP) furnished H2 ligand deprotonation. Hydrogenations of CO2 using 1a,b/B(C6F5)3, 3a, and 4a as catalysts gave in the presence of TMP TOFs of up to 7.5 h(-1), producing [TMPH][formate] (11). The influence of various bases (R2NH, R = iPr, Cy, SiMe3, 2,4,6-tri-tert-butylpyridine, NEt3, PtBu3) was studied in greater detail, pointing to two crucial factors of the CO2 hydrogenations: the steric bulk and the basicity of the base.

Diiodo Re(I) complexes [ReI2(NO)(PR3)2(L)] (3, L = H2O; 4 , L = H2; R = iPr a, Cy b) were prepared and found to exhibit in the presence of "hydrosilane/B(C6F5)3" co-catalytic systems excellent activities and longevities in the hydrogenation of terminal and internal alkenes. Comprehensive mechanistic studies showed an inverse kinetic isotope effect, fast H2/D2 scrambling and slow alkene isomerizations pointing to an Osborn type hydrogenation cycle with rate determining reductive elimination of the alkane. In the catalysts' activation stage phosphonium borates [R3PH][HB(C6F5)3] (6, R = iPr a, Cy b) are formed. VT (29)Si- and (15)N NMR experiments, and dispersion corrected DFT calculations verified the following facts: (1) Coordination of the silylium cation to the ONO atom facilitates nitrosyl bending; (2) The bent nitrosyl promotes the heterolytic cleavage of the H-H bond and protonation of a phosphine ligand; (3) H2 adds in a bifunctional manner across the Re-N bond. Nitrosyl bending and phosphine loss help to create two vacant sites, thus triggering the high hydrogenation activities of the formed "superelectrophilic" rhenium centers.

Cyanocobalamin (B(12)) offers a biocompatible scaffold for CO-releasing 17-electron dicarbonyl complexes based on the cis-trans-[Re(II)(CO)(2)Br(2)](0) core. A Co-C≡N-Re conjugate is produced in a short time and high yield from the reaction of [Et(4)N](2)[Re(II)Br(4)(CO)(2)] (ReCORM-1) with B(12). The B(12)-Re(II)(CO)(2) derivatives show a number of features which make them pharmaceutically acceptable CO-releasing molecules (CORMs). These cobalamin conjugates are characterized by an improved stability in aqueous aerobic media over the metal complex alone, and afford effective therapeutic protection against ischemia-reperfusion injury in cultured cardiomyocytes. The non-toxicity (at μM concentrations) of the resulting metal fragment after CO release is attributed to the oxidation of the metal and formation in solution of the ReO(4)(-) anion, which is among the least toxic of all of the rare inorganic compounds. Theoretical and experimental studies aimed at elucidating the aqueous chemistry of ReCORM-1 are also described.

Carbon monoxide releasing molecules (CO-RMs) are a newly emerging class of compounds of pharmacological interest. Among the transition metal-based CO-RMs, 17-electron complexes of general formula cis-trans-[Re(II)(CO)(2)Br(2)L(2)] are promising candidates but their poor hydrophilicity hampers future applications. In an effort to increase water solubility of d(5) dicarbonyl rhenium CO-RMs, the reaction of the cis-[Re(II)(CO)(2)Br(4)](2-) anion with bridging aromatic ligands of the pyridine and diazine type was investigated. Mononuclear and binuclear complexes are presented and it is shown that the nature of the bridging ligand critically dictates the formation of either species. Most complexes retained their fundamental CO-releasing properties. The synthesis of the molecules together with structural, spectroscopic and theoretical details are discussed.

Insights into the interaction of the [Re(H2O)3(CO)3]+ complex (1) with the DNA fragment d(CpGpG) have been obtained by one- (1D) and two-dimensional (2D) NMR spectroscopy. The H8 resonances of the single major [Re(H2O)d(CpGpG)(CO)3]- adduct (2) exhibit pH-independent chemical shift changes attributable to metal N7 binding. The structure of this adduct has been characterized by molecular modeling studies based on 1D and 2D NMR data. In solution, 2 shows the presence of two N7-coordinated guanine moieties in a head-to-head (HH) orientation as evidenced by G2H8/G3H8 cross-peaks in the 1H-1H NOESY NMR spectrum. The presence of the 5'-bridging phosphodiester appears to stabilize the HH1 L conformer, as was previously described for related Pt and Rh complexes.

We have prepared four complexes of the type [Re(guanine)(2)(X)(CO)(3)] (guanine = 9-methylguanine or 7-methylguanine, X = H(2)O or Br) in order to understand the factors determining the orientation of coordinated purine ligands around the [Re(CO)(3)](+) core. The 9-methylguanine ligand (9-MeG) was chosen as the simplest N(9) derivatized guanine, and 7-methylguanine (7-MeG) was chosen because metal binding to N(9) does not impose steric hindrance. Two types of structures have been elucidated by X-ray crystallography, an HH (head-to-head) and HT (head-to-tail) conformer for each of the guanines. All complexes crystallize in monoclinic space groups: [Re(9-MeG)(2)(H(2)O)(CO)(3)]ClO(4) (2) in P2(1)/n with a = 12.3307(10) A, b = 16.2620(14) A, c = 13.7171(11) A, and beta = 105.525(9) degrees, V = 2650.2(4) A(3), with the two bases in HT orientation and its conformer [Re(9-MeG)(2)(H(2)O)(CO)(3)]Br (3) in P2(1)/n with a = 15.626(13) A, b = 9.5269(5) A, c = 15.4078(13) A, and beta = 76.951(1) degrees, V = 2234.5(3) A(3), and the two bases in an HH orientation. Similarly, [Re(7-MeG)(2)(H(2)O)(CO)(3)]ClO(4) (4) crystallizes in P2(1)/c with a = 13.0708(9) A, b = 15.4082(7) A, c = 14.316(9) A, and beta = 117.236(7) degrees, V = 2563.5(3) A(3), and exhibits an HT orientation and [ReBr(7-MeG)(2)(CO)(3)] (5) in P2/c with a = 17.5117(9) A, b = 9.8842(7) A, c = 15.3539(1) A, and beta = 100.824(7) degrees, V = 2610.3(3) A(3), and shows an HH orientation. When crystals of any of these complex pairs are dissolved in D(2)O, the (1)H NMR spectrum shows a single peak for the H(8) resonance of the respective coordinated purine indicating a rapid equilibrium between HH and HT conformations in solution. DFT calculations simulating the rotation of one ligand around its Re-N bond showed energetic barriers of less than 8.7 kcal/mol. We find no hypochromic effect in the Raman spectrum of 3, which showed base stacking in the solid state. Neither steric interactions nor hydrogen bonding are important in determining the orientation of the ligands in the coordination sphere.

In this article, we present the serendipitous synthesis of the unknown Re(I) complex [(OPPh3)Re(NO)2Cl3] (3) that we obtained reacting the Re(V) complex trans-[(PPh3)2ReOCl3] (1) with NO gas in presence of CH3COOH. We found that 3 reacts with 1,3-bis (2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene (IMes) to yield a stable oximate—Re(III) complex [(OPPh3)Re(NO)(ON＝IMes)Cl3] (4). We speculate that the IMes reacts with a bent NO, because the DFT calculations excluded the formation of both dimeric and η2–NO complexes in solution. The reactivity of the NO toward the carbene is probably due to an internal fluxional process in which the NO passes from linear to bent, triggered by the π-electrons given by the three chlorides to the Re through the mesomeric effect. [ABSTRACT FROM AUTHOR]