Ruthenium Fragments Research Articles

Abstract A027: A photoactivatable microtubule-targeting rigidin prodrug

Abstract Analogues of marine alkaloid rigidins have been found to kill cancer cells at nanomolar concentrations by targeting the microtubule network. Here, a rigidin analogue containing a thioether group was “caged” by coordination of its thioether group to a photosensitive ruthenium polypyridyl complex. In the dark, the coordinated ruthenium fragment prevented the rigidin analogue from inhibiting tubulin polymerization and reduced its toxicity in 2D cancer cell lines monolayers, 3D lung cancer tumor spheroids (A549), and in a lung cancer tumor xenograft (A549) in nude mice. Photochemical activation of the prodrug upon green light irradiation led to the photosubstitution of the thioether ligand by water, thereby releasing the free rigidin analogue capable of inhibiting the polymerization of tubulin. In cancer cells, such photorelease was accompanied by a drastic reduction of cell growth, not only when the cells were grown in normoxia (21% O2) but also, remarkably, in hypoxic conditions (1% O2). In vivo, light activation of the compound in the tumor led to 30% tumor volume reduction, which represents the first demonstration of the efficacy of a ruthenium-based photocaged compounds in a tumor xenograft. In subsequent unpublished work, we fine-tuned the excited states in this complex by adding an amide functional group on the ruthenium cage. By doing so, a new caged complex was obtained that was activated by red light (instead of green light). We demonstrated the red light activation of this compound in solution and in vitro. This result demonstrates that functionalization of ruthenium cage with electron-withdrawing groups can radically enhance their photochemical properties, which is essential for this method development (red light penetrates better into tissues than green light). We will present our results of in vivo testing of this caged compound activated by tumor penetrable red light, where significant tumor reduction is seen in mice xenografted with subcutaneous human uveal melanoma liver metastatic cells. Citation Format: Alexander Kornienko, Sylvestre Bonnet. A photoactivatable microtubule-targeting rigidin prodrug [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A027.

A Novel Near-IR Absorbing Ruthenium(II) Complex as Photosensitizer for Photodynamic Therapy and its Cetuximab Bioconjugates.

A novel Ru(II) cyclometalated photosensitizer (PS), Ru-NH2 , for photodynamic therapy (PDT) of formula [Ru(appy)(bphen)2 ]PF6 (where appy=4-amino-2-phenylpyridine and bphen=bathophenanthroline) and its cetuximab (CTX) bioconjugates, Ru-Mal-CTX and Ru-BAA-CTX (where Mal=maleimide and BAA=benzoylacrylic acid) were synthesised and characterised. The photophysical properties of Ru-NH2 revealed absorption maxima around 580 nm with an absorption up to 725 nm. The generation of singlet oxygen (1 O2 ) upon light irradiation was confirmed with a 1 O2 quantum yield of 0.19 in acetonitrile. Preliminary in vitro experiments revealed the Ru-NH2 was nontoxic in the dark in CT-26 and SQ20B cell lines but showed outstanding phototoxicity when irradiated, reaching interesting phototoxicity indexes (PI) >370 at 670 nm, and >150 at 740 nm for CT-26 cells and >50 with NIR light in SQ20B cells. The antibody CTX was successfully attached to the complexes in view of the selective delivery of the PS to cancer cells. Up to four ruthenium fragments were anchored to the antibody (Ab), as confirmed by MALDI-TOF mass spectrometry. Nonetheless, the bioconjugates were not as photoactive as the Ru-NH2 complex.

A Flexible Synthetic Strategy for the Preparation of Heteroleptic Metallacycles of Porphyrins.

We present a stepwise synthetic strategy for the preparation of the unprecedented heteroleptic 2+2 neutral metallacycle [{t,c,c-RuCl2(CO)2}2(4′cisDPyP)(3′cisDPyP)] (5), in which two different 5,10-meso-dipyridylporphyrins, 4′cisDPyP [i.e., 5,10-bis(4′-pyridyl)-15,20-diphenylporphyrin] and 3′cisDPyP [i.e., 5,10-bis(3′-pyridyl)-15,20-diphenylporphyrin], are joined through equal 90°-angular Ru(II) connectors. The synthesis of 5 was accomplished through the preparation of a reactive ditopic intermediate in which one of the two pyridylporphyrins is linked to two neutral ruthenium fragments, each having one residual readily available coordination site (a dmso-O). Thus, compound 5 was obtained under mild conditions through two complementary routes: either by treatment of [{t,c,c-RuCl2(CO)2(dmso-O)}2(4′cisDPyP)] (3) with 1 equiv of 3′cisDPyP or, alternatively, by treatment of [{t,c,c-RuCl2(CO)2(dmso-O)}2(3′cisDPyP)] (4) with 1 equiv of 4′cisDPyP. Heteroleptic metallacycle 5 was isolated in pure form in acceptable yield and fully characterized. Spectroscopic data and a molecular model show that 5 has an L-shaped geometry, with the two porphyrins almost orthogonal to one another. The modular approach that we established is highly flexible and opens the way to several possible exciting developments.

Allenylidene and diazoalkane complexes of a half-sandwich mixed phosphine – phosphinite ruthenium fragment

Half-sandwich mixed phosphine-phosphinite ruthenium complexes [RuCp’Cl(PPh3)L] [Cp’ = Cp (1), Cp* (2)], and [RuCp*ClL2] (3) were prepared by substitution of the triphenylphosphine by the phosphinite ligand PPh2OCH2Ph, L, on the parent complexes [RuCp’Cl(PPh3)2]. Allenylidene compounds [Ru(η5-C5H5){CC = CPh2}(PPh3)L][PF6] (4) and [Ru(η5-C5Me5){CC = CPhR}(L)(L’)][BPh4] [L’ = PPh3(5), L (6); R = Ph (a), R = Me (b)] were obtained by reaction of compounds 1–3 with the appropriate propargylic alcohols 1,1-diphenyl-2-propyn-1-ol, and 2-phenyl-3-butyn-2-ol. Diazoalkane complexes [RuCp(N2CAr1Ar2)(PPh3)L][PF6] [Ar1 = Ar2 = Ph (7a), Ar1Ar2 = C12H8 (7b)] and [RuCp*{N2C(C12H8)}L2][PF6] (8) were obtained by reaction of 1 or 3 with the corresponding diazoalkanes in the presence of NaPF6. Complexes were characterized by IR and NMR spectroscopy and, in the case of compounds 1 and 7a, by X-ray diffraction analysis.

Photo-Uncaging of a Microtubule-Targeted Rigidin Analogue in Hypoxic Cancer Cells and in a Xenograft Mouse Model.

Marine alkaloid rigidins are cytotoxic compounds known to kill cancer cells at nanomolar concentrations by targeting the microtubule network. Here, a rigidin analogue containing a thioether group was "caged" by coordination of its thioether group to a photosensitive ruthenium complex. In the dark, the coordinated ruthenium fragment prevented the rigidin analogue from inhibiting tubulin polymerization and reduced its toxicity in 2D cancer cell line monolayers, 3D lung cancer tumor spheroids (A549), and a lung cancer tumor xenograft (A549) in nude mice. Photochemical activation of the prodrug upon green light irradiation led to the photosubstitution of the thioether ligand by water, thereby releasing the free rigidin analogue capable of inhibiting the polymerization of tubulin. In cancer cells, such photorelease was accompanied by a drastic reduction of cell growth, not only when the cells were grown in normoxia (21% O2) but also remarkably in hypoxic conditions (1% O2). In vivo, low toxicity was observed at a dose of 1 mg·kg-1 when the compound was injected intraperitoneally, and light activation of the compound in the tumor led to 30% tumor volume reduction, which represents the first demonstration of the safety and efficacy of ruthenium-based photoactivated chemotherapy compounds in a tumor xenograft.

Light-activated ruthenium (II)-bicalutamide prodrugs for prostate cancer

Targeted delivery of clinically approved anticancer drug to tumor sites is an effective way to achieve enhanced drug efficacy as well as reduced side effects and toxicity. Here bicalutamide is caged by the Ru(II) center through the nitrile group, and three photoactive Ru(II) complexes were designed and synthesized. Docking study showed that the ruthenium(II) fragments can effectively block the binding of complexes 1–3 with AR (androgen receptor) owing to the large steric structures, thus bicalutamide in complexes 1–3 could not interact with AR-LBD (ligand binding domain). Once irradiation with blue light (465nm), complexes 1–3 can release bicalutamide and anticancer Ru(II) fragments, which possesses dual-action of AR binding and DNA interaction simultaneously. In vitro cytotoxicity study on these complexes further confirmed that complexes 1–3 exhibited considerable cytotoxicity upon irradiation with blue light. Significantly, complex 3 could be activated at 660nm, which greatly increases the scope of complex 3 to treat deeper within tissue. Theoretical calculations showed that the lowest singlet excitation energy of complex 3 is lower than those of complexes 1–2, which explains the experimental results well. Moreover, the 3MC (metal centered) states of these complexes are more stable than their 3MLCT (metal to ligand charge transfer) states, indicating that the photoactive processes of these complexes are likely to result in ligand dissociation.

Xiaodong Chen

Angewandte Chemie International EditionVolume 58, Issue 12 p. 3686-3686 Author ProfileFree Access Xiaodong Chen First published: 19 October 2018 https://doi.org/10.1002/anie.201811655Citations: 2AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract “The greatest scientific advance of the last decade was genome editing. If I could be a piece of lab equipment, I would be a centrifuge …” Find out more about Xiaodong Chen in his Author Profile. Xiaodong Chen The author presented on this page has recently published his 10th article in Angewandte Chemie in the last 10 years: “Correlating the Surface Basicity of Metal Oxides with Photocatalytic Hydroxylation of Boronic Acids to Alcohols”: W. R. Leow, J. Yu, B. Li, B. Hu, W. Li, X. Chen, Angew. Chem. Int. Ed. 2018, 57, 9780; Angew. Chem. 2018, 130, 9928. The work of X. Chen has been featured on the back cover of Angewandte Chemie: “Unravelling the Correlation between the Aspect Ratio of Nanotubular Structures and Their Electrochemical Performance To Achieve High-Rate and Long-Life Lithium-Ion Batteries”: Y. Tang et al., Angew. Chem. Int. Ed. 2014, 53, 13488; Angew. Chem. 2014, 126, 13706. Date of birth: December 13, 1975 Position: Professor of Materials Science and Engineering, Nanyang Technological University, Singapore E-mail: chenxd@ntu.edu.sg Homepage: http://www.ntu.edu.sg/home/chenxd/index.html ORCID: 0000-0002-3312-1664 Education: 1999 BS, Fuzhou University 2002 MS with Minghua Liu, Chinese Academy of Sciences 2006 PhD in biochemistry with Harald Fuchs, Lifeng Chi, and Hans-Joachim Galla, University of Münster 2006–2008 Postdoctoral fellow with Chad A. Mirkin, Northwestern University Awards: 2009 Singapore NRF Fellowship; 2015 Small Young Innovator Award; 2016 Singapore NRF Investigatorship; 2017 Nanyang Research Award Current research interests: Conformal materials and devices; integrated nano–bio interfaces; dynamic processes of electrochemistry at interfaces Hobbies: Sipping fine tea, reading, badminton, and basketball The greatest scientific advance of the last decade was genome editing. If I could be a piece of lab equipment, I would be a centrifuge. The natural talent I would like to be gifted with are oratory or artistic skills. The most important future applications of my research are cyber-human systems. If I were a car I would be BMW i8. In a spare hour, I like to go to an amusement park with my kids. My favorite saying is “instead of giving someone a fish, why not teach him how to fish”. I advise my students to be brave and dedicated. My science “heroes” are Isaac Newton, Te-Pang Hou, and Chad A. Mirkin. If I had one year of paid leave I would do an internship at Apple Inc. In the future I see myself as an educator. The principal aspect of my personality is the Doctrine of the Mean, one of the philosophical doctrines of Confucianism. My favorite painter is Leonardo da Vinci. My favorite book is The Innovator's DNA (Clayton M. Christensen). My 5 top papers: 1“An Artificial Sensory Neuron with Tactile Perceptual Learning”: C. Wan et al., Adv. Mater. 2018, 30, 1801291. (An artificial neuron that can integrate and differentiate the spatiotemporal features of touched patterns for recognition.) 2“Reducing the Charge Carrier Transport Barrier in Functionally Layer-Graded Electrodes”: Y. Zhang et al., Angew. Chem. Int. Ed. 2017, 56, 14847; Angew. Chem. 2017, 129, 15043. (A composition gradient electrode was designed and fabricated to improve the effective Li-ion diffusivity as well as electronic conductivity within the electrode.) 3“Al2O3 Surface Complexation for Photocatalytic Organic Transformations”: W. R. Leow et al., J. Am. Chem. Soc. 2017, 139, 269. (Aluminum oxide, although thought to be an insulator, could induce an immense increase in the selective photo-oxidation of different benzyl alcohols in the presence of a large variety of dyes and O2.) 4“Skin-inspired Haptic Memory Arrays with Electrically Reconfigurable Architecture”: B. Zhu et al., Adv. Mater. 2016, 28, 1559. (The nonvolatile nature of a haptic memory device means that information on external pressure is retained after its removal of external pressure.) 5“Orthogonally modulated molecular transport junctions for resettable electronic logic gates”: F. Meng, Y.-M. Hervault, Q. Shao, B. Hu, L. Norel, S. Rigaut, X. Chen, Nat. Commun. 2014, 5, 3023. (These junctions were produced from chemically fabricated nanogaps functionalized with dithienylethene units bearing organometallic ruthenium fragments.) Citing Literature Volume58, Issue12March 18, 2019Pages 3686-3686 ReferencesRelatedInformation

Polynuclear ruthenium organometallic complexes containing a 1,3,5-triazine ligand: synthesis, DNA interaction, and biological activity.

It is now well established that ruthenium complexes are attractive alternatives to platinum-based anticancer agents. Most of the ruthenium compounds currently under investigation contain a single metal center. The synthesis of multinuclear analogues may provide access to novel complexes with enhanced biological activity. In this work, we have synthesized a set of three trinuclear complexes containing organometallic ruthenium fragments-(arene)RuCl-coordinated to a 2,4,6-tris(di-2-pyridylamino)-1,3,5-triazine core [(Arene = benzene (2), p-cymene (1), or hexamethylbenzene (3)]. The interaction of the complexes with DNA was extensively studied using a variety of biophysical probes as well as by molecular docking. The complexes bind strongly to DNA with apparent binding constants ranging from 2.20 to 4.79 × 104M-1. The binding constants from electronic absorption titrations were an order of magnitude greater. The mode of binding to the nucleic acid was not definitively determined, but the evidence pointed to some kind of non-specific electrostatic interaction. None of the complexes displayed any significant antimicrobial activity against the organisms that were studied and exhibited anticancer activity only at high (> 100μM) concentration.

Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex.

The rational design of anti-cancer agents includes a new approach based on ruthenium complexes that can act as nitric oxide (NO) donor agents against specific cellular targets. One of the most studied classes of those compounds is based on bis(bipyridine) ruthenium fragment and its derivative species. In this work, we present the chemical and cytotoxicity properties against the liver hepatocellular carcinoma cell line HepG2 of cis-[RuII(NO+)Cl(dcbpy)2]2- conjugated to a polyclonal antibody IgG (anti-VDAC) recognizing a cell surface marker. UV-visible bands of the ruthenium complex were assigned with the aid of density functional theory, which also allowed estimation of the structures that explain the biological effects of the ruthenium complex-IgG conjugate. The interaction of cis-[RuII(NO+)Cl(dcbpy)2]3- with mitochondria was evaluated due to the potential of these organelles as anti-cancer targets, and considering they interact with the anti-VDAC antibody. The cytotoxicity of cis-[RuII(NO+)Cl(dcbpy)2]3--anti-VDAC antibody was up to 80% greater in comparison to the free cis-[RuII(NO+)Cl(dcbpy)2]3- complex. We suggest that this effect is due to site-specific interaction of the complex followed by NO release.

Influence of highly basic phosphine ligand on the reactivity and hydrolysis of P4 and P4S3 supported by ruthenium fragments

Substitution of PPh3 in [RuCp(PPh3)2Cl] with highly basic PMe3 gave a remarkable change in the reactivity towards P4 and unexpectedly only the bimetallic complex cation [{RuCp(PMe3)2}2(μ,η1:1-P4)]2+ (3) was formed which was characterized by NMR spectroscopy and single crystal X-ray diffraction analysis. The equimolar reaction between the synthon [RuCp(PMe3)2]+ and the mixed cage P4S3 is highly selective quantitatively yielding only the product with η1-Pbasal coordination to ruthenium. On the other hand, the related [RuCp(PPh3)2]+ cation gave a 2:1 mixture of mono-η1-Pbasal and bimetallic complex. The solid state structure of [RuCp(PMe3)2(η1-Pbasal-P4S3)]+ (4) was solved by X-ray diffraction and represents the first example of X-ray structure of intact P4S3 coordinated to a mononuclear ruthenium organometallic fragment. Hydrolysis of the P4 ligand in 3 resulted mainly in two products, i.e. free H3PO3 and the diphosphane complex cation [{RuCp(PMe3)2}2(μ,η1:1-P2H4)]2+ (9), while in the presence of methanol two mononuclear complexes [RuCp(PMe3)2{P(OH)3}]+ (8) and [RuCp(PMe3)2{P(OCH3)3}]+ (10) in (2:1) ratio were selectively formed.

Synthesis and charge delocalization property of multimetallic molecular wires with diethynylthiophene bridges

Here we report properties of thiophene-rich, acetylide-type mono-, di- and tri-nuclear ruthenium molecular wires 1–4, which are prepared by rationally designed coupling of vinylidene intermediates. Electrochemical analysis of 1–3 reveals fully reversible redox waves, the numbers of which are equal to those of the ruthenium fragments. Spectroelectrochemical analysis of 2 and 3 reveals the clear step-by-step oxidation processes. Analysis of NIR absorption bands reveals that the monocationic species 2+ and 3+ are highly charge-delocalized species, which are further supported by DFT and TD-DFT calculations of their model complexes.

Homobimetallic hydride and dihydrogen complexes of ruthenium bearing N-heterocyclic carbene ligands

A series of new homobimetallic hydride complexes of ruthenium bearing N-heterocyclic carbene ligand of the type [{RuHCl(IMes)(PPh3)(CO)}2(4,4’-bpy)] (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) (4,4’-bpy = 4,4’-bipyridine) (2), [{RuHCl(IMes)(PPh3)(CO)}2(4,4’-dpyen)] (4,4’-dpyen = 1,2-bis(4-pyridyl)ethylene) (4), and [{RuHCl(IMes)(PPh3)(CO)}2(4,4’-dpyan)] (4,4’-dpyan = 1,2-bis(4-pyridyl)ethane) (5) has been synthesized and characterized starting from [RuHCl(IMes)(PPh3)(CO)] (1). The pyridyl-based ligands, (4,4’-bpy), (4,4’-dpyen), and (4,4’-dpyan) in these complexes act as the bridging ligands between the two ruthenium fragments. The bridging ligand in these bimetallic complexes is very labile. Reaction of these complexes with PMe3 led to extensive substitution of not only the bridging ligand but also the PPh3 ligands. Reaction of complexes 2, 4, and 5 with HOTf at low temperatures result in the formation of the corresponding dihydrogen complexes, [{RuCl(η2-H2)(IMes)(PPh3)(CO)}2(4,4’-bpy)][OTf]2 (9), [{RuCl(η2-H2)(IMes)(PPh3)(CO)}2(4,4’-dpyen)][OTf]2 (10), and [{RuCl(η2-H2)(IMes)(PPh3)(CO)}2(4,4’-dpyan)][OTf]2 (11), respectively. These are the first examples of homobimetallic ruthenium dihydrogen complexes bearing NHC ligands. The intact nature of the H–H bond in these derivatives was established by variable temperature 1H (400 MHz) spin-lattice relaxation time (T1, ms) measurements and from the H, D coupling constants of the corresponding HD isotopomers. The H–H distances (dHH) in these complexes fall in the range 0.95–0.98 Å. Hydrogen evolution takes place upon warming the dihydrogen complexes generated at low temperatures, indicating the labile nature of the H2 ligand in these complexes. The X-ray crystal structure of [{RuHCl(IMes)(PPh3)(CO)}2(4,4’-bpy)] complex (2) has been determined.

Unexpected higher stabilisation of two classical antiaromatic frameworks with a ruthenium fragment compared to the osmium counterpart: origin probed by DFT calculations.

Density functional theory (DFT) calculations were carried out to investigate the stability and aromaticity of metallapentalocyclobutadienes. The results reveal unexpected higher stabilisation achieved with a 4d ruthenium fragment compared to the 5d [corrected] osmium counterpart. Moreover, direct 1-3 metal-carbon bonding in the metallabutadiene unit of these two complexes is negligible.

Photochemical CO2-reduction catalyzed by mono- and dinuclear phenanthroline-extended tetramesityl porphyrin complexes.

We here present a comprehensive study on the light-induced catalytic CO2 reduction employing a number of mono- and dinuclear complexes with a phenanthroline-extended tetramesityl porphyrin ligand (). A stepwise synthesis of heterodinuclear complexes is possible because the phenanthroline moiety of the ligand can selectively coordinate a second metal center, e.g. Ru(tbbpy)2(2+) fragment, while any other metal can reside in the porphyrin cavity. We expanded our former studies to cobalt and iron compounds and synthesized the complexes , and , . Thorough catalytic investigation on the light-driven CO2 reduction of all compounds (M = 2H, Cu, Pd, Co, FeCl) was performed in a DMF solution in the presence of triethylamine (TEA) as a sacrificial electron donor. A very surprising wavelength dependence of the catalytic performance was observed. Turnover numbers (TONs) of CO were quantified and showed that redox active metals (i.e.M = Co and FeCl) in the porphyrin cavity caused the highest catalytic activity. After 24 hours of illumination with light λ > 305 nm reached a TONCO of 11.4 with our experimental setup without showing much decomposition. This value is twice as high as the TONCO determined for CoTPP (5.8) under the same conditions, which represented the most active porphyrinic system so far for photocatalytic CO2 reduction.

Anticancer Ruthenium(η6-p-cymene) Complexes of Nonsteroidal Anti-inflammatory Drug Derivatives

Oxicams are a versatile family of heterocyclic compounds, and the two representatives meloxicam and piroxicam are widely used drugs for the treatment of a variety of inflammatory and rheumatic diseases in humans. As cancer-associated inflammation is known to occur in carcinogenesis, we aimed to combine compounds carrying bioactive oxicam moieties with ruthenium(arene) fragments, known for anticancer activity. RuII(arene) complexes with methyl ester derivatives of the oxicam scaffold were prepared and characterized by standard methods and crystallographically. The organoruthenium compounds formed from RuII(η6-p-cymene) chlorido moieties and oxicam-based ligands were subjected to bioanalytical investigations to establish their physicochemical properties with regard to stability in DMSO and water as well as reactivity toward the amino acids l-histidine (His), l-methionine (Met), and l-cysteine (Cys) and the DNA model compound guanosine 5′-monophosphate (5′-GMP). The compounds hydrolyzed rapidly in water to g...

Contrasting reactivity behaviour of the [RuHCl(CO)(PNP)] complex with electrophilic reagents XOTf (X = H, CH3, Me3Si).

A new ruthenium pincer complex [RuHCl(CO)(PNP)] (PNP = PhCH2N(CH2CH2PPh2)2) () was synthesized and characterized. The reactivity of complex with electrophilic reagents XOTf (X = H, CH3, and Me3Si; OTf = CF3SO3) was studied by variable temperature NMR spectroscopy with an aim to observe and characterize sigma complexes of type [Ru(η(2)-HX)Cl(CO)(PNP)][OTf] (X = H (), CH3 (), Me3Si ()). Reaction of complex with HOTf resulted in the formation of the dihydrogen complex, [Ru(η(2)-H2)Cl(CO)(PNP)[OTf] (). On the other hand, the reaction between complex and MeOTf and Me3SiOTf resulted in the direct elimination of MeCl and Me3SiCl via a SN2 type of reaction without the intermediacy of the respective sigma complexes and . This contrasting reactivity behaviour has been rationalized taking into consideration the approach of the relatively bulky electrophiles CH3(+) and Me3Si(+) onto the hydride moiety of the ruthenium fragment, which is sterically hindered.

Orthogonally modulated molecular transport junctions for resettable electronic logic gates.

Individual molecules have been demonstrated to exhibit promising applications as functional components in the fabrication of computing nanocircuits. Based on their advantage in chemical tailorability, many molecular devices with advanced electronic functions have been developed, which can be further modulated by the introduction of external stimuli. Here, orthogonally modulated molecular transport junctions are achieved via chemically fabricated nanogaps functionalized with dithienylethene units bearing organometallic ruthenium fragments. The addressable and stepwise control of molecular isomerization can be repeatedly and reversibly completed with a judicious use of the orthogonal optical and electrochemical stimuli to reach the controllable switching of conductivity between two distinct states. These photo-/electro-cooperative nanodevices can be applied as resettable electronic logic gates for Boolean computing, such as a two-input OR and a three-input AND-OR. The proof-of-concept of such logic gates demonstrates the possibility to develop multifunctional molecular devices by rational chemical design.

The nature of the M–NO bond in [M(Imidazole)(PPIX)(L)]q complexes (M = Fe2+, Ru2+; L = NO+, NO[rad] and NO−; PPIX = Protoporphyrin IX)

Aiming at understanding the effect of the replacement of iron by ruthenium in the Protoporphyrin IX (PPIX) system of the heme group, in this work density functional theory calculations were performed to investigate the structures, nature of the M–NO bond and electronic spectra of the complexes [M(Im)(PPIX)(L)]q, where M=Fe2+ and Ru2+, Im=Imidazole ring, PPIX=Protoporphyrin IX of the heme group and L=NO+, NO and NO−. Energetic and structural results obtained at the B3LYP/SBKJC/6-31G(d) level of theory indicates that the NO coordinates preferentially through the nitrogen atom and its oxidized form NO+ produces more stable complexes. Charge and energy decomposition analysis revealed that, independent of the coordination mode, the interaction of NO species with the ruthenium fragment is stronger than with iron. TD-DFT calculations predict that the transition that can lead to photodissociation of the Ru–NO bond occurs at 419nm and if the NO coordinates to ruthenium in its oxidized form this transition is blue-shifted to 384nm. The results obtained in this work also gives support to conclude that ruthenium complexes with the protoporphyrin IX (PPIX) system can strongly bind NO, which can be used to capture NO species, and releasing it upon irradiation with visible light.

Synthesis and characterization of mono- and dinuclear phenanthroline-extended tetramesitylporphyrin complexes as well as UV-Vis and EPR studies on their one-electron reduced species

The syntheses of mononuclear compounds based on the fused porphyrin phenanthroline ligand (H(2)-1) and their corresponding dinuclear porphyrin bis-bipyridine ruthenium complexes are reported. The extended π-system of the ligand is able to store electron equivalents as could be proven by the single electron reduction with KC(8) (and/or Na(Hg)) followed by subsequent UV-Vis and EPR analysis. Electron reduction could also be achieved under light illumination in a dichloromethane-triethylamine mixture. The two coordination spheres of the ligand are different so that mononuclear or (hetero)dinuclear complexes can be isolated depending on the reaction conditions. We could successfully introduce Zn, Cu and Pd into the porphyrinic unit leading to a series of mononuclear (M-1) compounds. Further, we could attach the bis-(4,4'-di-tert-butyl-2,2'-bipyridine) ruthenium fragment (Ru(tbbpy)(2)(2+)) to obtain dinuclear (M-1-Ru) metal complexes. In the case of Zn-1 an X-ray crystal structure could be obtained confirming the selective metallation in the porphyrinic unit. All metal complexes were isolated and characterized with standard analytical tools (elemental analysis, mass spectrometry and NMR (or EPR) spectroscopy).

Thiazolyl-phosphine hydrochloride salts: effective auxiliary ligands for ruthenium-catalyzed nitrile hydration reactions and related amide bond forming processes in water

A series of water-soluble N-protonated thiazolyl-phosphine hydrochloride salts have been synthesized and coordinated to the ruthenium(II) fragment [RuCl2(η6-p-cymene)]. The resulting complexes were evaluated as potential catalysts for the selective hydration of nitriles to primary amides in environmentally friendly aqueous medium. The best results in terms of activity were achieved when tris(5-(2-aminothiazolyl))phosphine trihydrochloride was used as ligand. Using the Ru(II) complex 9 derived from this salt (3 mol%), the catalytic reactions proceeded cleanly in pure water at 100 °C without the assistance of any additive, affording the desired amides in high yields (>78%) after short reaction periods (0.5–7 h). The process was operative with both aromatic, heteroaromatic, α,β-unsaturated and aliphatic nitriles, and tolerated several functional groups. The utility of 9 in promoting the formation of primary amides in water by catalytic rearrangement of aldoximes and direct coupling of aldehydes with NH2OH·HCl has also been demonstrated.