Iron complexes of bridging azo ligands in aqueous solution: changes in the thermal switching mechanism on coordination and oxidation state of metal centres.

Three azobenzenes CN(C6H4)-NN-(C5H4N) (py-iso), CN(C6H4)-NN-(C6H4)CN (cyano-iso) and CN(C6H4)-NN-(C6H4)NC (iso-iso) with good coordinating groups (pyridine, phenylcyano or phenylisocyano) at the ends of the diazenyl unit have been synthesized and fully characterised. These compounds have been used as ligands in the synthesis of water-soluble metallic species by coordination to {FeII(CN)53-} units, either in one or two of the anchoring groups of the derivatives. Both the azo derivatives and their complexes are photochemically active with respect to their trans-to-cis isomerisation process. Their cis-to-trans reverse thermal reaction has been thoroughly studied as a function of the donor groups, solvent, temperature and pressure, in order to gain insight into the rotation or inversion mechanisms involved in the process. A comparison of the isomerisation mechanism between the iron complexes and the corresponding free ligands revealed an interesting fine tuning of the process on coordination of the {FeII(CN)53-} moieties, which may even produce, in some cases, non-photoswitchable species containing typically photoactive units.

Amino acids with fluorescent tetrazine ethers as bioorthogonal handles for peptide modification.

A set of 3-bromo-1,2,4,5-tetrazines with three distinct substitutions have been used as reagents for late-stage functionalization of small molecules through nucleophilic aromatic substitution. Spectroscopic studies of the products obtained proved that tetrazine ethers are intrinsically fluorescent. This fluorescence is lost upon inverse Electron-Demand Diels-Alder (iEDDA) cycloaddition with strained alkenes. Tetrazine-phenol ethers are rather interesting because they can undergo rapid iEDDA reactions with a second order rate constant (k 2) compatible with bioorthogonal ligations. As a showcase, l-tyrosine was derivatized with 3-bromo-6-methyl-1,2,4,5-tetrazine and coupled to the peptide drug octreotide. This peptide was detected in cellular flow cytometry, and its fluorescence turned off through a bioorthogonal iEDDA cycloaddition with a strained alkene, showing for the first time the detection and reactivity of intrinsically fluorescent tetrazines in a biologically relevant context. The synthesis and characterization of fluorescent tetrazine ethers with bioorthogonal applicability pave the way for the generation of useful compounds for both detection and bioconjugation in vivo.

Homo- and heterometallic chiral dynamic architectures from allyl-palladium(II) building blocks.

New chiral tetranuclear square-like homo- and heterometallamacrocycles containing allyl-palladium and either {Pd(P-P)*} or {Pt(P-P)*} optically pure moieties (P-P* = (2S,3S)-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphanyl)butane ((S,S)-DIOP) and (2S,4S)-2,4-bis(diphenylphosphanyl)pentane ((S,S)-BDPP)) have been obtained by the self-assembly of [Pd(η3-2-Me-C3H4)(4-PPh2py)2]+ and [M(P-P)*(H2O)2]2+ building blocks in a 1 : 1 molar ratio. The supramolecular assemblies thus prepared [{Pd(η3-2-Me-C3H4)}2(4-PPh2py)4{M(P-P)*}2](CF3SO3)6 (M = Pd, Pt) have been fully characterised by multinuclear NMR spectroscopy and MS spectrometry. The structures display remarkable differences on their dynamic behaviour in solution that depend on the lability and thermodynamic strength of M-py bonds. The structural characteristics of the new metallamacrocyles obtained have also been unambiguously established by XRD analysis. The architectures have been assayed as catalytic precursors in the asymmetric allylic alkylation reaction.

Molecular Approach to Alkali-Metal Encapsulation by a Prussian Blue Analogue FeII/CoIII Cube in Aqueous Solution: A Kineticomechanistic Exchange Study.

The preparation of a series of alkali-metal inclusion complexes of the molecular cube [{CoIII(Me3-tacn)}4{FeII(CN)6}4]4- (Me3-tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane), a mixed-valent Prussian Blue analogue bearing bridging cyanido ligands, has been achieved by following a redox-triggered self-assembly process. The molecular cubes are extremely robust and soluble in aqueous media ranging from 5 M [H+] to 2 M [OH-]. All the complexes have been characterized by the standard mass spectometry, UV-vis, inductively coupled plasma, multinuclear NMR spectroscopy, and electrochemistry. Furthermore, X-ray diffraction analysis of the sodium and lithium salts has also been achieved, and the inclusion of moieties of the form {M-OH2}+ (M = Li, Na) is confirmed. These inclusion complexes in aqueous solution are rather inert to cation exchange and are characterized by a significant decrease in acidity of the confined water molecule due to hydrogen bonding inside the cubic cage. Exchange of the encapsulated cationic {M-OH2}+ or M+ units by other alkali metals has also been studied from a kineticomechanistic perspective at different concentrations, temperatures, ionic strengths, and pressures. In all cases, the thermal and pressure activation parameters obtained agree with a process that is dominated by differences in hydration of the cations entering and exiting the cage, although the size of the portal enabling the exchange also plays a determinant role, thus not allowing the large Cs+ cation to enter. All the exchange substitutions studied follow a thermodynamic sequence that relates with the size and polarizing capability of the different alkali cations; even so, the process can be reversed, allowing the entry of {Li-OH2}+ units upon adsorption of the cube on an anion exchange resin and subsequent washing with a Li+ solution.

Self-Assembled, Highly Positively Charged, Allyl-Pd Crowns: Cavity-Pocket-Driven Interactions of Fluoroanions.

A series of dodecanuclear highly positively charged homo- and heterometallamacrocycles [{Pd(η3 -2-Me-C3 H4 )}6 (4-PPh2 py)12 {M2 (tpbz)}3 ]18+ (M=Pd, Pt; tpbz=1,2,4,5-tetrakis(diphenylphosphanyl)benzene were synthesized by the quantitative self-assembly of {Pd(η3 -2-Me-C3 H4 )}+ , {M2 (tpbz)}4+ and 4-PPh2 py moieties in 2:1:4 molar ratio. The cationic assemblies were obtained as salts of different fluorinated anions with diverse sizes and electronic properties, namely BF4 - , PF6 - , SbF6 - and CF3 SO3 - . The new crown-like metallamacrocycles showed remarkable differences in their NMR spectra due to the presence of the different counteranions. On the basis of the observed variations, the metallacycles have been tested as catalytic precursors in allylic alkylation reactions. The anion-dependent activity and selectivity has been analysed and compared with that of the corresponding monometallic allylic corners [Pd(η3 -2-Me-C3 H4 )(4-PPh2 py)2 ]X (X=BF4 - , PF6 - , SbF6 - , CF3 SO3 - ). DFT calculations have been employed in order to help to the interpretation of the experimental data and to model the anion-crown interactions.

Self-Assembly and Properties of a Discrete Water-Soluble Prussian Blue Analogue FeII/CoIII Cube: Confinement of a Water Molecule in Aqueous Solution.

Novel types of water-soluble anionic cubic cages, K4[{CoIII(Me3-Tacn)}4{FeII(CN)6}4] and Na4[{CoIII(Me3-Tacn)}4{FeII(CN)6}4] (Me3-Tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane), were prepared by means of a mechanistically designed self-assembly process between [Co(Me3-Tacn)Cl3] and A4[FeII(CN)6] (M = Na or K), consisting of a rate-limiting outer-sphere redox step, followed by a fast substitution/inner-sphere redox reaction sequence. These compounds show remarkable stability in aqueous solution at different pH ranges, displaying neat protonation processes and reversible oxidation with peroxodisulfate to its neutral {FeIII4CoIII4} form. Furthermore, the cages behave as a robust and water-soluble molecular Prussian Blue analogue capable of encapsulating {Na-OH2}+ pairs and K+ cations in aqueous solution, with the cubic structure of the complex being preserved. Substitution of the {Na-OH2}+ pairs by K+ is easily accomplished, and the electrochemical properties of the sodium and potassium salts of the new cages have been found to be dramatically dependent on the encapsulated units.

Highly Cytotoxic Ruthenium(II)-Arene Complexes from Bulky 1-Pyrenylphosphane Ligands.

In the present study, the potential anti-neoplastic properties of a series of ruthenium half-sandwich complexes of formula [Ru(η6-arene)Cl2(PR1R2(1-pyrenyl))] (η6-arene = p-cymene and R1 = R2 = methyl for 1; η6-arene = methylbenzoate and R1 = R2 = methyl for 2; η6-arene = p-cymene and R1 = R2 = phenyl for 3; η6-arene = methylbenzoate and R1 = R2 = phenyl for 4; η6-arene = p-cymene, R1 = methyl and R2 = phenyl for 5; η6-arene = methylbenzoate, R1 = methyl and R2 = phenyl for 6) have been investigated. The six structurally related organoruthenium(II) compounds have been prepared in good yields and fully characterized; the X-ray structures of three of them, i.e., 1, 2, and 4, were determined. Although the piano-stool compounds contain a large polycyclic aromatic moiety, viz. a 1-pyrenyl group, they do not appear to interact with DNA. However, all the piano-stool complexes show significant cytotoxic properties against five human cell lines, namely, lung adenocarcinoma (A549), melanoma (A375), colorectal adenocarcinoma (SW620), breast adenocarcinoma (MCF7), and nontumorigenic epithelial breast (MCF10A), with IC50 values in the micromolar range for most of them. In addition, the most active compound, i.e., 2, induces a remarkable decrease of cell viability, that is in the nanomolar range, against two human neuroblastoma cell lines, namely, SK-N-BE(2) and CHLA-90. Complexes 1-6 are all capable of inducing apoptosis, but with various degrees of magnitude. Whereas 1, 3, 5, and 6 have no effect on the cell cycle of A375 cells, 2 and 4 can arrest it at the G2/M phase; furthermore, 2 (which is the most efficient compound of the series) also stops the cycle at the S phase, behaving as the well-known anticancer agent cisplatin. Finally, 2 is able to inhibit/reduce the cell migration of neuroblastoma SK-N-BE(2) cells.

Direct Asymmetric Hydrogenation of N-Methyl and N-Alkyl Imines with an Ir(III)H Catalyst.

A novel cationic [IrH(THF)(P,N)(imine)] [BArF] catalyst containing a P-stereogenic MaxPHOX ligand is described for the direct asymmetric hydrogenation of N-methyl and N-alkyl imines. This is the first catalytic system to attain high enantioselectivity (up to 94% ee) in this type of transformation. The labile tetrahydrofuran ligand allows for effective activation and reactivity, even at low temperatures. Density functional theory calculations allowed the rationalization of the stereochemical course of the reaction.

Kineticomechanistic Study of the Redox pH Cycling Processes Occurring on a Robust Water-Soluble Cyanido-Bridged Mixed-Valence {CoIII/FeII}2 Square.

A kineticomechanistic study of reversible electron-transfer processes undergone by the water-soluble, cyanido-bridged mixed-valence [{CoIII{(Me)2(µ-ET)cyclen}}2{(µ-NC)2FeII(CN)4}2]2- square has been carried out. The oxidation reaction consists of a two-step process with the participation of a solvent-assisted outer-sphere complex, as a result of the establishment of hydrogen bonds that involve the oxo groups of the oxidant (peroxodisulfate) and the terminal cyanido ligands of the tetrametallic square. The formally endergonic reduction reaction of the fully oxidized ([{CoIII{(Me)2(µ-ET)cyclen}}2{(µ-NC)2FeIII(CN)4}2]) core by water, producing hydrogen peroxide from water even at low pH values, is also a two-step process. Each one of these processes requires a set of two preequilibria involving the association of OH- and its subsequent deprotonation by a further OH- anion. The structure of the square compound in its fully protonated form has also been determined by X-ray diffraction and shows the existence of strong hydrogen-bonding interactions, in agreement with the rather high basicity of the terminal cyanido ligands. Likewise, density functional theory calculations on the tetrametallic complex showed zones with negative electrostatic potential around the FeII centers of the square that would account for the establishment of the hydrogen bonds found in the solid state. Spectroelectrochemistry experiments demonstrated the singular stability of the {CoIII/FeII}22- complex, as well as that of their partially, {Co2III/FeIIIFeII}-, and fully, {CoIII/FeIII}2, oxidized counterparts because no hysteresis was observed in these measurements.

Synthesis and coordination chemistry of enantiopure t-BuMeP(O)H.

Both enantiomers of the optically pure Secondary Phosphine Oxide (SPO) t-BuMeP(O)H (1) have been obtained by deboronation of phosphinous acid-borane t-BuMeP(O)H·BH3 (3) with HBF4 followed by hydrolysis of the intermediate adduct t-BuMeP(O)H·BF3 (1·BF3), which has been isolated and crystallographically characterised. Complexes [MCl(COD)(κP-(R)-1)] (M = Ir, Rh; 4 and 7 respectively) have been detected in solution but could not be isolated while trans-[RhCl(CO)(κP-(S)-1)2] (9) has been successfully obtained in good yield. Gold complex [AuCl(κP-(S)-1)] (10) has been prepared and its crystal structure shows the presence of aurophilic interactions. Three new ruthenium complexes ([RuCl2(η6-p-cymene)(κP-(R)-1)], 12), ([RuCl2(CO)3(κO-(S)-1)], 13) and trans-([RuCl2(CO)2(κP-(S)-1)2], 14) have been synthesised and fully characterised, including the crystal structure of 12. Four palladium coordination compounds have been prepared: trans-[PdCl2(κP-(S)-1)2] (trans-15), [Pd(µ-Cl)(κP-(S)-1)2]2 (16·OH and 16·BF2) and [Pd(µ-OAc)(κP-(S)-1)2] (17) and the crystal structure of complex 16·OH proves the pseudobidentate coordination of the two molecules of 1. Three organometallic allylpalladium complexes have been prepared namely [Pd(η3-Ph2C2H3)Cl(κP-(S)-1)] (18) and [Pd(η3-Ph2C2H3)(κP-(S)-1)2] (19·OH and 19·BF2). The crystal structure of 19·BF2 constitutes the first allylpalladium-SPO complex reported to date.

Half-sandwich complexes of Ir(iii), Rh(iii) and Ru(ii) with the MaxPhos ligand: metal centred chirality and cyclometallation.

The reaction of the acetylacetonates [(η5-C5Me5)M(acac)Cl] with (SP)-[HMaxPhos][BF4] afforded cationic complexes with the formula (SM,RP)-[(η5-C5Me5)MCl(MaxPhos)][BF4] (M = Rh (1), Ir (2)). The reaction of (SP)-MaxPhos with [RuCl(µ-Cl)(η6-p-MeC6H4iPr)]2 and NH4X afforded (SRu,RP)-[(η6-p-MeC6H4iPr)RuCl(MaxPhos)][X] (X = BF4 (3), PF6 (3')). The complexes have been completely characterized by analytical and spectroscopic means, including the determination of the crystal structures of 1, 2 and 3'. Treatment of the iridium complex 2 with AgBF4, at 253 K, resulted in the intramolecular cyclometallation of one of the tert-butyl substituents of the MaxPhos diphosphane ligand, affording a mixture of isomers of (SIr,RP1,SP2 and RIr,RP1,RP2)-[(η5-C5Me5)Ir(MaxPhos)][BF4] (4a and 4b). However, rhodium complex 1 and ruthenium complex 3 reacted with AgBF4 forming the expected unsaturated intermediates "(ηn-ring)M(MaxPhos)" which were trapped by MeCN, affording the cationic adducts (SM,RP)-[(ηn-ring)M(MaxPhos)(MeCN)][BF4]2 (M = Rh (5), Ru (6)). Only one epimer at the metal was isolated in high yield for the complexes 1, 2, 3, 3', 5 and 6 and the metallation of 2 to give 4 occurs with high diastereoselectivity.