PEGylated Molybdenum-Iodine Nanocluster as a Promising Radiodynamic Agent against Prostatic Adenocarcinoma.

The combination of photodynamic therapy and radiotherapy has given rise to a modality called radiodynamic therapy (RDT), based on reactive oxygen species-producing radiosensitizers. The production of singlet oxygen, O2(1Δg), by octahedral molybdenum (Mo6) clusters upon X-ray irradiation allows for simplification of the architecture of radiosensitizing systems. In this context, we prepared a radiosensitizing system using copper-free click chemistry between a Mo6 cluster bearing azido ligands and the homo-bifunctional linker bis-dPEG11-DBCO. The resulting compound formed nanoparticles, which featured production of O2(1Δg) and efficient cellular uptake, leading to remarkable photo- and radiotoxic effects against the prostatic adenocarcinoma TRAMP-C2 cell line. Spheroids of TRAMP-C2 cells were also used for evaluation of toxicity and phototoxicity. In vivo experiments on a mouse model demonstrated that subcutaneous injection of the nanoparticles is a safe administration mode at a dose of up to 0.08 g kg-1. The reported results confirm the relevancy of Mo6-based radiosensitizing nanosystems for RDT.

Stereochemical Behavior of Pairs of P-stereogenic Phosphanyl Groups at the Dimethylxanthene Backbone.

The P-stereogenic bis(phosphanes) 7 and 9, featuring pairs of P(Mes)-ethynyl or vinyl substituents at the dimethyl xanthene backbone show rather low barriers of stereochemical inversion at phosphorus. π-Conjugative effects are probably causing these low inversion barriers. Compound 7 reacted with B(C6 F5 )3 to form the nine-membered heterocyclic product 10, featuring a [P]-C≡C-B(C6 F5 )3 substituent. Compound 7 was converted to the bis[P(Mes)vinyl] xanthene derivative 9, which gave the zwitterionic P(H)(Mes)-CH=CH-B(C6 F5 )3 containing product 16 upon treatment with B(C6 F5 )3 . Thermally induced epimerization barriers at phosphorus of ca. 20 to 27 kcal mol-1 were calculated by DFT for the alkenyl- and alkynyl-P derived systems 6 to 9, 15 and 16 and experimentally determined for the examples 7 and 16.

"Activated Borane" - A Porous Borane Cluster Network as an Effective Adsorbent for Removing Organic Pollutants.

The unprecedented co-thermolysis of decaborane(14) (nido-B10 H14 ) and toluene results in a novel porous material (that we have named "activated borane") containing micropores between 1.0 and 1.5 nm in diameter and a specific surface area of 774 m2 g-1 (Ar, 87 K) that is thermally stable up to 1000 °C. Solid state 1 H, 11 B and 13 C MAS NMR, UV-vis and IR spectroscopies suggest an amorphous structure of borane clusters interconnected by toluene moieties in a ratio of about three toluene molecules for every borane cluster. In addition, the structure contains Lewis-acidic tri-coordinated boron sites giving it some unique properties. Activated borane displays high sorption capacity for pollutants such as sulfamethoxazole, tramadol, diclofenac and bisphenol A that exceed the capacity of commercially-available activated carbon. The consistency in properties for each batch made, and the ease of its synthesis, make activated borane a promising porous material worthy of broad attention.

Direct Phenylation of nido-B10H14.

As a preliminary step toward its condensation into the porous polymer Activated Borane, the thermolysis of nido-B10H14 (1) in benzene at 200 °C results in the generation of a number of phenylated borane molecular species. The principal product is the new monophenylated compound 5-Ph-nido-B10H13 (2), isolated in 48% yield (based on consumption of 1) and structurally characterized by single-crystal X-ray diffraction analysis, NMR, and mass spectrometry along with other minor products, such as 6-Ph-nido-B10H13 (3), for which we observe UV-light-driven conversion into 2 via a "vertex-flip" mechanism, and novel diphenylated 5,8-Ph2-nido-B10H12 (4). Together, the phenylated derivatives provide a valuable insight into the assembly of Activated Borane and ultimately inform on its structure. The new compounds also display strong blue fluorescence in both solid-state and in solution and are the first examples of the direct phenylation of nido-B10H14, thus opening the door to the straight-forward synthesis of highly luminescent organic-borane hybrid systems.

Frustrated Lewis-Pair Neighbors at the Xanthene Framework: Epimerization at Phosphorus and Cooperative Formation of Macrocyclic Adduct Structures.

Attachment of a pair of P-stereogenic mesityl(alkynyl)phosphanyl groups at the 4- and 5-positions of a 9,9-dimethylxanthene framework gave mixtures of the respective rac- and meso-bisphosphanyl diastereoisomers. They slowly epimerized in a thermally induced reaction with Gibbs activation barriers of about 25 kcal mol-1 at room temperature (measured and DFT calculated). The reaction of the meso-mesityl(tert-butylethynyl)phosphanyl derivative with two molar equivalents of Piers' borane [HB(C6 F5 )2 ] led to the formation of the alkylidene-bridged geminal bisphosphane/borane-frustrated Lewis pair system. The compound was obtained enriched (>85 %) in the rac diastereoisomer. With a variety of bifunctional donor substrates, the rac-bis-P/B FLP formed macrocyclic compounds. They were all formally derived from meso-configurated diastereoisomers of the bisphosphanylxanthene backbone.

Alkyne 1,1-Hydroboration to a Reactive Frustrated P/B-H Lewis Pair.

The Mes2 P-C≡C-SiMe3 alkyne reacts with the borane H2 B-Fmes by means of a rare 1,1-hydroboration reaction to give an unsaturated C2 -bridged frustrated P/B-H Lewis pair. Most of its reactions are determined by the presence of the B-H functionality at the FLP function and the activated connecting carbon-carbon double bond. It reduces carbon monoxide to the formyl stage. With nitriles it reacts in an extraordinary way: it undergoes a reaction sequence that eventually results in the formation of a P-substituted dihydro-1,2-azaborole derivative. Several similar examples were found. In one case a P-ylide was isolated that was related to an intermediate of the reaction sequence. It subsequently opened in an alternative way to give an alkenyl borane product.

Selective Gold-Catalysed Synthesis of Cyanamides and 1-Substituted 1H-Tetrazol-5-Amines from Isocyanides.

The newly discovered gold-catalysed reaction of isocyanides with hydrazoic acid generated in situ from trimethylsilyl azide and methanol (or, alternatively, from NaN3 /AcOH) produces either cyanamides or 1-substituted 1H-tetrazol-5-amines, depending on the amount of available HN3 . The reaction proceeds selectively and in generally high yields of either product, thus providing a particularly convenient access to a wide range of substituted 1H-tetrazol-5-amines that are rather difficult to access otherwise.

Synthesis and Catalytic Use of Gold(I) Complexes Containing a Hemilabile Phosphanylferrocene Nitrile Donor.

Removal of the chloride ligand from [AuCl(1-κP)] (2) containing a P-monodentate 1'-(diphenylphosphanyl)-1-cyanoferrocene ligand (1), by using silver(I) salts affords cationic complexes of the type [Au(1)]X, which exist either as cyclic dimers [Au(1)]2 X2 (3 a, X=SbF6 ; 3 c, X=NTf2 ) or linear coordination polymers [Au(1)]n Xn (3 a', X=SbF6 ; 3 b', X=ClO4 ), depending on anion X and the isolation procedure. As demonstrated for 3 a', the polymers can be readily cleaved by the addition of donors, such as Cl(-) , tetrahydrothiophene (tht) or 1, giving rise to the parent compound 2, [Au(tht)(1-κP)][SbF6 ] (5 a) or [Au(1-κP)2 ][SbF6 ] (4 a), respectively, of which the last two compounds can also be prepared by stepwise replacement of tht in [Au(1-κP)2 ][SbF6 ]. The particular combination of a firmly coordinated (phosphane) and a dissociable (nitrile) donor moieties renders complexes 3/3' attractive for catalysis because they can serve as shelf-stable precursors of coordinatively unsaturated Au(I) fragments, analogous to those that result from the widely used [Au(PR3 )(RCN)]X catalysts. The catalytic properties of the Au-1 complexes were evaluated in model annulation reactions, such as the synthesis of 2,3-dimethylfuran from (Z)-3-methylpent-2-en-4-yn-1-ol and oxidative cyclisation of alkynes with nitriles to produce 2,5-disubstituted 1,3-oxazoles. Of the compounds tested (2, 3 a', 3 b', 3 a, 4 a and 5 a), the best results were consistently achieved with dimer 3 c, which has good solubility in organic solvents and only one firmly bound donor at the gold atom. This compound was advantageously used in the key steps of annuloline and rosefuran syntheses.

1'-(Diphenylphosphino)-1-cyanoferrocene: a simple ligand with complicated coordination behavior toward copper(I).

1'-(Diphenylphosphino)-1-cyanoferrocene (3), a new donor-asymmetric ferrocene ligand obtained in two steps from 1'-(diphenylphosphino)ferrocene-1-carboxaldehyde, reacts with CuCl at a Cu/3 molar ratio of 1:1 to give the heterocubane complex [Cu(µ3-Cl)(3-κP)]4 (4). When the Cu/3 ratio is changed to 1:2 or 1:3, the reaction takes a different course, producing the P,N-bridged dimer [CuCl(3-κP)(µ(P,N)-3)]2 (5) after crystallization. Notably, CuBr and CuI behave differently, affording the corresponding 2D coordination polymers [CuX(µ(P,N)-3)]n [X = I (7), and Br (8)], regardless of the Cu/3 ratio. Reaction of 3 with sources of naked Cu(+), such as [Cu(MeCN)4](+) salts or their synthetic equivalents, provides the 1D coordination polymer [Cu(MeCN-κN)(µ(P,N)-3)][BF4] (9) or salts of a quadruply bridged dicopper(I) cation, [Cu2(µ(P,N)-3)4]X2 ([10]X2), depending on the Cu/3 molar ratio (1:1 vs 1:2 and 1:3). Except for 4, in which 3 binds as a simple P-monodentate ligand, the complexes reported here represent the first structurally characterized compounds in which a phosphinonitrile ligand coordinates through both of its soft donor moieties, thereby extending the coordination chemistry of these ligands.

Synthesis and catalytic properties of palladium(II) complexes with P,π-chelating ferrocene phosphinoallyl ligands and their non-tethered analogues.

Hybrid phosphines usually combine a phosphine moiety with another heteroatom secondary donor group in their structures while compounds equipped with hydrocarbyl π-donor moieties remain uncommon. This contribution reports the synthesis and structural characterization of the first P/π-allyl-chelating complexes that were obtained using the structurally flexible and redox-active ferrocene unit as the scaffold, viz. [PdCl(R2PfcCHCHCH2-η3:κP)] (1R; R = Ph and cyclohexyl (Cy); fc = ferrocene-1,1'-diyl). These compounds were synthesized from the respective phosphinoferrocene carboxaldehydes R2PfcCHO via reaction with vinylmagnesium bromide to generate 1-(phosphinoferrocenyl)allyl alcohols, which were subsequently acetylated. The resulting allyl acetates reacted smoothly with [Pd2(dba)3]/[Et3NH]Cl (dba = dibenzylideneacetone) to produce the target compounds. Complexes 1R and their nontethered analogues [PdCl(η3-C3H5)(FcPR2-κP)] (5R; Fc = ferrocenyl) were evaluated as pre-catalysts for the Pd-catalysed allylic amination of cinnamyl acetate with aliphatic amines and Suzuki-Miyaura-type cross-coupling of 4-tolylboronic acid with benzoyl chloride. In these reactions, better results were achieved with compounds 5R (particularly with 5Ph), presumably because they form more stable LPd(0)-type catalysts.

"Activated Borane": A Porous Borane Cluster Polymer as an Efficient Lewis Acid-Based Catalyst.

Borane cluster-based porous covalent networks, named activated borane (ActB), were prepared by cothermolysis of decaborane(14) (nido-B10H14) and selected hydrocarbons (toluene, ActB-Tol; cyclohexane, ActB-cyHx; and n-hexane, ActB-nHx) under anaerobic conditions. These amorphous solid powders exhibit different textural and Lewis acid (LA) properties that vary depending on the nature of the constituent organic linker. For ActB-Tol, its LA strength even approaches that of the commonly used molecular LA, B(C6F5)3. Most notably, ActBs can act as heterogeneous LA catalysts in hydrosilylation/deoxygenation reactions with various carbonyl substrates as well as in the gas-phase dehydration of ethanol. These studies reveal the potential of ActBs in catalytic applications, showing (a) the possibility for tuning catalytic reaction outcomes (selectivity) in hydrosilylation/deoxygenation reactions by changing the material's composition and (b) the very high activity toward ethanol dehydration that exceeds the commonly used γ-Al2O3 by achieving a stable conversion of ∼93% with a selectivity for ethylene production of ∼78% during a 17 h continuous period on stream at 240 °C.

A deprotonation pathway to reactive [B]CH2 boraalkenes.

The BH compounds IMes(ArF)BH(NTf2) (ArF: C6F5 or FpXyl) were converted to the IMes(ArF)BCH2 boraalkenes in a three step reaction sequence of B-methylation with methyllithium, hydride abstraction and deprotonation. The BCH2 boraalkenes reacted with elemental sulfur to give a thiaborirane product. They underwent [2+2] cycloaddition reactions with carbon dioxide or sulfur dioxide to give four-membered boron containing heterocycles. The boraalkenes added strongly Lewis acidic boranes at their CH2 carbon atoms. The corresponding HB(C6F5)2/boraalkene adduct reduced carbon monoxide to a -OCH(C6F5)- moiety inside a five-membered heterocycle at the B-CH2-B template. The boraalkenes reacted with the [(Me2S)AuCl] reagent to form the corresponding (boraalkene)AuCl complexes.

Synthesis and characterisation of Pd(ii) and Au(i) complexes with mesoionic carbene ligands bearing phosphinoferrocene substituents and isomeric carbene moieites.

While numerous functional ligands combining phosphine and imidazole-2-ylidene (or imidazolin-2-ylidene) donor moieties have already been reported, the chemistry of the corresponding functional mesoionic carbenes (MIC) derived from 1,2,3-triazoles remains nearly untapped. This contribution describes the synthesis of two isomeric series of triazolium salts bearing 1'-(diphenylphosphino)ferrocenyl substituents by [3 + 2] cycloaddition of a P-protected phosphinoferrocene alkyne with azides, or alternatively of a P-protected phosphinoferrocene azide with terminal alkynes, and by subsequent methylation. These salts were used to synthesize structurally unique Pd(ii) complexes featuring a P,C-chelating triazolylidene carbene ligands and Au(i)-MIC complexes with free phosphine groups. The latter were further utilised to prepare Pd(ii)Au(i) heterometallic complexes containing bridging ferrocene phosphino-carbenes as structurally flexible, donor-unsymmetric metalloligands. In addition, the reactivity of the newly prepared, P-protected phosphinoferrocene alkyne Ph2PfcC[triple bond, length as m-dash]CH·BH3 (fc = ferrocene-1,1'-diyl) was investigated, and representatives from all reported compound classes were structurally characterised.

Using the FpXylBH2•SMe2 reagent for the regioselective synthesis of cyclic bis(alkenyl)boranes.

The reactive borane reagent FpXylBH2•SMe2 was prepared from 1,4-bis(trifluoromethyl)benzene by treatment with n-BuLi, followed by H3B·SMe2 and subsequent removal of hydride. It undergoes a regioselective hydroboration reaction with 1,2-bis(trimethylsilylethynyl)benzene to give the "dimeric" product 13a featuring a conjugated 14-membered core heterocyclic structure that contains a pair of FpXylB units.

Synthesis and Structural Characterisation of an N-Phosphanyl Ferrocene Carboxamide and its Ruthenium, Rhodium and Palladium Complexes.

[((Diphenylphosphanyl)amino)carbonyl]ferrocene (1) has been synthesized and coordinated to light platinum metals, ruthenium, rhodium and palladium, in diverse coordination modes. Specifically, compound 1 was used to prepare the following phosphane complexes, [(η6 -mes)RuCl2 (1-κP)], [(η5 -C5 Me5 )RhCl2 (1-κP)], trans-[PdCl2 (1-κP)2 ], and [(LNC )PdCl(1-κP)] (mes=mesitylene, LNC =[2-(dimethylamino-κN)methyl]phenyl-κC1 ). They were subsequently converted into cationic O,P-chelate complexes by halide abstraction with AgClO4 and into neutral O,P-chelate complexes by deprotonation with potassium tert-butoxide. All coordination compounds and phosphane chalcogenides 1E (P-bound chalcogen atom E=O, S and Se), which were also synthesised, were structurally characterised using spectroscopic methods (IR, multinuclear NMR and ESI MS) and single-crystal X-ray diffraction analysis. The electrochemical behaviour of the prepared compounds was studied by cyclic voltammetry, and the (LNC )Pd-1 complexes were further studied by Mössbauer spectroscopy.

Reactions of an anionic chelate phosphane/borata-alkene ligand with [Rh(nbd)Cl]2, [Rh(CO)2Cl]2 and [Ir(cod)Cl]2.

Borata-alkenes can serve as anionic olefin equivalent ligands in transition metal chemistry. A chelate ligand of this type is described and used for metal coordination. Deprotonation of the Mes2P(CH2)2B(C6F5)2 frustrated Lewis pair in the α-CH[B] position gave the methylene-bridged phosphane/borata-alkene anion. It reacted with the [Rh(nbd)Cl] or [Rh(CO)2Cl] dimers to give the respective neutral chelate [P/C[double bond, length as m-dash]B][Rh] complexes. The reaction of the [P/C[double bond, length as m-dash]B]- anion with [Ir(cod)Cl]2 proceeded similarly, only that the complex underwent a subsequent oxidative addition reaction at the mesityl substituent. Both the resulting Ir(iii)hydride complex 15 and the P/borata-alkene Rh system 12 were used as hydrogenation catalysts. The [P/C[double bond, length as m-dash]B(C6F5)2]Rh(nbd) complex 12 served as a catalyst for arylacetylene polymerization.

Versatile coordination and C-H activation of a multi-donor phosphinoferrocene carboxamide ligand in Pd(ii) complexes.

A multi-donor phosphinoferrocene carboxamide, FcCONHCH2CH2PPh2 (1, Fc = ferrocenyl), was prepared, converted into the corresponding phosphine oxide 1O and phosphine selenide 1Se and, mainly, studied as a ligand in Pd(ii) complexes. In its native form, amide 1 preferentially coordinated soft Pd(ii) as a simple phosphine, giving rise to mixtures of cis and trans-[PdX2(1-κP)2] (2; X = Cl (a), Br (b), and I (c)), wherein the isomer ratios depended on the auxiliary halide ligand or, alternatively, to the complex [(LNC)PdCl(1-κP)] (6, LNC = 2-[(dimethylamino)methyl-κN]phenyl-κC1). This coordination mode was nevertheless easily changed when creating a vacant coordination site at the palladium. Thus, treatment of 2a with NH4[PF6] in the presence of free 1 produced [PdCl(1-κP)3][PF6] (3), while complete halogen removal with a Ag(i) salt led to cationic complexes cis-[Pd(1-κ2O,P)2]X2 (4, X = CF3SO3 (a), ClO4 (b), BF4 (c)) or [(LNC)Pd(1-κ2O,P)]X (7a and 7b), containing seven-membered O,P-chelate rings. In contrast, amide nitrogen deprotonation with KOt-Bu followed by spontaneous intramolecular halogen substitution resulted in the transformation of 6 into the chelate complex [(LNC)Pd{(1- H)-κ2N,P}] (8) featuring a five-membered N,P-chelate ring, and in the conversion of 2a and 2b into the product of C-H bond activation [Pd{Fe(η5-C5H3CONCH2CH2PPh2-κ3C,N,P)(η5-C5H5)}(1-κP)] (5), with doubly chelating deprotonated 1. Importantly, complexes 2-4-5 and 6-7-8 were mutually interconverted in triads (by protonation/deprotonation and by halide addition/abstraction), which highlights the flexible coordination and chemical stability of ligand 1. The crystal structures of 1O·½H2O, trans-2a·MeCN, trans-2b·3C2H4Cl2, trans-2c·2.5C2H4Cl2, 4a·CH2Cl2, 5·3CHCl3·Et2O, and 8 were determined by single-crystal X-ray diffraction analysis, and the representative compounds were studied by cyclic voltammetry.

Borane-induced ring closure reaction of oligomethylene-linked bis-allenes.

The trimethylene-linked bis-allene 3a reacts with Piers' borane [HB(C6F5)2] by a hydroboration/allylboration sequence to generate the cyclization product 5a. Its pyridine adduct was isolated and characterized by X-ray diffraction. Compound 5a undergoes a typical frustrated Lewis pair 1,2-P/B alkene addition reaction with PPh3 to give the heterobicyclic bridged olefinic zwitterionic product 9a. The tetramethylene-linked bis-allene 3b and its phenylene annulated analogue 3c react with HB(C6F5)2 to give the analogous seven-membered ring products 5b,c under mild conditions. The cyclization product 5a undergoes a series of sequential allylboration reactions with two equivalents of allene followed by ring-closure to give the four-component coupling product 12a. It undergoes FLP addition to an exo-methylene group upon treatment with PPh3. Compound 12a is oxidatively converted to the boron-free alcohol.

Consecutive intermolecular 1,1-carboboration reactions of Me3Si-substituted alkynes with the halogeno-B(C6F5)2 reagents.

1-(Trimethylsilyl)propyne 2a reacts with halogenoboranes XB(C6F5)2 (X: Cl, Br) in a 1 : 1 molar ratio at r.t. to give the respective alkenylboranes 3. These undergo a subsequent 1,1-alkenylboration reaction with additional alkyne 2a to give the persubstituted 3-boryl-2,4-hexadiene products 4. The conjugated diyne bis(trimethylsilyl)butadiyne 2d reacts with ClB(C6F5)2 in a 2 : 1 molar ratio by a sequence of consecutive 1,1-carboboration reactions to give the persubstituted borylated octadiendiyne product 6.

Comparing the reactivity of isomeric phosphinoferrocene nitrile and isocyanide in Pd(ii) complexes: synthesis of simple coordination compounds vs. preparation of P-chelated insertion products and Fischer-type carbenes.

Isomeric phosphinoferrocene ligands, viz. 1'-(diphenylphosphino)-1-cyanoferrocene (1) and 1'-(diphenylphosphino)-1-isocyanoferrocene (2), show markedly different coordination behaviours. For instance, the reactions of 1 with [PdCl2(MeCN)2] and [(LNC)Pd(µ-Cl)]2 (LNC = [2-(dimethylamino-κN)methyl]phenyl-κC1) produced the "phosphine" complexes [PdCl2(1-κP)2] (7) and [(LNC)PdCl(1-κP)] (8), and the latter was converted into the coordination polymer [(LNC)Pd(µ(P,N)-1)][SbF6] (9). Conversely, the reaction of 2 with [(LNC)Pd(µ-Cl)]2 involved coordination of the phosphine moiety and simultaneous insertion of the isocyanide group into the Pd-C bond, giving rise to the P,η1-imidoyl complex [PdCl(Ph2PfcN[double bond, length as m-dash]CC6H4CH2NMe2-κ3C,N,P)] (10; fc = ferrocene-1,1'-diyl). Compound 10 was further transformed into the Fischer carbene [PdCl(Ph2PfcN(Me)CC6H4CH2NMe2-κ3P,C,N)][BF4] (11) by methylation with [Me3O][BF4]. The reactions of 2 with Pd-Me and Pd(η3-allyl) precursors also led to imidoyl complexes [Pd(µ-Cl)(Ph2PfcN[double bond, length as m-dash]CR-κ2C,P)]2 (R = Me: 12, R = allyl: 15), which were cleaved with PPh3 into the corresponding monopalladium complexes [PdCl(PPh3)(Ph2PfcN[double bond, length as m-dash]CR-κ2C,P)] (R = Me: 13, R = allyl: 16). The treatment of 12 and 15 with thallium(i) acetylacetonate (acac) produced [Pd(acac-O,O')(Ph2PfcN[double bond, length as m-dash]CR-κ2C,P)] (R = Me: 17, R = allyl: 18). Through proton transfer, these complexes reacted with Ph2PCH2CO2H, ultimately producing bis-chelate complexes [Pd(Ph2PCH2CO2-κ2O,P)(Ph2PfcN[double bond, length as m-dash]CR)] (R = Me: 19, R = prop-1-enyl (sic!): 20). In addition, compound 13 was converted into the P-chelated carbene [PdCl(PPh3)(Ph2PfcN(Me)CMe-κ2C,P)][BF4] (14). Compounds 10, 11, 13 and 14 were studied by cyclic voltammetry and by DFT computations.