Vincenzo Mirabello

Experimental Evidence of Phosphine Oxide Generation in Solution and Trapping by Ruthenium Complexes

Phosphorus oxides, oxyacids, and their esters are important chemicals for industry. Apart from playing a role in most organisms in ruling their energy transformations, they find wide and diverse applications, such as fertilizers, pesticides, herbicides, lubricants, flame retardants, additives for special plastics and materials, and drugs for different diseases. Little attention has however been paid to lower-oxidation-state species, such as PO, HPO, and P2O, for which synthetic isolation procedures and even direct evidence of their existence are scarce. One of the most elusive species in this regard is phosphine oxide, H3PO (I ; Scheme 1). This molecule was first observed by reacting atomic oxygen with PH3 using a discharge–flow system equipped with molecularbeam sampling mass spectrometry. Alternatively, red-light photolysis of co-deposited PH3/O3 onto an argon matrix at 12–18 K was used to generate and trap I in a very diluted concentration together with its tautomer phosphinous acid H2P(OH) (II), which was identified by FTIR. [4] Finally, Ault and Kayser observed the formation of H3PO in argon matrices after photochemical irradiation of a mixture of VOCl3, CrO2Cl2, and PH3. [5] Both molecules have been studied by theoretical methods. Application of an adequate phosphorus basis set has recently shown that, in contrast with previous ab initio studies, I is more stable than II by only about 1 kcalmol 1 in the gas phase. In contrast, computational analysis in aqueous solution showed that upon solvation I is largely preferred by about 10 kcal mol 1 owing to stronger hydrogen bonding with the highly polar P!O bond. The possible involvement of H3PO in the oxidative polymerization of phosphine to give polyhydride phosphorus PxHy polymers has been also proposed. Herein we show that the previously unknown P I species H3PO (I) can be easily generated in solution by electrochemical methods, and we provide evidence of its solution stability, its characterization by conventional NMR spectroscopy, and its trapping as a ligand in the coordination sphere of hydrosoluble ruthenium complexes after tautomerization to II. The electrochemical generation of H3PO was performed in a single electrochemical cell with a lead cathode and a sacrificial zinc anode using P4 melted in a slightly acidic water/ ethanol solution (2:1 volume ratio, water acidified with HCl, 2m) at 60 8C (Supporting Information, Figures S1, S2). The overall electrochemical process may be divided in two parts. In the first step, the electrochemical generation of PH3 on the lead cathode takes place as previously described, 11] while in the second step, mild oxidation of PH3 to H3PO occurs at the anodic surface of the zinc electrode. In agreement with cyclic voltammetry experiments showing an irreversible oxidation wave, PH3 is electrochemically active in the anodic potential range + 0.80–1.25 V (vs. Ag/AgNO3, 0.01m in CHCN3) and can be therefore oxidized in acidic water/ethanol 2:1 solution to H3PO (Supporting Information, Figure S3). Scheme 2 shows the overall electrochemical process resulting in the cathodic reduction of P4 to PH3 and anodic oxidation of PH3 to H3PO (E = + 1.24 V vs. Ag/AgNO3, 0.01m in CHCN3). Different working conditions were investigated to optimize the production of H3PO. The best performance was Scheme 1. Phosphine oxide (I) and its tautomer, phosphinous acid (II).

Solution and Solid-State Dynamics of Metal-Coordinated White Phosphorus

The dynamic behavior in solution of eight mono-hapto tetraphosphorus transition metal-complexes, trans-[Ru(dppm)(2)(H)(η(1)-P(4))]BF(4) ([1]BF(4)), trans-[Ru(dppe)(2)(H)(η(1)-P(4))]BF(4) ([2]BF(4)), [CpRu(PPh(3))(2)(η(1)-P(4))]PF(6) ([3]PF(6)), [CpOs(PPh(3))(2)(η(1)-P(4))]PF(6) ([4]PF(6)), [Cp*Ru(PPh(3))(2)(η(1)-P(4))]PF(6) ([5]PF(6)), [Cp*Ru(dppe)(η(1)-P(4))]PF(6) ([6]PF(6)), [Cp*Fe(dppe)(η(1)-P(4))]PF(6) ([7]PF(6)), [(triphos)Re(CO)(2)(η(1)-P(4))]OTf ([8]OTf), and of three bimetallic Ru(μ,η(1:2)-P(4))Pt species [{Ru(dppm)(2)(H)}(μ,η(1:2)-P(4)){Pt(PPh(3))(2)}]BF(4) ([1-Pt]BF(4)), [{Ru(dppe)(2)(H)}(μ,η(1:2)-P(4)){Pt(PPh(3))(2)}]BF(4) ([2-Pt]BF(4)), [{CpRu(PPh(3))(2))}(μ,η(1:2)-P(4)){Pt(PPh(3))(2)}]BF(4) ([3-Pt]BF(4)), [dppm=bis(diphenylphosphanyl)methane; dppe=1,2-bis(diphenylphosphanyl)ethane; triphos=1,1,1-tris(diphenylphosphanylmethyl)ethane; Cp=η(5)-C(5)H(5); Cp*=η(5)-C(5)Me(5) ] was studied by variable-temperature (VT) NMR and (31)P{(1)H} exchange spectroscopy (EXSY). For most of the mononuclear species, NMR spectroscopy allowed to ascertain that the metal-coordinated P(4) molecule experiences a dynamic process consisting, apart from the free rotation about the M-P(4) axis, in a tumbling movement of the P(4) cage while remaining chemically coordinated to the central metal. EXSY and VT (31)P NMR experiments showed that also the binuclear complex cations [1-Pt](+)-[3-Pt](+) are subjected to molecular motions featured by the shift of each metal from one P to an adjacent one of the P(4) moiety. The relative mobility of the metal fragments (Ru vs. Pt) was found to depend on the co-ligands of the binuclear complexes. For complexes [2]BF(4) and [3]PF(6), MAS, (31)P NMR experiments revealed that the dynamic processes observed in solution (i.e., rotation and tumbling) may take place also in the solid state. The activation parameters for the dynamic processes of complexes 1(+), 2(+), 3(+), 4(+), 6(+), 8(+) in solution, as well as the X-ray structures of 2(+), 3(+), 5(+), 6(+) are also reported. The data collected suggest that metal-coordinated P(4) should not be considered as a static ligand in solution and in the solid state.

Fluorescence-Lifetime Imaging and Super-Resolution Microscopies Shed Light on the Directed- and Self-Assembly of Functional Porphyrins onto Carbon Nanotubes and Flat Surfaces

Abstract Functional porphyrins have attracted intense attention due to their remarkably high extinction coefficients in the visible region and potential for optical and energy‐related applications. Two new routes to functionalised SWNTs have been established using a bulky ZnII‐porphyrin featuring thiolate groups at the periphery. We probed the optical properties of this zinc(II)‐substituted, bulky aryl porphyrin and those of the corresponding new nano‐composites with single walled carbon nanotube (SWNTs) and coronene, as a model for graphene. We report hereby on: i) the supramolecular interactions between the pristine SWNTs and ZnII‐porphyrin by virtue of π–π stacking, and ii) a novel covalent binding strategy based on the Bingel reaction. The functional porphyrins used acted as dispersing agent for the SWNTs and the resulting nanohybrids showed improved dispersibility in common organic solvents. The synthesized hybrid materials were probed by various characterisation techniques, leading to the prediction that supramolecular polymerisation and host–guest functionalities control the fluorescence emission intensity and fluorescence lifetime properties. For the first time, XPS studies highlighted the differences in covalent versus non‐covalent attachments of functional metalloporphyrins to SWNTs. Gas‐phase DFT calculations indicated that the ZnII‐porphyrin interacts non‐covalently with SWNTs to form a donor–acceptor complex. The covalent attachment of the porphyrin chromophore to the surface of SWNTs affects the absorption and emission properties of the hybrid system to a greater extent than in the case of the supramolecular functionalisation of the SWNTs. This represents a synthetic challenge as well as an opportunity in the design of functional nanohybrids for future sensing and optoelectronic applications.

Stabilization of the Triphosphallyl Ligand η3‐P3{P(O)H} at Iridium via Alkaline Activation of P4

The selective functionalization of the polyphosphorus moiety Ph2PCH2PPh2PPPP present as a tetrahapto-ligand in complex [Ir(dppm)(Ph2PCH2PPh2PPPP)](+) (1, dppm=Ph2PCH2PPh2) was obtained by reaction of 1 with water under basic conditions at room temperature. The formation of the new triphosphaallyl moiety η(3)-P3{P(O)H} was determined in solution by NMR spectroscopy, and confirmed in the solid state by a single-crystal X-ray structure of the stable product [Ir(κ(2)-dppm)(κ(1)-dppm)(η(3)-P3{P(O)H})] (2). In solution, 2 has a fluxional behavior attributable to the four P atoms belonging to the tetraphosphorus moiety in 1 and exhibits a chemical exchange process involving the two PPh2 moieties of the same bidentate ligand, as determined by 1D and 2D NMR spectroscopy experiments carried out at variable temperature. The mechanism of the reaction was investigated at the DFT level, which suggested a selective attack of an in-situ generated OH(-) anion on one of the non-coordinated phosphorus atoms of the P4 moiety. The reaction then evolves through an acid-assisted tautomerization, which leads to the final compound 2. Bonding analysis pointed out that the new unsubstituted P3-unit in the η(3)-P3{P(O)H} moiety behaves as a triphosphallyl ligand.

Oxygen Sensing, Hypoxia Tracing and in Vivo Imaging with Functional Metalloprobes for the Early Detection of Non-communicable Diseases

Hypoxia has been identified as one of the hallmarks of tumor environments and a prognosis factor in many cancers. The development of ideal chemical probes for imaging and sensing of hypoxia remains elusive. Crucial characteristics would include a measurable response to subtle variations of pO2 in living systems and an ability to accumulate only in the areas of interest (e.g., targeting hypoxia tissues) whilst exhibiting kinetic stabilities in vitro and in vivo. A sensitive probe would comprise platforms for applications in imaging and therapy for non-communicable diseases (NCDs) relying on sensitive detection of pO2. Just a handful of probes for the in vivo imaging of hypoxia [mainly using positron emission tomography (PET)] have reached the clinical research stage. Many chemical compounds, whilst presenting promising in vitro results as oxygen-sensing probes, are facing considerable disadvantages regarding their general application in vivo. The mechanisms of action of many hypoxia tracers have not been entirely rationalized, especially in the case of metallo-probes. An insight into the hypoxia selectivity mechanisms can allow an optimization of current imaging probes candidates and this will be explored hereby. The mechanistic understanding of the modes of action of coordination compounds under oxygen concentration gradients in living cells allows an expansion of the scope of compounds toward in vivo applications which, in turn, would help translate these into clinical applications. We summarize hereby some of the recent research efforts made toward the discovery of new oxygen sensing molecules having a metal-ligand core. We discuss their applications in vitro and/or in vivo, with an appreciation of a plethora of molecular imaging techniques (mainly reliant on nuclear medicine techniques) currently applied in the detection and tracing of hypoxia in the preclinical and clinical setups. The design of imaging/sensing probe for early-stage diagnosis would longer term avoid invasive procedures providing platforms for therapy monitoring in a variety of NCDs and, particularly, in cancers.

Synthesis, radiolabelling and in vitro imaging of multifunctional nanoceramics

Abstract Molecular imaging has become a powerful technique in preclinical and clinical research aiming towards the diagnosis of many diseases. In this work, we address the synthetic challenges in achieving lab‐scale, batch‐to‐batch reproducible copper‐64‐ and gallium‐68‐radiolabelled metal nanoparticles (MNPs) for cellular imaging purposes. Composite NPs incorporating magnetic iron oxide cores with luminescent quantum dots were simultaneously encapsulated within a thin silica shell, yielding water‐dispersible, biocompatible and luminescent NPs. Scalable surface modification protocols to attach the radioisotopes 64Cu (t1/2=12.7 h) and 68Ga (t1/2=68 min) in high yields are reported, and are compatible with the time frame of radiolabelling. Confocal and fluorescence lifetime imaging studies confirm the uptake of the encapsulated imaging agents and their cytoplasmic localisation in prostate cancer (PC‐3) cells. Cellular viability assays show that the biocompatibility of the system is improved when the fluorophores are encapsulated within a silica shell. The functional and biocompatible SiO2 matrix represents an ideal platform for the incorporation of 64Cu and 68Ga radioisotopes with high radiolabelling incorporation.

Carbon Nanotubes and Related Nanohybrids Incorporating Inorganic Transition Metal Compounds and Radioactive Species as Synthetic Scaffolds for Nanomedicine Design:Chapter Eight

Molecular imaging and applications of nanotechnology in health care are interlinked research areas that are currently of high strategic importance to Europe and worldwide. In this sense, there is great current interest in understanding behavior in cells for target-specific pharmaceuticals assembled for the early detection and therapy of diseases (ranging from cancer to cardiovascular and neurodegenerative diseases). To date, little is understood about the most effective way to assemble and deliver in a targeted manner multimodal contrast agents (here defined as “all in one” imaging probes incorporating metals and metal complexes leading to optical/radiopharmaceuticals and/or paramagnetic nanomaterials) necessary to achieve high-resolution images of processes taking place in cells and tissues, the mechanisms of their uptake in cells and tissues, and the effect that these functional imaging tools have on the targeted cells and tissues. In particular, limited information exists regarding the mechanisms of interactions between functional carbon nanomaterials as new inorganic material-based nanodiagnostics and therapeutic agents for imaging and therapy in diagnostic medicine and cells. A major aspect of this overview that has been virtually unexplored to date in current literature is to rationalize and evaluate the nature and strength of connections among different components of the probe, and to comment on the likely impact on the overall biological functionalities, which is necessary before evaluating their interactions with living systems. In this chapter, different and perhaps unconventional approaches to developing a test-informed protocol for constructing complete bioimaging probes (incorporating inorganic and organometallic transition metal complexes and carbon nanomaterial scaffolds) and testing their functionalities in cells are highlighted. Some approaches to testing and monitoring the delivery, cytotoxicity, and uptake of mechanisms of bioimaging probes assembled on single-walled carbon nanotube scaffolds into a variety of healthy and diseased cells of the complete probes are reviewed. These may be localized on the cells’ surface or inside the cells when derivatized with a targeting group or self-targeted (without a tagged targeting unit).

A straightforward access to ruthenium-coordinated fluorophosphines from phosphorous oxyacids

The transformation of phosphorous oxyacids into the corresponding fluorophosphines was mediated by [RuCp(PPh3)2Cl] under mild reaction conditions using a soft deoxofluorinating agent. The reaction is selective, proceeds with high yields and can be extended to a wide range of phosphorous oxyacids once coordinated to the ruthenium synthon [RuCp(PPh3)2](+) as their hydroxyphosphine tautomer. Deoxofluorination of phenylphosphinic acid was also mediated by [RuCp(R)(CH3CN)3]PF6, where Cp(R): Cp = C5H5, Cp* = C5Me5, and [Ru(η(6)-p-cymene)(μ-Cl)Cl]2. X-Ray single crystal structures of the two new derivatives, [RuCp(PPh3)2{PhP(OH)2}]CF3SO3 and [Ru(η(6)-p-cymene)Cl2{PhP(OH)2}] have been determined.

Encapsulation of cadmium selenide nanocrystals in biocompatible nanotubes: DFT calculations, X-ray diffraction investigations and confocal fluorescence imaging

Abstract The encapsulation of CdSe nanocrystals within single‐walled carbon nanotube (SWNT) cavities of varying dimensions at elevated temperatures under strictly air‐tight conditions is described for the first time. The structures of CdSe nanocrystals under confinement inside SWNTs was established in a comprehensive study, combining both experimental and DFT theoretical investigations. The calculated binding energies show that all considered polymorphs [(3:3), (4:4), and (4:2)] may be obtained experimentally. The most thermodynamically stable structure (3:3) is directly compared to the experimentally observed CdSe structures inside carbon nanotubes. The gas‐phase DFT‐calculated energy difference between “free” 3:3 and 4:2 structures (whereby 3:3 models a novel tubular structure in which both Cd and Se form three coordination, as observed experimentally for HgTe inside SWNT, and 4:2 is a motif derived from the hexagonal CuI bulk structure in which both Cd and Se form 4 or 2 coordination) is surprisingly small, only 0.06 eV per formula unit. X‐ray powder diffraction, Raman spectroscopy, high‐resolution transmission electron microscopy, and energy‐dispersive X‐ray analyses led to the full characterization of the SWNTs filled with the CdSe nanocrystals, shedding light on the composition, structure, and electronic interactions of the new nanohybrid materials on an atomic level. A new emerging hybrid nanomaterial, simultaneously filled and beta‐d‐glucan coated, was obtained by using pristine nanotubes and bulk CdSe powder as starting materials. This displayed fluorescence in water dispersions and unexpected biocompatibility was found to be mediated by beta‐d‐glucan (a biopolymer extracted from barley) with respect to that of the individual inorganic material components. For the first time, such supramolecular nanostructures are investigated by life‐science techniques applied to functional nanomaterial characterization, opening the door for future nano‐biotechnological applications.