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Over the past decade, porphyrin derivatives have emerged as invaluable synthetic building blocks and theranostic kits for the delivery of cellular fluorescence imaging and photodynamic therapy. Tetraphenylporphyrin (TPP), its metal complexes, and related derivatives have been investigated for their use as dyes in histology and as components of multimodal imaging probes. The photophysical properties of porphyrin-metal complexes featuring radiometals have been a focus of our attention for the realization of fluorescence imaging probes coupled with radioimaging capabilities and therapeutic potential having "true" theranostic promise. We report hereby on the synthesis, radiochemistry, structural investigations, and preliminary in vitro and in vivo uptake studies on a range of functionalized porphyrin-based derivatives. In pursuit of developing new porphyrin-based probes for multimodality imaging applications, we report new functionalized neutral, polycationic, and polyanionic porphyrins incorporating nitroimidazole and sulfonamide moieties, which were used as targeting groups to improve the notoriously poor pharmacokinetics of porphyrin tags. The resulting functional metalloporphyrin species were stable under serum challenges and the nitroimidazole and sulfonamide derivatives remained fluorescent, allowing in vitro confocal studies and visualization of the lysosomal uptake in a gallium(III) sulfonamide derivative. The molecular structures of selected porphyrin derivatives were determined by single crystal X-ray diffraction using synchrotron radiation. We also investigated the nature of the emission/excitation behavior of model functional porphyrins using in silico approaches such as TD DFT in simple solvation models. The conjugation of porphyrins with the [7-13] and [7-14] fragments of bombesin was also achieved, to provide targeting of the gastrin releasing peptide receptor (GRPR). Depending on the metal, probe conjugates of relevance for single photon emission computed tomography (SPECT) or positron emission tomography (PET) probes have been designed and tested hereby, using TPP and related functional free base porphyrins as the bifunctional chelator synthetic scaffold and 111In[In] or 68Ga[Ga], respectively, as the central metal ions. Interestingly, for simple porphyrin conjugates good radiochemical incorporation was obtained for both radiometals, but the presence of peptides significantly diminished the radio-incorporation yields. Although the gallium-68 radiochemistry of the bombesin conjugates did not show radiochemical incorporation suitable for in vivo studies, likely because the presence of the peptide changed the behavior of the TPP-NH2 synthon taken alone, the optical imaging assays indicated that the conjugated peptide tags do mediate uptake of the porphyrin units into cells.

We report on the design and testing of new graphite and graphene oxide‐based extended π‐conjugated synthetic scaffolds for applications in sustainable chemistry transformations. Nanoparticle‐functionalised carbonaceous catalysts for new Fischer Tropsch and Reverse GasWater Shift (RGWS) transformations were prepared: functional graphene oxides emerged from graphite powders via an adapted Hummer's method and subsequently impregnated with uniform‐sized nanoparticles. Then the resulting nanomaterials were imaged by TEM, SEM, EDX, AFM and characterised by IR, XPS and Raman spectroscopies prior to incorporation of Pd(II) promoters and further microscopic and spectroscopic analysis. Newly synthesised 2D and 3D layered nanostructures incorporating carbon‐supported iron oxide nanoparticulate pre‐catalysts were tested, upon hydrogen reduction in situ, for the conversion of CO2 to CO as well as for the selective formation of CH4 and longer chain hydrocarbons. The reduction reaction was also carried out and the catalytic species isolated and fully characterised. The catalytic activity of a graphene oxide‐supported iron oxide pre‐catalyst converted CO2 into hydrocarbons at different temperatures (305, 335, 370 and 405 °C), and its activity compared well with that of the analogues supported on graphite oxide, the 3‐dimensional material precursor to the graphene oxide. Investigation into the use of graphene oxide as a framework for catalysis showed that it has promising activity with respect to reverse gas water shift (RWGS) reaction of CO2 to CO, even at the low levels of catalyst used and under the rather mild conditions employed at atmospheric pressure. Whilst the γ‐Fe2O3 decorated graphene oxide‐based pre‐catalyst displays fairly constant activity up to 405 °C, it was found by GC‐MS analysis to be unstable with respect to decomposition at higher temperatures. The addition of palladium as a promoter increased the activity of the iron functionalised graphite oxide in the RWGS. The activity of graphene oxide supported catalysts was found to be enhanced with respect to that of iron‐functionalised graphite oxide with, or without palladium as a promoter, and comparable to that of Fe@carbon nanotube‐based systems tested under analogous conditions. These results display a significant step forward for the catalytic activity estimations for the iron functionalised and rapidly processable and scalable graphene oxide. The hereby investigated phenomena are of particular relevance for the understanding of the intimate surface morphologies and the potential role of non‐covalent interactions in the iron oxide‐graphene oxide networks, which could inform the design of nano‐materials with performance in future sustainable catalysis applications.

[EN] The gallium-68 radiolabelling of new functional graphene oxide composites is reported herein along with kinetic stability investigations of the radio-nanohybrids under different environments and insights into their surface characteristics by SEM and XPS. The present work highlights the potential of graphene oxides as nanocarriers for small molecules such as bis (thiosemicarbazonato) complexes to act as multifunctional platforms for rapid and effective radioimaging agent incorporation., The S. I. P. group thanks the Centre for Doctoral Training in Sustainable Chemical Technologies (EP/L016354/1). SIP also acknowledges the EU funding through the ERC for the Consolidator Grant O2SENSE (617107, 2014–2020). The authors thank EPSRC National Service for Mass Spectrometry at Swansea and for data collection. We thank Professor Stan Botchway for training in confocal fluorescence microscopy and Professor Jon Dilworth for helpful discussions in the radiochemistry of bis (thiosemicarbazones). The EOA group acknowledges support from Imperial College NIHR Biomedical Research Centre, Cancer Research UK (C2536/A16584) and the UK Medical Research Council (MR/J007986/1). D. G. C. also acknowledges the Fundación General CSIC (ComFuturo Program) for the financial support and F. J. P. the Spanish Ministry of Economy and Competitiveness (MINECO) (MAT2016-80394-R).

Prostate cancer has a high incidence in men and remains the second cause of mortality due to cancer worldwide. As the development of the disease is greatly correlated to age, the identification of novel detection methods reliable, efficient, and cost effective is a matter of significant importance in the ageing population of western societies. The detection of the prostate specific antigen (PSA) in blood samples has been the preferred method for the detection and monitoring of prostate cancer over the past decades. Despite the indications against its use in massive population screening, PSA still remains the best studied biomarker for prostate cancer and the detection of its different forms and incorporation in multiplexed designs with other biomarkers still remains a highly valuable indicator in the theranostics of prostate cancer. The latest developments in the use of nanomaterials towards the construction of PSA biosensors are reviewed hereby. The incorporation of gold nanoparticles, silica nanoparticles and graphene nanostructures to biosensing devices has represented a big leap forward in terms of sensitivity, stability and miniaturization. Both electrochemical and optical detection methods for the detection of PSA will be reviewed herein.

A prototype peptide-based probe has been developed for the determination of intracellular heme levels., Heme plays a vital role in cell biology and dysregulation of heme levels is implicated in a wide range of diseases. However, monitoring heme levels in biological systems is currently not straightforward. A short synthetic peptide probe containing 7-azatryptophan is shown to bind hemin in vitro with quenching of the azatryptophan fluorescence. This chemical tool can be used to detect the change in free heme induced in human skin cells upon exposure to UVA irradiation.

Existing fluorescent labels used in life sciences are based on organic compounds with limited lifetime or on quantum dots which are either expensive or toxic and have low kinetic stability in biological environments. To address these challenges, luminescent nanomaterials have been conceived as hierarchical, core-shell structures with spherical morphology and highly controlled dimensions. These tailor-made nanophosphors incorporate Ln:YVO4 nanoparticles (Ln = Eu(III) and Er(III)) as 50 nm cores and display intense and narrow emission maxima centered at ∼565 nm. These cores can be encapsulated in silica shells with highly controlled dimensions as well as functionalized with chitosan or PEG5000 to reduce nonspecific interactions with biomolecules in living cells. Confocal fluorescence microscopy in living prostate cancer cells confirmed the potential of these platforms to overcome the disadvantages of commercial fluorophores and their feasibility as labels for multiplexing, biosensing, and imaging in life science assays.

Metallic nanoparticles have been a matter of intense exploration within the last decade due to their potential to change the face of the medical world through their role as ‘nanotheranostics’. Their envisaged capacity to act as synthetic platforms for a multimodal imaging approach to diagnosis and treatment of degenerative diseases, including cancer, remains a matter of lively debate. Certain synthetic metal-based nanomaterials, e.g. gold and iron oxide nanoparticles, are already in clinical use or under advanced preclinical investigations following in vitro and in vivo preclinical imaging success. We surveyed the recent publications landscape including those reported metallic nanoparticles having established applications in vivo, as well as some of the new metallic nanoparticles which, despite their potential as cancer nanodiagnostics, are currently awaiting in vivo evaluation. The objective of this review is to highlight the current metallic nanoparticles and/or alloys as well as their derivatives with multimodal imaging potential, focusing on their chemistry as a springboard to discussing their role in the future of nanomedicines design. We also highlight here some of the fundamentals of molecular and nano-imaging techniques of relevance to the metal-based colloids, alloys and metallic nanoparticles discerning their future prospects as cancer nanodiagnostics. The current approaches for metallic and alloy surface derivatisation, aiming to achieve functional and biocompatible materials for multimodal bioimaging applications, are discussed in order to bring about some new perspectives on the efficiency of metallic nanoparticles as synthetic scaffolds for imaging probe design and forecast their future use in medical imaging techniques (optical, CT, PET, SPECT and MRI).

We report on the design and testing of new graphite and graphene oxide‐based extended π‐conjugated synthetic scaffolds for applications in sustainable chemistry transformations. Nanoparticle‐functionalised carbonaceous catalysts for new Fischer Tropsch and Reverse GasWater Shift (RGWS) transformations were prepared: functional graphene oxides emerged from graphite powders via an adapted Hummer's method and subsequently impregnated with uniform‐sized nanoparticles. Then the resulting nanomaterials were imaged by TEM, SEM, EDX, AFM and characterised by IR, XPS and Raman spectroscopies prior to incorporation of Pd(II) promoters and further microscopic and spectroscopic analysis. Newly synthesised 2D and 3D layered nanostructures incorporating carbon‐supported iron oxide nanoparticulate pre‐catalysts were tested, upon hydrogen reduction in situ, for the conversion of CO2 to CO as well as for the selective formation of CH4 and longer chain hydrocarbons. The reduction reaction was also carried out and the catalytic species isolated and fully characterised. The catalytic activity of a graphene oxide‐supported iron oxide pre‐catalyst converted CO2 into hydrocarbons at different temperatures (305, 335, 370 and 405 °C), and its activity compared well with that of the analogues supported on graphite oxide, the 3‐dimensional material precursor to the graphene oxide. Investigation into the use of graphene oxide as a framework for catalysis showed that it has promising activity with respect to reverse gas water shift (RWGS) reaction of CO2 to CO, even at the low levels of catalyst used and under the rather mild conditions employed at atmospheric pressure. Whilst the γ‐Fe2O3 decorated graphene oxide‐based pre‐catalyst displays fairly constant activity up to 405 °C, it was found by GC‐MS analysis to be unstable with respect to decomposition at higher temperatures. The addition of palladium as a promoter increased the activity of the iron functionalised graphite oxide in the RWGS. The activity of graphene oxide supported catalysts was found to be enhanced with respect to that of iron‐functionalised graphite oxide with, or without palladium as a promoter, and comparable to that of Fe@carbon nanotube‐based systems tested under analogous conditions. These results display a significant step forward for the catalytic activity estimations for the iron functionalised and rapidly processable and scalable graphene oxide. The hereby investigated phenomena are of particular relevance for the understanding of the intimate surface morphologies and the potential role of non‐covalent interactions in the iron oxide‐graphene oxide networks, which could inform the design of nano‐materials with performance in future sustainable catalysis applications., New functional two‐dimensional (2D) and three‐dimensional (3D) nanomaterials relevant for sustainable chemistry applications have been designed and tested. This work is of relevance to enhancing our understanding of the role of supramolecular aggregation on nanotechnology and on optimised designs for future materials for energy conversion/storage as a basis for the reverse gas water shift reaction and Fischer Tropsch chemistry.

The electronically saturated and air-stable complexes [Ni(η5-C5H5)(Mes-BIAN)][PF6] (1) and [Ni(η5-C5H5)(Mes-DAD)][PF6] (2) were found to behave as efficient catalyst precursors for the polymerisation of ethylene under mild reaction conditions (temperature and pressure), when activated with excess AlEt2Cl (DEAC), exhibiting activities in the range 4 × 104 to 22 × 104 g PE (mol Ni)−1 h−1 bar−1. Compound 2 was synthesised and fully characterised as reported hereby for the first time, and exhibits a catalytic activity of ca. 30 × 104 g PE (mol Ni)−1 h−1 bar−1 in the polymerisation of ethylene. The reactivity of these complexes towards DEAC was found to lead to the formation of diamagnetic cationic Ni(II) complexes (4 and 3, respectively) containing the same initial cation [Ni(η5-C5H5)(α-diimine)]+ and an [AlEtCl3]− anion, whereby diimine = BIAN (1 and 4) and DAD (2 and 3). In the corresponding reaction of complex [Ni(η5-C5H5)(Mes-BIAN)][PF6] (1), an unusual paramagnetic complex incorporating a cationic trinuclear α-diimine Ni cluster (5), containing five bridging Cl ligands and an [AlCl4]− anion, was also isolated and fully characterised, in which the cyclopentadienyl ligand was absent. The intermediates 3 and 5 catalysed efficiently the polymerisation of ethylene when the DEAC cocatalyst was used in slight excess. The polyethylene produced (ca. 10 × 104 to 30 × 104 g PE (mol Ni)−1 h−1 bar−1, respectively) showed branching numbers ranging from 7 to 75 branches per 1000 carbon atoms according to 1H NMR spectroscopy analysis. These findings are surprising given that the new 18-electron nickel precursors show remarkable properties towards ethylene polymerisation catalysis when activated with a small amount of aluminium activator under mild conditions, and also that some unusual intermediates responsible for the observed activity were isolated and characterised by X-ray crystallography.

A naphthalimide-based chemosensing motif turns ON the fluorescence emission in solution in the presence of aqueous iron(III) chloride, and maintains this property in living cancer cells. The emission response to Fe(III) ions occurs simultaneously with a change in pH. The protonation of methyl piperazine-conjugated naphthalimide promotes its lysosomal localisation as assessed by co-localisation tests and fluorescence lifetime imaging microscopy (FLIM) in vitro.

Reaction between lithium indenyl and a chlorine substituted alpha diimine of the form [{Cl(NPh)2}C)]2 unexpectedly yielded the corresponding NH rearranged derivative [PhN(H)C(C9H6)]2 (1) rather than the predicted symmetrical α-diimine. This compound 1 was characterised by 1H NMR, 13C{1H} NMR and mass spectrometry, and additionally by X-ray diffraction. It was found that 1 was the first indene-substituted and symmetric secondary amine which was also highly fluorescent in DMSO. The reactivity of 1 towards simple inorganic and organometallic transition metals precursors based on the MX2 fragments, where M = Group 10 metals and X = halides or methyl groups, has been investigated. Surprisingly, the reaction with [PtMe2(COD)] led to the coupling reaction between the indenyl groups incorporated at the C-C ligand backbone and a new ligand (2) was discovered, in an attempt to synthesise the metal-linked diamine. Single crystal X-ray diffraction studies confirm this compound 2 to feature coupled indenyl residues and delocalised C-C bonds in the solid state. Structural authentication by X-ray crystallography showed compound 2 to be a very rare example of flat and extended aromatic organic molecule and mass spectrometry, IR and NMR spectroscopy were carried out to gain further insight into the solid state and solution phase structures. Further experiments to synthesise analogues of [PhN(H)C(Ind)]2 aiming to shift a likely equilibrium in favour the imine tautomer, by introducing bulky ortho substituents onto the benzene ring (R = Me, iPr) showed the presence of the imine tautomer to be increasingly favoured in 1H NMR spectra, with an increase in the steric bulk of the ortho substituents. However, the enamine tautomer is still observed to a minor extent even with isopropyl substituents and yields of these desired compounds were low on steric grounds.

Three‐dimensional fluorescent graphene frameworks with controlled porous morphologies are of significant importance for practical applications reliant on controlled structural and electronic properties, such as organic electronics and photochemistry. Here we report a synthetically accessible approach concerning directed aromatic stacking interactions to give rise to new fluorogenic 3D frameworks with tuneable porosities achieved through molecular variations. The binding interactions between the graphene‐like domains present in the in situ‐formed reduced graphene oxide (rGO) with functional porphyrin molecules lead to new hybrids via an unprecedented solvothermal reaction. Functional free‐base porphyrins featuring perfluorinated aryl groups or hexyl chains at their meso‐ and β‐positions were employed in turn to act as directing entities for the assembly of new graphene‐based and foam‐like frameworks and of their corresponding coronene‐based hybrids. Investigations in the dispersed phase and in thin‐film by XPS, SEM and FLIM shed light onto the nature of the aromatic stacking within functional rGO frameworks (denoted rGOFs) which was then modelled semi‐empirically and by DFT calculations. The pore sizes of the new emerging reduced graphene oxide hybrids are tuneable at the molecular level and mediated by the bonding forces with the functional porphyrins acting as the “molecular glue”. Single crystal X‐ray crystallography described the stacking of a perfluorinated porphyrin with coronene, which can be employed as a molecular model for understanding the local aromatic stacking order and charge transfer interactions within these rGOFs for the first time. This opens up a new route to controllable 3D framework morphologies and pore size from the Ångstrom to the micrometre scale. Theoretical modelling showed that the porosity of these materials is mainly due to the controlled inter‐planar distance between the rGO, coronene or graphene sheets. The host‐guest chemistry involves the porphyrins acting as guests held through π‐π stacking, as demonstrated by XPS. The objective of this study is also to shed light into the fundamental localised electronic and energy transfer properties in these new molecularly engineered porous and fluorogenic architectures, aiming in turn to understand how functional porphyrins may exert stacking control over the notoriously disordered local structure present in porous reduced graphene oxide fragments. By tuning the porosity and the distance between the graphene sheets using aromatic stacking with porphyrins, it is also possible to tune the electronic structure of the final nanohybrid material, as indicated by FLIM experiments on thin films. Such nanohybrids with highly controlled pores dimensions and morphologies open the way to new design and assembly of storage devices and applications incorporating π‐conjugated molecules and materials and their π‐stacks may be relevant towards selective separation membranes, water purification and biosensing applications., By introducing a panel of functional porphyrin molecules, new 3D hierarchical structures incorporating reduced graphene oxide can be achieved. The pore size of the framework can be finely tuned and reduced to a sub‐micron scale for the first time by careful selection of the porphyrin. Experimental and theoretical studies proposed that the pore size diminishing was due to strong local interactions between the designed porphyrin and rGO, mediated by donor‐acceptor interactions, which are maintained in the solution and in thin film.

Although prostate cancer is one of the most common cancers in the male population, its basic biological function at a cellular level remains to be fully understood. This lack of in depth understanding of its physiology significantly hinders the development of new, targeted and more effective treatment strategies. Whilst electrophysiological studies can provide in depth analysis, the possibility of recording electrical activity in large populations of non-neuronal cells remains a significant challenge, even harder to address in the picoAmpere-range, which is typical of cellular level electrical activities. In this paper, we present the measurement and characterization of electrical activity of populations of prostate cancer cells PC-3, demonstrating for the first time a meaningful electrical pattern. The low noise system used comprises a multi-electrode array (MEA) with circular gold electrodes on silicon oxide substrates. The extracellular capacitive currents present two standard patterns: an asynchronous sporadic pattern and a synchronous quasi-periodic biphasic spike pattern. An amplitude of &plusmn, 150 pA, a width between 50&ndash, 300 ms and an inter-spike interval around 0.5 Hz characterize the quasi-periodic spikes. Our experiments using treatment of cells with Gd3⁺, known as an inhibitor for the Ca2⁺ exchanges, suggest that the quasi-periodic signals originate from Ca2⁺ channels. After adding the Gd3⁺ to a population of living PC-3 cells, their electrical activity considerably decreased, once the culture was washed, thus eliminating the Gd3⁺ containing medium and addition of fresh cellular growth medium, the PC-3 cells recovered their normal electrical activity. Cellular viability plots have been carried out, demonstrating that the PC-3 cells remain viable after the use of Gd3⁺, on the timescale of this experiment. Hence, this experimental work suggests that Ca2⁺ is significantly affecting the electrophysiological communication pattern among PC-3 cell populations. Our measuring platform opens up new avenues for real time and highly sensitive investigations of prostate cancer signalling pathways.

The applications of coordination chemistry to molecular imaging has become a matter of intense research over the past 10 years. In particular, the applications of bis(thiosemicarbazonato) metal complexes in molecular imaging have mainly been focused on compounds with aliphatic backbones due to the in vivo imaging success of hypoxic tumors with PET (positron emission tomography) using 64CuATSM [copper (diacetyl-bis(N4-methylthiosemicarbazone))]. This compound entered clinical trials in the US and the UK during the first decade of the 21st century for imaging hypoxia in head and neck tumors. The replacement of the ligand backbone to aromatic groups, coupled with the exocyclic N's functionalization during the synthesis of bis(thiosemicarbazones) opens the possibility to use the corresponding metal complexes as multimodal imaging agents of use, both in vitro for optical detection, and in vivo when radiolabeled with several different metallic species. The greater kinetic stability of acenaphthenequinone bis(thiosemicarbazonato) metal complexes, with respect to that of the corresponding aliphatic ATSM complexes, allows the stabilization of a number of imaging probes, with special interest in “cold” and “hot” Cu(II) and Ga(III) derivatives for PET applications and 111In(III) derivatives for SPECT (single-photon emission computed tomography) applications, whilst Zn(II) derivatives display optical imaging properties in cells, with enhanced fluorescence emission and lifetime with respect to the free ligands. Preliminary studies have shown that gallium-based acenaphthenequinone bis(thiosemicarbazonato) complexes are also hypoxia selective in vitro, thus increasing the interest in them as new generation imaging agents for in vitro and in vivo applications.

We report the microwave synthesis of several bis(thiosemicarbazones) and the rapid gallium-68 incorporation to give the corresponding metal complexes. These proved kinetically stable under ‘cold’ and ‘hot’ biological assays and were investigated using laser scanning confocal microscopy, flow cytometry and radioactive cell retention studies under normoxia and hypoxia. 68Ga complex retention was found to be 34% higher in hypoxic cells than in normoxic cells over 30 min, further increasing to 53% at 120 min. Our data suggests that this class of gallium complexes show hypoxia selectivity suitable for imaging in living cells and in vivo tests by microPET in nude athymic mice showed that they are excreted within 1 h of their administration.

The application of rhenium complexes as therapeutic agents in nuclear medicine has propelled research into the chemistry of these compounds. In our effort to develop and investigate new therapeutic radiopharmaceuticals based on the complexes of rhenium we have investigated the nitride core, [ReN]2+. This work looks at the behavior of sulfonamide based dithiocarbimates towards the rhenium(V) nitride core. The aim here was to prepare anionic complexes with aromatic as well as fluorescent aromatic groups in the sulfonamide substituent located on the dithiocarbimate backbone. We envisaged that the polar sulfonamide and dianionic charge would confer solubility in water. Here we report the reactions of the dithiocarbimate ligands towards the rhenium(V) precursors: [ReNCl2(PPh3)2] and [ReNCl2(PMe2Ph)3]. These reactions proceeded with bis-substitution by the dithiocarbimate ligand, resulting in the formation of a dianionic rhenium(V) complex, of the type [ReN(S-S)2]2-, where (S-S) denotes the sulfonamide-tagged dithiocarbimato unit. Spectroscopic characterization data, as well as the synchrotron X-ray diffraction structure of the metal complex with the phenyl sulfonamide backbone shed light into the structural features of this interesting class of ligands and opens up opportunities for further studies in molecular imaging and therapeutic arenas.

This Tutorial Review aims to provide an overview of the use of zirconium-89 complexes in biomedical imaging. Over the past decade there have been many new papers in this field, ranging from chemistry through to preclinical and clinical applications. Here we attempt to summarise the main developments that have occurred in this period. The primary focus is on coordination chemistry but other aspects such as isotope production, isotope properties, handling and radiochemical techniques and characterisation of cold and labelled complexes are included. Selected results from animal and human clinical studies are presented in the context of the stabilities and properties of the labelled bioconjugates.

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

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.

A biocompatible fluoride receptor has been developed where the interaction between the boronic acid ester and amine (NH) results in fluoride ion selectivity and enhanced fluorescence quenching.

The synthesis of a new pyrene-containing Fischer carbene complex is described. The complex has a broad absorbance spectrum between 300 and 400 nm and, on excitation at 345 nm in CH2Cl2 solution, emission is observed at 395 and 415 nm. Emission is also observed in PBS buffer, but in this case the resulting spectra are much broader. Confocal and fluorescence lifetime imaging indicate that emission occurs on treating HeLa cells with the complex and co-localisation studies demonstrate that this is from the mitochondria and lipid-rich regions of the cell.

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).

Nanotechnology has potential to revolutionize diagnosis and therapy of diseases in the central nervous system through nanotheranostics. This simply states that a nanocarrier can be designed in an ‘all-in-one’ approach to facilitate both the functions of a diagnostic and a therapeutic drug. There are many challenges that must be overcome for these nanocarriers to become a successful design, but if resolved nanocarriers could pave the way for personalised medicine. This review highlights several new ideas behind nanotheranostics design and testing with a particular focus on cancerous tumours in the brain.

Copper ions are essential for many biological processes. However, high concentrations of copper can be detrimental to the cell or organism. A novel naphthalimide derivative bearing a monoboronic acid group (BNP) was investigated as a Cu2 selective fluorescent sensor in living cells. This derivative is one of the rare examples of reversible fluorescent chemosensors for Cu2 which uses a boronic acid group for a binding site. Moreover, the adduct BNP-Cu2 displays a fluorescence enhancement with fructose. The uptake of this novel compound in HeLa cancer cells was imaged using confocal fluorescence microscopy techniques including two-photon fluorescence lifetime imaging microscopy.

The direct conversion of carbon dioxide to hydrocarbons with a high economic value, such as olefins, can contribute to preventing further green house gas emissions in the atmosphere. In this paper, we report a synthesis, characterisation and catalytic study centred on iron nanoparticle-carbon nanotube arrays grown on monoliths (Fe@CNT-m). These have been used for the catalytic conversion of carbon dioxide to hydrocarbons, showing superior properties than the powder form. The monolith-supported structure also overcomes limitations of the powder catalyst, such as high-pressure drops and potential toxicity of airborne CNT powders, that have, so-far, limited its use in industry. The optimal process conditions (temperature pressure, flow rate and reaction time) have been identified along with deactivation mechanisms. The different catalytic performance of the residual iron NPs outside and inside the CNTs has also been investigated.

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.

In recent years, the use of metallic isotopes for nuclear imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) has become an area of much interest. In particular, PET is a molecular imaging modality that relies on the detection of two antiparallel, co-linear gamma rays (511 keV) emitted when a positron undergoes annihilation with an electron. PET isotopes of interest in medical practice are numerous and their use depends on their half-lives and introduction in the compounds of interest. These include: nitrogen-13 (t1/2 = 10 min), carbon-11 (t1/2 = 20 min), fluorine-18 (t1/2 = 110 min) and metallic isotopes such as gallium-68 (t1/2 = 68 min), titanium-45 (t1/2 = 3.08 h), copper-64 (t1/2 = 12.7 h), manganese-52 (t1/2 = 5.59 d) or zirconium-89 (t1/2 = 3.3 d). 89Zr has emerged as a promising isotope for radiotracer design and in vivo delivery, on basis of its ideal half-life matching the biological half-life of antibodies, antibody fragments and nanomedicines leading to high-resolution PET images for the pre-clinical and clinical investigations of a number of conditions including the prospective use in prostate cancers in the search of new diagnostic biomarkers. The availability of a plethora of chelators satisfying the coordination number of 8 such as siderophore-like chelators and recently nanoparticles conferring high kinetic and thermodynamic stabilities provides various designs and versatility in chemistry and radiochemistry. The aqueous chemistry of 89Zr is certainly of high importance for antibody-based imaging due to the match between the physical half- life of the nuclide and the biological half-life of the targeting vector, but mostly if there are no small molecules with more rapid pharmacokinetics available. This mini-review highlights some of the recently accounted advantages and disadvantages of current biomolecule-tagging techniques and proposes subtle radiotracer design changes that may be introduced in order to obtain a highly efficient targeted imaging with zirconium-labelled chemical entities and nanoconstructs. These may be of relevance to preclinical and clinical research towards the diagnosis of cancer in general, whilst highlighting some of the prostate cancer targeting approaches from the recent 89Zr-focused radiochemistry literature.

If CO2 hydrogenation is to become a viable process for the utilisation of CO2 , improved catalysts are urgently needed. We report the promotional effects of Group 11 and 13 metals on the performance of iron-silica catalyst systems under atmospheric pressure. The addition of low loadings of gold resulted in a significant improvement in catalyst performance both in terms of conversion and selectivity to lower (C2 -C4 ) olefins. Small loadings of indium proved highly effective for increasing CO2 conversion, whereas at higher loadings the selectivity to lower olefins could be dramatically increased. Catalysis tests involving palladium-promoted systems also proved successful with large increases in selectivity towards C5+ hydrocarbons observed. The catalysts were characterised by X-ray photoelectron spectroscopy, TEM and SEM, which confirmed the nanostructured nature of the catalytic species involved.

Low temperature carbonisation (500 °C) of poly-acrylonitrile nanofibres (typically 100 nm diameter) electrospun into a nanoweb-like deposit on tin-doped indium oxide (ITO) substrates (or as free-standing membrane over glass capillaries) yields active carbon film electrodes but with only relatively low electrochemical activity. Without resorting to higher carbonisation temperatures, substantial improvements in both electrical conductivity and electron transfer reactivity are observed after “surface-graphenisation”, that is coating with graphene-oxide prior to vacuum carbonisation. Improvements in voltammetric characteristics are demonstrated for both membranes mounted on ITO substrates and free-standing membranes suspended over the end of a borosilicate glass capillaries for (i) the aqueous phase hydroquinone/benzoquinone redox system and (ii) the biphasic oil|aqueous ion transfer redox system tetraphenylporphyrinato-Mn(III/II) in 4-phenyl-(3-propyl)-pyridine).

W(IV) and Nb(IV) derivatives: [W(L1)MeH] (1), [W(L1)MeH] (2) and [W(L1)O] (3), [W(L2)Cl-2](4), [W(L2)H-2](5), [W(L2)H-3][BF4] (6), [Nb(L2)Cl-2](7) and [Nb(L2)(eta(2)-BH4)](8), where L1 = [(eta-C5H4)(2)SiMe2](2-) and L2 = [(eta-C5H3TMS)(2)SiMe2](2-), have been prepared and characterised. The crystal structures of compounds 5 and 8 have been determined. Thermodynamic parameters for the elimination of methane from compound 2 have been evaluated based on H-1 NMR studies in C6D6. Trimethylsilyl substituents on the cyclopentadienyl rings appear to moderate the structural and dynamic properties of the silicon-bridged ansa-tungstenocenes. (c) 2005 Elsevier Ltd. All rights reserved.

A new iminophosphine ligand, [Ph2PCH2C(Ph)=N(2,6-Me2C6H 3)] (HL), and the complexes [PdX2(HL)], where X = Cl (1) and Br (2), [PdMeX(HL)], X = Cl (3) and Br (4), and [PdMe2(HL)] (5) have been prepared and characterised. Reaction of 2 with MeLi or KH leads to deprotonation of the neutral ligand to give [Pd2(μ-Br)2(L-)2], (6), where L- is [Ph2PCH=C(Ph)N(2,6-Me2C6H3)] -. Similarly, reaction of 3 with KH and triphenylphosphine affords the neutral complex [PdMe(PPh3(L-)] (7). Insertion of CO into the Pd-Me bond has been investigated, as well as the catalytic properties of [PdClMe(HL)] towards CO/ethylene copolymerisation. The crystal structures of HL, 1-3 and 5-7 have been determined.

Copper bis(4-ethyl-3-thiosemicarbazonato) acenaphthenequinone (1) and copper bis(4-methyl-3-thiosemicarbazonato) acenaphthenequinone (2) are synthesized and characterized in solution, in the solid state, and radiolabeled. Serum-protein binding radioassays show good stability in solution and about 25 % binding to protein over 1 h, which is comparable with the hypoxia selective tracer [(64)Cu(ATSM)]. Cyclic voltammetry shows fast and reversible reduction at redox potentials similar to the values known for hypoxia-selective copper compounds. However, despite this, complex 1 does not show any hypoxic-selective uptake in HeLa cells over 1-h standard assays. Possible reasons for this are studied by using the intrinsic fluorescence of the Cu(II) complexes to determine the cellular distributions and uptake mechanism by confocal microscopy. The complexes are found to bind to the external cell membrane and disperse evenly in the cytoplasm only after a very slow cell internalization (>1 h). No significant changes in distribution are observed by fluorescence imaging under hypoxic conditions. The rate of localization in the cytoplasm contrasts with their Zn(II) analogues, which are known to have fast cell uptake (up to 20 min) and a clear localization in lysosomes and mitochondria. The cytotoxicity mechanism of 1 over 24 h against a number of adherent cell lines is seen to be by membrane disruption and is of a comparable magnitude to that of [Cu(ATSM)], as demonstrated by methyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays.

Complexes of Cu(ii), Ni(ii) and Zn(ii) have been prepared with bis(thiosemicarbazonate) ligands bearing a pendant Bodipy fluorophore both with (ATSMBodipy) and without (GTSBodipy) backbone methyl groups. Biophysical analysis using steady state confocal laser scanning fluorescence images and excited state fluorescence lifetime imaging microscopy (FLIM) data obtained from live cells under aerobic uptake conditions has uniquely allowed both the spatial distribution and degree of dissociation of the complexes to be assessed. The CuATSMBodipy complex is virtually intact after 20 min and 1 h whereas the corresponding CuGTSBodipy complex is totally dissociated. The complexes ZnATSMBodipy and NiATSMBodipy show little evidence for dissociation. The relevance of this data to the biomedical applications of bis(thiosemicarbazonate) complexes for imaging applications and implications for the treatment of disease such as Alzheimer's and the PET imaging of hypoxia are discussed. This journal is © The Royal Society of Chemistry 2013.

Reactions between [Fe(η-C 5 H 5 )(MeCO)(CO)(L)], L = PPh 3 ( 1 ), PMe 3 ( 2 ), PPhMe 2 ( 3 ), PCy 3 ( 4 ), CO ( 5 ), and B(C 6 F 5 ) 3 give new complexes [Fe(η-C 5 H 5 ){MeCOB(C 6 F 5 ) 3 }(CO)(L)] L = PPh 3 ( 7 ), PMe 3 ( 8 ), PPhMe 2 ( 9 ), PCy 3 ( 10 ), CO ( 11 ), where B(C 6 F 5 ) 3 coordinates selectively to the O-acyl groups. Hydrolysis of 7 gives [Fe(η-C 5 H 5 ){HOB(C 6 F 5 ) 3 }(CO)(PPh 3 )] ( 6 ). The X-ray structures of 6 , 8 and 11 have been determined. Calculations, using density functional theory, demonstrate that the charge transfer to the acyl group on Lewis acid coordination is more significant in the σ than the π system. Both effects lead to a lengthening of the acyl C–O bond thus π populations cannot be inferred from the distance changes.

The design, synthesis, structure, and anion-binding properties of the first indolocarbazole-containing interlocked structure are described. The novel [2]rotaxane molecular structure incorporates a neutral indolocarbazole-containing axle component which is encircled by a tetracationic macrocycle functionalized with an isophthalamide anion recognition motif. (1)H NMR and UV-visible spectroscopies and X-ray crystallography demonstrated the importance of pi-donor-acceptor, CH...pi, and electrostatic interactions in the assembly of pseudorotaxanes between the electron-deficient tetracationic macrocycle and a series of pi-electron-rich indolocarbazole derivatives. Subsequent urethane stoppering of one of these complexes afforded a [2]rotaxane, which was shown by (1)H NMR spectroscopic titration experiments to exhibit enhanced chloride and bromide anion recognition compared to its non-interlocked components. Computational molecular dynamics simulations provide further insight into the mechanism and structural nature of the anion recognition process, confirming it to involve cooperative hydrogen-bond donation from both macrocycle and indolocarbazole components of the rotaxane. The observed selectivity of the [2]rotaxane for chloride is interpreted in terms of its unique interlocked binding cavity, defined by the macrocycle isophthalamide and indolocarbazole N-H protons, which is complementary in size and shape to this halide guest.

We describe a strategy for dispersing single walled nanotubes (SWNTs) in organic solvents using supramolecular coating with tailor-made, structurally adjustable tripodal porphyrin receptors. These have the ability to recognise SWNTs from DMF–toluene mixtures. HR TEM, TM AFM and SEM measurements showed that the hosts wrap around individual arc-made SWNTs, giving monodispersed composites in DMF which are stable for weeks. The dispersed composites were studied by Raman and fluorescence spectroscopies, including laser scanning confocal microscopy (for aggregates incorporated in cells). These porphyrin hosts encapsulate SWNTs based on π–π type interactions in an analogous manner to those observed by single crystal X-ray diffraction in their C60 complexes. These interactions may be further reinforced by porphyrin–porphyrin stacking. Density functional theory (DFT) calculations predicted the structure of the SWNT : porphyrin host complex or composite formed and the binding energies of tripodal porphyrin hosts in composites with either C60 or SWNT as guests.

The surface modification of graphene oxide (GO) is carried out via the supramolecular functionalization route using a Zn(II)-porphyrin which is soluble in common organic solvents on basis of long alkyl chains present at the exocyclic positions. This acts as a dispersing agent and decorates the surface of the graphene oxide uniformly, giving rise to a new nanohybrid denoted Zn(II)-porphyrin@GO. The resulting Zn(II)-porphyrin@GO nanohybrid forms a stable dispersion in ethanol (as characterized by several different spectroscopic techniques such as UVvis, Fourier transform infrared, Raman). The morphology of Zn(II)-porphyrin@GO nanohybrid is investigated by atomic force microscopy (AFM) and transmission electron microscope (TEM)/selected area electron diffraction. Both TEM and AFM measurements indicate that the Zn(II)-porphyrin self-assemble onto the surface of graphene oxide sheets. Steady-state and time-resolved fluorescence emission studies in the dispersed phase, and as a thin film, point toward the strongly quenched fluorescence emission and lifetime decay, suggesting that energy transfer occurs from the singlet excited state of Zn(II)-porphyrin unit to GO sheets., rof. Jeremy K. M. Sanders, FRS and the Sanders Group at Cambridge, as well as Prof. Sijbren Otto is acknowledged for training, helpful discussions in supramolecular chemistry and porphyrin synthesis and mentorship to SIP group. Dr. Amy Kieran, Dr. Lok Tong, and Dr. Rory Arrowsmith are thanked for involvement with initial stages of the porphyrin synthesis and characterization. S.I.P. and S.W.B. thank The Royal Society and STFC for funding. B.Y.M. thanks the University of Bath for a studentship (ORS). B.J.H. thanks the University of Bath for a DTC studentship. The SIP group thanks to the EPSRC for funding, as a member of the Centre of Graphene Science. The authors also acknowledge the ERC for the Consolidator Grant O2SENSE.