Photochemical Povarov-type Reactions: Electron Donor-Acceptor Photoactivation by Visible Light.

This report investigates the mechanism of photochemical Povarov-type reactions of N,N-dialkylanilines and maleimides in polar solvents (DMF or dioxane) in the presence of light. Fundamental aspects of the electron donor-acceptor (EDA) photoactivation pathway proposed to underpin this chemistry are examined through integrated experimental and computational studies. This approach provided evidence supporting the involvement of an EDA complex in facilitating this chemistry via a reaction mechanism that does not involve a triplet manifold. Most notably, our findings indicate that relying solely on UV-vis absorption spectroscopic data to either account for or predict reactivity in synthetic experiments may not always provide the complete picture. More specifically, this relates to considering UV-vis absorption spectroscopic data, calculated values for association constants (KEDA) and molar extinction coefficients (ε), with the reactivity observed in associated synthetic reactions in practice.

Electrochemiluminescence of a First-Row d6 Transition Metal Complex.

We report the electrochemiluminescence (ECL) of a 3d6 Cr(0) complex ([Cr(LMes)3]; λem=735 nm) with comparable photophysical properties to those of ECL-active complexes of 4d6 or 5d6 precious metal ions. The electrochemical potentials of [Cr(LMes)3] are more negative than those of [Ir(ppy)3] and render the [Cr(LMes)3]* excited state inaccessible through conventional co-reactant ECL with tri-n-propylamine or oxalate. ECL can be obtained, however, through the annihilation route in which potentials sufficient to oxidise and reduce the luminophore are alternately applied. When combined with [Ir(ppy)3] (λem=520 nm), the annihilation ECL of [Cr(LMes)3] was greatly enhanced whereas that of [Ir(ppy)3] was diminished. Under appropriate conditions, the relative intensities of the two spectrally distinct emissions can be controlled through the applied potentials. From this starting point for ECL with 3d6 metal complexes, we discuss some directions for future development.

Electrochemiluminescence Enhanced by a Non-Emissive Dual Redox Mediator.

A sulfonated tris(1-phenylpyrazolato)iridium(III) complex ([Ir(sppz)3]3-) serves as a proof-of-concept non-emissive enhancer of the widely used ECL detection system of tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy)3]2+) with tri-n-propylamine (TPrA) co-reactant, acting through electrocatalysis of TPrA oxidation and efficient chemi-excitation of the luminophore. Using self-interference ECL spectroscopy, we show that the enhancer extends diffusion of the required electrogenerated precursors from the electrode surface. Previously reported enhancement through these pathways has been confounded by the inherent ECL of the enhancer, but the increase in [Ru(bpy)3]2+ ECL intensity using [Ir(sppz)3]3- was obtained without its concomitant emission. The most prominent enhancement (11-fold) occurred at low potentials associated with the 'indirect' co-reactant ECL pathway, which translated to between 2- and 6-fold enhancement when the luminophore was immobilised on microbeads as a general model for enhanced ECL assays.

Extending Photocatalyst Activity through Choice of Electron Donor.

Sacrificial additives are commonly employed in photoredox catalysis as a convenient source of electrons, but what occurs after electron transfer is often overlooked. Tertiary alkylamines initially form radical cations following electron transfer, which readily deprotonate to form strongly reducing, neutral α-amino radicals. Similarly, the oxalate radical anion (C2O4•-) rapidly decomposes to form CO2•- (E0 ≈ -2.2 V vs SCE). We show that not only are these reactive intermediates formed under photoredox conditions, but they can also impact the desired photochemistry, both positively and negatively. Photoredox systems using oxalate as an electron donor are able to engage substrates with greater energy demands, extending reactivity past the energy limits of single and multiphoton transition metal catalysts. Furthermore, oxalate offers better chemoselectivity than the commonly employed triethylamine when reducing substrates with moderate energy requirements.

Photoinitiated Energy Transfer in Porous-Cage-Stabilised Silver Nanoparticles.

We report a new composite material consisting of silver nanoparticles decorated with three-dimensional molecular organic cages based on light-absorbing porphyrins. The porphyrin cages serve to both stabilize the particles and allow diffusion and trapping of small molecules close to the metallic surface. Combining these two photoactive components results in a Fano-resonant interaction between the porphyrin Soret band and the nanoparticle-localised surface-plasmon resonance. Time-resolved spectroscopy revealed the silver nanoparticles transfer up to 37 % of their excited-state energy to the stabilising layer of porphyrin cages. These unusual photophysics cause a 2-fold current increase in photoelectrochemical water-splitting measurements. The composite structure provides a compelling proof of concept for advanced photosensitiser systems with intrinsic porosity for photocatalytic and sensing applications.

Understanding Ir(III) Photocatalyst Structure-Activity Relationships: A Highly Parallelized Study of Light-Driven Metal Reduction Processes.

High-throughput synthesis and screening methods were used to measure the photochemical activity of 1440 distinct heteroleptic [Ir(C^N)2(N^N)]+ complexes for the photoreduction of Sn(II) and Zn(II) cations to their corresponding neutral metals. Kinetic data collection was carried out using home-built photoreactors and measured initial rates, obtained through an automated fitting algorithm, spanned between 0-120 µM/s for Sn(0) deposition and 0-90 µM/s for Zn(0) deposition. Photochemical reactivity was compared to photophysical properties previously measured such as deaerated excited state lifetime and emission spectral data for these same complexes; however, no clear correlations among these features were observed. A formal photochemical rate law was then developed to help elucidate the observed reactivity. Initial rates were found to be directly correlated to the product of incident photon flux with three reaction elementary efficiencies: (1) the fraction of light absorbed by the photocatalyst, (2) the fraction of excited state species that are quenched by the electron donor, and (3) the cage escape efficiency. The most active catalysts exhibit high efficiencies for all three steps, and catalyst engineering requirements to maximize these elementary efficiencies were postulated. The kinetic treatment provided the mechanistic information needed to decipher the observed structure/function trends in the high-throughput work.

Reinterpreting the Fate of Iridium(III) Photocatalysts─Screening a Combinatorial Library to Explore Light-Driven Side-Reactions.

Photoredox catalysts are primarily selected based on ground and excited state properties, but their activity is also intrinsically tied to the nature of their reduced (or oxidized) intermediates. Catalyst reactivity often necessitates an inherent instability, thus these intermediates represent a mechanistic turning point that affords either product formation or side-reactions. In this work, we explore the scope of a previously demonstrated side-reaction that partially saturates one pyridine ring of the ancillary ligand in heteroleptic iridium(III) complexes. Using high-throughput synthesis and screening under photochemical conditions, we identified different chemical pathways, ultimately governed by ligand composition. The ancillary ligand was the key factor that determined photochemical stability. Following photoinitiated electron transfer from a sacrificial tertiary amine, the reduced intermediate of complexes containing 1,10-phenanthroline derivatives exhibited long-term stability. In contrast, complexes containing 2,2'-bipyridines were highly susceptible to hydrogen atom transfer and ancillary ligand modification. Detailed characterization of selected complexes before and after transformation showed differing effects on the ground and excited state reduction potentials dependent on the nature of the cyclometalating ligands and excited states. The implications of catalyst stability and reactivity in chemical synthesis was demonstrated in a model photoredox reaction.

High-Throughput Screening and Automated Data-Driven Analysis of the Triplet Photophysical Properties of Structurally Diverse, Heteroleptic Iridium(III) Complexes.

Steady state emission spectra and excited state lifetimes were measured for 1440 distinct heteroleptic [Ir(C^N)2(N^N)]+ complexes prepared via combinatorial parallelized synthesis; 72% of the complexes were found to be luminescent, and the emission maxima of the library spanned the visible spectrum (652-459 nm). Spectral profiles ranged from broad structureless bands to narrow emissions exhibiting vibrational substructure. Measured excited state lifetimes ranged between ∼0.1-14 µs. Automated emission spectral fitting with successive Gaussian functions revealed four distinct measured classes of excited states; in addition to well understood metal-ligand to ligand-charge transfer (3MLLCT) and ligand-centered (3LC) excited states, our classification also identified photophysical characteristics of less explored mixed 3MLLCT/3LC states. Electronic structure features obtained from DFT calculations performed on a large subset of these Ir(III) chromophores offered clear insights into the excited state properties and allowed the prediction of structure/luminescence relationships in this class of commonly used photocatalysts. Models with high prediction accuracy (R2 = 0.89) for emission color were developed on the basis of experimental data. Furthermore, different degrees of nuclear reorganization in the excited state were shown to significantly impact emission energy and excited state lifetimes.

High-Throughput Screening of Earth-Abundant Water Reduction Catalysts toward Photocatalytic Hydrogen Evolution.

Noble-metal photosensitizers and water reduction co-catalysts (WRCs) still present the highest activity in homogeneous photocatalytic hydrogen production. The search for earth-abundant alternatives is usually limited by the time required to screen new catalyst combinations; however, here, we utilize newly designed and developed high-throughput photoreactors for the parallel synthesis of novel WRCs and colorimetric screening of hydrogen evolution. This unique approach allowed rapid optimization of photocatalytic water reduction using the organic photosensitizer Eosin Y and the archetypal cobaloxime WRC [Co(GL1)2pyCl], where GL1 is dimethylglyoxime and py is pyridine. Subsequent combinatorial synthesis generated 646 unique cobalt complexes of the type [Co(LL)2pyCl], where LL is a bidentate ligand, that identified promising new WRC candidates for hydrogen production. Density functional theory (DFT) calculations performed on such cobaloxime derivative complexes demonstrated that reactivity depends on hydride affinity. Alkyl-substituted glyoximes were necessary for hydrogen production and showed increased activity when paired with ligands containing strong hydrogen-bond donors.

Tandem Photoredox Catalysis: Enabling Carbonylative Amidation of Aryl and Alkylhalides.

We report a new visible-light-mediated carbonylative amidation of aryl, heteroaryl, and alkyl halides. A tandem catalytic cycle of [Ir(ppy)2 (dtb-bpy)]+ generates a potent iridium photoreductant through a second catalytic cycle in the presence of DIPEA, which productively engages aryl bromides, iodides, and even chlorides as well as primary, secondary, and tertiary alkyl iodides. The versatile in situ generated catalyst is compatible with aliphatic and aromatic amines, shows high functional-group tolerance, and enables the late-stage amidation of complex natural products.

The Tandem Photoredox Catalysis Mechanism of [Ir(ppy)2(dtb-bpy)]+ Enabling Access to Energy Demanding Organic Substrates.

We report the discovery of a tandem catalytic process to reduce energy demanding substrates, using the [Ir(ppy)2(dtb-bpy)]+ (1+) photocatalyst. The immediate products of photoinitiated electron transfer (PET) between 1+ and triethylamine (TEA) undergo subsequent reactions to generate a previously unknown, highly reducing species (2). Formation of 2 occurs via reduction and semisaturation of the ancillary dtb-bpy ligand, where the TEA radical cation serves as an effective hydrogen atom donor, confirmed by nuclear magnetic resonance, mass spectrometry, and deuterium labeling experiments. Steady-state and time-resolved luminescence and absorption studies reveal that upon irradiation, 2 undergoes electron transfer or proton-coupled electron transfer (PCET) with a representative acceptor (N-(diphenylmethylene)-1-phenylmethanamine; S). Turnover of this new photocatalytic cycle occurs along with the reformation of 1+. We rationalize our observations by proposing the first example of a mechanistic pathway where two distinct yet interconnected photoredox cycles provide access to an extended reduction potential window capable of engaging a wide range of energy demanding and synthetically relevant organic substrates including aryl halides.

Mixed annihilation electrogenerated chemiluminescence of iridium(iii) complexes.

Previously reported annihilation ECL of mixtures of metal complexes have generally comprised Ir(ppy)3 or a close analogue as a higher energy donor/emitter (green/blue light) and [Ru(bpy)3]2+ or its derivative as a lower energy acceptor/emitter (red light). In contrast, here we examine Ir(ppy)3 as the lower energy acceptor/emitter, by combining it with a second Ir(iii) complex: [Ir(df-ppy)2(ptb)]+ (where ptb = 1-benzyl-1,2,3-triazol-4-ylpyridine). The application of potentials sufficient to attain the first single-electron oxidation and reduction products can be exploited to detect Ir(ppy)3 at orders of magnitude lower concentration, or enhance its maximum emission intensity at high concentration far beyond that achievable through conventional annihilation ECL of Ir(ppy)3 involving comproportionation. Moreover, under certain conditions, the colour of the emission can be selected through the applied electrochemical potentials. We have also prepared a novel Ir(iii) complex with a sufficiently low reduction potential that the reaction between its reduced form and Ir(ppy)3+ cannot populate the excited state of either luminophore. This enabled, for the first time, the exclusive formation of either excited state through the application of higher cathodic or anodic potentials, but in both cases, the ECL was greatly diminished by parasitic dark reactions.

Luminescence of a Transition Metal Complex Inside a Metamaterial Nanocavity.

Modification of the local density of optical states using metallic nanostructures leads to enhancement in the number of emitted quanta and photocatalytic turnover of luminescent materials. In this work, the fabrication of a metamaterial is presented that consists of a nanowire separated from a metallic mirror by a polymer thin film doped with a luminescent organometallic iridium(III) complex. The large spin-orbit coupling of the heavy metal atom results in an excited state with significant magnetic-dipole character. The nanostructured architecture supports two distinct optical modes and their assignment achieved with the assistance of numerical simulations. The simulations show that one mode is characterized by strong confinement of the electric field and the other by strong confinement of the magnetic field. These modes elicit drastic changes in the emitter's photophysical properties, including dominant nanocavity-derived modes observable in the emission spectra along with significant increases in emission intensity and the total decay rate. A combination of simulations and momentum-resolved spectroscopy helps explain the mechanism of the different interactions of each optical mode supported by the metamaterial with the excited state of the emitter.

Analytically useful blue chemiluminescence from a water-soluble iridium(III) complex containing a tetraethylene glycol functionalised triazolylpyridine ligand.

We examine [Ir(df-ppy)2(pt-TEG)](+) as the first highly water soluble, blue-luminescent iridium(III) complex for chemiluminescence detection. Marked differences in selectivity were observed between the new complex and the conventional [Ru(bpy)3](2+) reagent, which will enable this mode of detection to be extended to new areas of application.

Luminescent Iridium(III) Cyclometalated Complexes with 1,2,3-Triazole "Click" Ligands.

A series of cyclometalated iridium(III) complexes with either 4-(2-pyridyl)-1,2,3-triazole or 1-(2-picolyl)-1,2,3-triazole ancillary ligands to give complexes with either 5- or 6-membered chelate rings were synthesized and characterized by a combination of X-ray crystallography, electron spin ionization-high-resolution mass spectroscopy (ESI-HRMS), and nuclear magnetic resonance (NMR) spectroscopy. The electronic properties of the complexes were probed using absorption and emission spectroscopy, as well as cyclic voltammetry. The relative stability of the complexes formed from each ligand class was measured, and their excited-state properties were compared. The emissive properties are, with the exception of complexes that contain a nitroaromatic substituent, insensitive to functionalization of the ancillary pyridyl-1,2,3-triazole ligand but tuning of the emission maxima was possible by modification of the cyclometalating ligands. It is possible to prepare a wide range of optimally substituted pyridyl-1,2,3-triazoles using copper Cu(I)-catalyzed azide alkyne cycloaddition, which is a commonly used "click" reaction, and this family of ligands represent an useful alternative to bipyridine ligands for the preparation of luminescent iridium(III) complexes.

Protein Labelling with Versatile Phosphorescent Metal Complexes for Live Cell Luminescence Imaging.

To take advantage of the luminescent properties of d(6) transition metal complexes to label proteins, versatile bifunctional ligands were prepared. Ligands that contain a 1,2,3-triazole heterocycle were synthesised using Cu(I) catalysed azide-alkyne cycloaddition "click" chemistry and were used to form phosphorescent Ir(III) and Ru(II) complexes. Their emission properties were readily tuned, by changing either the metal ion or the co-ligands. The complexes were tethered to the metalloprotein transferrin using several conjugation strategies. The Ir(III)/Ru(II)-protein conjugates could be visualised in cancer cells using live cell imaging for extended periods without significant photobleaching. These versatile phosphorescent protein-labelling agents could be widely applied to other proteins and biomolecules and are useful alternatives to conventional organic fluorophores for several applications.

Blue Electrogenerated Chemiluminescence from Water-Soluble Iridium Complexes Containing Sulfonated Phenylpyridine or Tetraethylene Glycol Derivatized Triazolylpyridine Ligands.

Incorporating phenylpyridine- and triazolylpyridine-based ligands decorated with methylsulfonate or tetraethylene glycol (TEG) groups, a series of iridium(III) complexes has been created for green and blue electrogenerated chemiluminescence under analytically useful aqueous conditions, with tri-n-propylamine as a coreactant. The relative electrochemiluminescence (ECL) intensities of the complexes were dependent on the sensitivity of the photodetector over the wavelength range and the pulse time of the applied electrochemical potential. In terms of the integrated area of corrected ECL spectra, with a pulse time of 0.5 s, the intensities of the Ir(III) complexes were between 18 and 102 % that of [Ru(bpy)3 ](2+) (bpy=2,2'-bipyridine). However, when the intensities were measured with a typical bialkali photomultiplier tube, the signal of the most effective blue emitter, [Ir(df-ppy)2 (pt-TEG)](+) (df-ppy=2-(2,4-difluorophenyl)pyridine anion, pt-TEG=1-(2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)ethyl)-4-(2-pyridyl)-1,2,3-triazole), was over 1200 % that of the orange-red emitter [Ru(bpy)3 ](2+) . A combined experimental and theoretical investigation of the electrochemical and spectroscopic properties of the Ir(III) complexes indicated that the greater intensity from [Ir(df-ppy)2 (pt-TEG)](+) relative to those of the other Ir(III) complexes resulted from a combination of many factors, rather than being significantly favored in one area.

A versatile approach for the site-specific modification of recombinant antibodies using a combination of enzyme-mediated bioconjugation and click chemistry.

A unique two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for incorporation of strained cyclooctyne functional groups. The second step of this modular approach involves the azide-alkyne cycloaddition click reaction. The versatility of the two-step approach has been exemplified by the selective incorporation of fluorescent dyes and a positron-emitting copper-64 radiotracer for fluorescence and positron-emission tomography imaging of activated platelets, platelet aggregates, and thrombi, respectively. This flexible and versatile approach could be readily adapted to incorporate a large array of tailor-made functional groups using reliable click chemistry whilst preserving the activity of the antibody or other sensitive biological macromolecules.

Understanding electrogenerated chemiluminescence efficiency in blue-shifted iridium(III)-complexes: an experimental and theoretical study.

Compared to tris(2-phenylpyridine)iridium(III) ([Ir(ppy)3 ]), iridium(III) complexes containing difluorophenylpyridine (df-ppy) and/or an ancillary triazolylpyridine ligand [3-phenyl-1,2,4-triazol-5-ylpyridinato (ptp) or 1-benzyl-1,2,3-triazol-4-ylpyridine (ptb)] exhibit considerable hypsochromic shifts (ca. 25-60 nm), due to the significant stabilising effect of these ligands on the HOMO energy, whilst having relatively little effect on the LUMO. Despite their lower photoluminescence quantum yields compared with [Ir(ppy)3 ] and [Ir(df-ppy)3 ], the iridium(III) complexes containing triazolylpyridine ligands gave greater electrogenerated chemiluminescence (ECL) intensities (using tri-n-propylamine (TPA) as a co-reactant), which can in part be ascribed to the more energetically favourable reactions of the oxidised complex (M(+) ) with both TPA and its neutral radical oxidation product. The calculated iridium(III) complex LUMO energies were shown to be a good predictor of the corresponding M(+) LUMO energies, and both HOMO and LUMO levels are related to ECL efficiency. The theoretical and experimental data together show that the best strategy for the design of efficient new blue-shifted electrochemiluminophores is to aim to stabilise the HOMO, while only moderately stabilising the LUMO, thereby increasing the energy gap but ensuring favourable thermodynamics and kinetics for the ECL reaction. Of the iridium(III) complexes examined, [Ir(df-ppy)2 (ptb)](+) was most attractive as a blue-emitter for ECL detection, featuring a large hypsochromic shift (λmax =454 and 484 nm), superior co-reactant ECL intensity than the archetypal homoleptic green and blue emitters: [Ir(ppy)3 ] and [Ir(df-ppy)3 ] (by over 16-fold and threefold, respectively), and greater solubility in polar solvents.

Copper and silver complexes of tris(triazole)amine and tris(benzimidazole)amine ligands: evidence that catalysis of an azide-alkyne cycloaddition ("click") reaction by a silver tris(triazole)amine complex arises from copper impurities.

The synthesis and characterization of a silver complex of the tripodal triazole ligand, tris(benzyltriazolylmethyl)amine (TBTA, L(1)), that is used as promoter to enhance Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions is reported. X-ray analysis of the silver(I) complex with L(1) reveals a dinuclear cation, [Ag2(L(1))2](2+), that is essentially isostructural to the copper(I) analogue. While the [Ag2(L(1))2](BF4)2 complex provides catalysis for the azide-alkyne cycloaddition process, evidence is presented that this arises from trace copper contamination. The synthesis of silver(I), copper(II), and copper(I) complexes of a second tripodal ligand, tris(2-benzimidazolymethyl)amine (L(2)), which is used to enhance the rate of CuAAC reactions, is also reported. X-ray crystallography of the Cu(I) complex [Cu(I)3(L(2))2(CH3CN)2](BF4)3 offers structural insight into previous mechanistic speculation about the role of this ligand in the CuAAC reaction.