Synthesis, X-ray Structures, and Optical and Magnetic Properties of Cu(II) Octafluoro-octakisperfluoro(isopropyl)phthalocyanine: The Effects of Electron Addition and Fluorine Accretion.

The stepwise reduction of copper(II) 1,4,8,11,15,18,22,25-octafluoro-2,3,9,10,16,17,23,24-octakisperfluoro(isopropyl) phthalocyanine (CuIIF64Pc) in o-dichlorobenzene (C6H4Cl2) by potassium graphite in the presence of cryptand(K+), abbreviated L+, results in the formation of (L+)[CuII(F64Pc•3-)]-·2C6H4Cl2 (1), (L+)2[CuII(F64Pc4-)]2-·C6H4Cl2 (2), and (L+)2[CuII(F64Pc4-)]2- (3) complexes. Single-crystal X-ray structures revealed their composition and a monotonic increase with increased phthalocyanine (Pc) negative charges of the magnitude of alternative shortening and elongation of the prior equivalent Nmeso-C bonds. The complexes are separated by bulky i-C3F7 substituents, large cryptand counterions, and solvent molecules. Weak, new bands are generated in the visible and near-infrared (NIR) domains upon reductions. The one-electron reduced complex, [CuII(F64Pc•3-)]-, is a diradical, exhibiting broad electron paramagnetic resonance (EPR) signals, with intermediate parameters between those typical to CuII and F64Pc•3-. The two-electron reduced complexes, [CuII(F64Pc4-)]2-, contain a diamagnetic F64Pc4- macrocycle and a single spin, S = 1/2, on CuII. The bulky perfluoroisopropyl groups are suppressing intermolecular π-π interactions between Pcs in the [CuII(F64Pcn-)](n-2)- (n = 3, 4) anions, 1-3, similar to the case of the nonreduced complex. However, π-π interactions between 1 and o-dichlorobenzene are observed. The d9 and Pc electrons in 1 are antiferromagnetically coupled, J = -0.56 cm-1, as revealed by superconducting quantum interference device (SQUID) magnetometry, but the coupling is at least 1 order of magnitude smaller compared with the coupling observed for CuII(F8Pc•3-) and CuII(F16Pc•3-), a testimony to the F accretion effect of rendering the Pc macrocycle progressively more electron-deficient. The data for CuII(F64Pc) provide structural, spectroscopic, and magnetochemical insights, which establish a trend of the effects of fluorine and charge variations of fluorinated Pcs within the macrocycle series CuII(FxPc), x = 8, 16, 64. Diamagnetic Pcs might be useful for photodynamic therapy (PDT) and related biomedical applications, while the solvent-processable biradicalic nature of the monoanion salts may constitute the basis for designing robust, air-stable electronic, and magnetically condensed materials.

Photoelectrochemical Behavior of Phthalocyanine-Sensitized TiO2 in the Presence of Electron-Shuttling Mediators.

Dye-sensitized TiO2 has found many applications for dye-sensitized solar cells (DSSC), solar-to-chemical energy conversion, water/air purification systems, and (electro)chemical sensors. We report an electrochemical system for testing dye-sensitized materials that can be utilized in photoelectrochemical (PEC) sensors and energy conversion. Unlike related systems, the reported system does not require a direct electron transfer from semiconductors to electrodes. Rather, it relies on electron shuttling by redox mediators. A range of model photocatalytic materials were prepared using three different TiO2 materials (P25, P90, and PC500) and three sterically hindered phthalocyanines (Pcs) with electron-rich tert-butyl substituents (t-Bu4PcZn, t-Bu4PcAlCl, and t-Bu4PcH2). The materials were compared with previously developed TiO2 modified by electron-deficient, also sterically hindered fluorinated phthalocyanine F64PcZn, a singlet oxygen (1O2) producer, as well as its metal-free derivative, F64PcH2. The PEC activity depended on the redox mediator, as well as the type of TiO2 and Pc. By comparing the responses of one-electron shuttles, such as K4Fe(CN)4, and 1O2-reactive electron shuttles, such as phenol, it is possible to reveal the action mechanism of the supported photosensitizers, while the overall activity can be assessed using hydroquinone. t-Bu4PcAlCl showed significantly lower blank responses and higher specific responses toward chlorophenols compared to t-Bu4PcZn due to the electron-withdrawing effect of the Al3+ metal center. The combination of reactivity insights and the need for only microgram amounts of sensing materials renders the reported system advantageous for practical applications.

Correlation between the Fluorination Degree of Perfluorinated Zinc Phthalocyanines, Their Singlet Oxygen Generation Ability, and Their Photoelectrochemical Response for Phenol Sensing.

Electron-withdrawing perfluoroalkyl peripheral groups grafted on phthalocyanine (Pc) macrocycles improve their single-site isolation, solubility, and resistance to self-oxidation, all beneficial features for catalytic applications. A high degree of fluorination also enhances the reducibility of Pcs and could alter their singlet oxygen (1O2) photoproduction. The ethanol/toluene 20:80 vol % solvent mixture was found to dissolve perfluorinated FnPcZn complexes, n = 16, 52, and 64, and minimize the aggregation of the sterically unencumbered F16PcZn. The 1O2 production ability of FnPcZn complexes was examined using 9,10-dimethylanthracene (DMA) and 2,2,6,6-tetramethylpiperidine (TEMP) in combination with UV-vis and electron paramagnetic resonance (EPR) spectroscopy, respectively. While the photoreduction of F52PcZn and F64PcZn in the presence of redox-active TEMP lowered 1O2 production, DMA was a suitable 1O2 trap for ranking the complexes. The solution reactivity was complemented by solid-state studies via the construction of photoelectrochemical sensors based on TiO2-supported FnPcZn, FnPcZn|TiO2. Phenol photo-oxidation by 1O2, followed by its electrochemical reduction, defines a redox cycle, the 1O2 production having been found to depend on the value of n and structural features of the supported complexes. Consistent with solution studies, F52PcZn was found to be the most efficient 1O2 generator. The insights on reactivity testing and structural-activity relationships obtained may be useful for designing efficient and robust sensors and for other 1O2-related applications of FnPcZn.

Nanobody-Based Immunosensor Detection Enhanced by Photocatalytic-Electrochemical Redox Cycling.

Detection of antigenic biomarkers present in trace amounts is of crucial importance for medical diagnosis. A parasitic disease, human toxocariasis, lacks an adequate diagnostic method despite its worldwide occurrence. The currently used serology tests may stay positive even years after a possibly unnoticed infection, whereas the direct detection of a re-infection or a still active infection remains a diagnostic challenge due to the low concentration of circulating parasitic antigens. We report a time-efficient sandwich immunosensor using small recombinant single-domain antibodies (nanobodies) derived from camelid heavy-chain antibodies specific to Toxocara canis antigens. An enhanced sensitivity to pg/mL levels is achieved by using a redox cycle consisting of a photocatalytic oxidation and electrochemical reduction steps. The photocatalytic oxidation is achieved by a photosensitizer generating singlet oxygen (1O2) that, in turn, readily reacts with p-nitrophenol enzymatically produced under alkaline conditions. The photooxidation produces benzoquinone that is electrochemically reduced to hydroquinone, generating an amperometric response. The light-driven process could be easily separated from the background, thus making amperometric detection more reliable. The proposed method for detection of the toxocariasis antigen marker shows superior performances compared to other detection schemes with the same nanobodies and outperforms by at least two orders of magnitude the assays based on regular antibodies, thus suggesting new opportunities for electrochemical immunoassays of challenging low levels of antigens.

Enhanced Photoelectrochemical Detection of an Analyte Triggered by Its Concentration by a Singlet Oxygen-Generating Fluoro Photosensitizer.

The use of a photocatalyst (photosensitizer) which produces singlet oxygen instead of enzymes for oxidizing analytes creates opportunities for designing cost-efficient and sensitive photoelectrochemical sensors. We report that perfluoroisopropyl-substituted zinc phthalocyanine (F64PcZn) interacts specifically with a complex phenolic compound, the antibiotic rifampicin (RIF), but not with hydroquinone or another complex phenolic compound, the antibiotic doxycycline. The specificity is imparted by the selective preconcentration of RIF in the photocatalytic layer, as revealed by electrochemical and optical measurements, complemented by molecular modeling that confirms the important role of a hydrophobic cavity formed by the iso-perfluoropropyl groups of the photocatalyst. The preconcentration effect favorably enhances the RIF photoelectrochemical detection limit as well as sensitivity to nanomolar (ppb) concentrations, LOD = 7 nM (6 ppb) and 2.8 A·M-1·cm-2, respectively. The selectivity to RIF, retained in the photosensitizer layer, is further enhanced by the selective removal of all unretained phenols via simple washing of the electrodes with pure buffer. The utility of the sensor for analyzing municipal wastewater was demonstrated. This first demonstration of enhanced selectivity and sensitivity due to intrinsic interactions of a molecular photocatalyst (photosensitizer) with an analyte, without use of a biorecognition element, may allow the design of related, robust, simple, and viable sensors.

The influence of intermolecular coupling on electron and ion transport in differently substituted phthalocyanine thin films as electrochromic materials: a chemistry application of the Goldilocks principle.

The transport of both electrons and ions in organic mixed ionic and electronic conductors such as phthalocyanines, is essential to allow redox reactions of entire films and, hence, to impart electrochromism. Thin films of a new type, tetrakis-perfluoroisopropyl-perfluoro phthalocyanine, F40PcCu of different thicknesses were obtained via vapor deposition. The extent of the intermolecular coupling within the F40PcCu films established by van der Waals interactions was investigated by in situ optical spectroscopy during film growth. The transfer of electrons and diffusion of counter cations in these films, as well as their electrochromic performance were characterized by electrochemical and spectroelectrochemical measurements with an aqueous solution of KCl as electrolyte. A moderate degree of intermolecular interaction of the F40PcCu molecules in the solid state was observed, compared to non-fluoroalkylated perfluoro phthalocyanine, F16PcCu and octakis-perfluoroisopropyl-perfluorophthalocyanine, F64PcCu, which exhibit stronger and weaker coupling, respectively. The replacement of F by perfluoroisopropyl is, thereby, established as a valuable approach to tune this coupling of chromophores and, hence, the transport coefficients of electrons and ions in the solid films. Reversible changes of the films upon reduction and intercalation of K+ counter ions and re-oxidation and expulsion of the counter ions were confirmed by simultaneously measured optical absorption spectra. Thin films of F40PcCu showed a well-balanced, equally fast transport of electrons and ions. The films provided a fast and reversible switching process over at least 200 cycles indicating the stability of these materials.

Optimized Photoelectrochemical Detection of Essential Drugs Bearing Phenolic Groups.

The World Health Organization (WHO) model "List of Essential Medicines" includes among indispensable medicines antibacterials and pain and migraine relievers. Monitoring their concentration in the environment, while challenging, is important in the context of antibiotic resistance as well as their production of highly toxic compounds via hydrolysis. Traditional detection methods such as high-performance liquid chromatography (HPLC) or LC combined with tandem mass spectrometry or UV-vis spectroscopy are time-consuming, have a high cost, require skilled operators and are difficult to adapt for field operations. In contrast, (electrochemical) sensors have elicited interest because of their rapid response, high selectivity, and sensitivity as well as potential for on-site detection. Previously, we reported a novel sensor system based on a type II photosensitizer, which combines the advantages of enzymatic sensors (high sensitivity) and photoelectrochemical sensors (easy baseline subtraction). Under red-light illumination, the photosensitizer produces singlet oxygen which oxidizes phenolic compounds present in the sample. The subsequent reduction of the oxidized phenolic compounds at the electrode surface gives rise to a quantifiable photocurrent and leads to the generation of a redox cycle. Herein we report the optimization in terms of pH and applied potential of the photoelectrochemical detection of the hydrolysis product of paracetamol, i.e., 4-aminophenol (4-AP), and two antibacterials, namely, cefadroxil (CFD, ß-lactam antibiotic) and doxycycline (DXC, tetracycline antibiotic). The optimized conditions resulted in a detection limit of 0.2 µmol L-1 for DXC, but in a 10 times higher sensitivity, 20 nmol L-1, for CFD. An even higher sensitivity, 7 nmol L-1, was noted for 4-AP.

Synthesis and Photophysical and Photocatalytic Properties of a Highly Fluorinated and Durable Phthalocyanine-Peptide Bioconjugate for Potential Theranostic Applications.

The functionalized, asymmetric fluoro-fluoroalkyl scaffold F48H7COOHPcZn (3) was used to prepare F48H7COOPcZn-6-amino-hexanoate-CTVALPGGYVRVC (5), a Pep42 peptide bioconjugate envisioned for photodynamic therapy, which can specifically target the GRP78 chaperone protein overexpressed and exclusively localized on some cancer cell surfaces. The analogous F48H7COOHPcCu (4) has also been prepared, and its single-crystal X-ray structure was elucidated. Despite reduced steric hindrance relative to the nonfunctionalized, single-site complexes of the F64Pc scaffold, no aggregation was detected in solution via UV-vis spectroscopy, for either 3, 4, or 5, consistent with the lack of π stacking observed for the crystalline 4. The 6-aminohexanoic acid-Pep42 moiety diminishes the fluorescence efficiency of 5, relative to 3, but for singlet oxygen (1O2) generation, photochemical hydroperoxidation of ß-(-)-citronellol using 5 and 3 occurs with comparable substrate turnover efficiency, albeit at a slower initial triplet oxygen uptake for 5. The bioconjugate 5 is durable; it does not decompose under 1O2 photoreaction conditions. These results suggest a synthetic coupling pathway for obtaining diverse biotargeting polypeptide-fluorinated phthalocyanine bioconjugates of potential utility as both fluorescence reporters and photocatalysts and highlight the importance of fluorinated scaffolds for generating chemically resilient, catalytic, theranostic materials.

Photoreduction and light-induced triplet-state formation in a single-site fluoroalkylated zinc phthalocyanine.

Electron-withdrawing perfluoroalkyl peripheral substituents enhance the photosensitizing properties of metal phthalocyanines while increasing their solubility, thus providing opportunities for advanced characterization of their catalytically-relevant excited states. Optical absorption and electron paramagnetic resonance (EPR) spectroscopy experiments reveal that red light induces the reduction of perfluoroisopropyl-substituted zinc(ii) phthalocyanine (F64PcZn) dissolved in ethanol. A similar photoreduction does not occur in toluene. Furthermore, intense UV irradiation causes the photodegradation of F64PcZn in ethanol, but low power UV illumination favours the formation of the triplet excited state, a prerequisite for new photocatalytic applications. The UV-induced triplet state of F64PcZn is characterized using a combination of transient EPR experiments and DFT computations.

An improved synthesis of 3,6-anhydro-D-glucal and a study of its unusual chemical reactivity.

6-O-Tosyl-d-glucal 1 upon treatment with excess LiAlH4 unexpectedly gave 3,6-anhydro-d-glucal 2 as a major product in good yield. A crystal structure was obtained. Reaction of the anhydride 2 with N-iodosuccinimide (NIS) in excess methanol resulted in the formation of diastereomeric 2-deoxy-2-iodoglycosides. Addition of ceric (IV) ammonium nitrate and thiophenol to a solution of 2 in acetonitrile gave a mixture of 2-deoxy and 2,3-unsaturated thioglycosides. Reaction of 1,2:3,4-di-O-isopropylidine-α-d-galactopyranose with the anhydro sugar 2 in the presence of N-iodosuccinimide did not give the expected iodoglycoside mixture, but instead gave an unusual 1,4:3,6-dianhydride 7 as the major product.

Chemically robust fluoroalkyl phthalocyanine-oligonucleotide bioconjugates and their GRP78 oncogene photocleavage activity.

The first representative of functionalized fluoroalkyl phthalocyanines, F48H7(COOH)PcZn, is reported. The complex generates (1)O2 affording long-lasting photooxidation of an external substrate without self-decomposition. The carboxylic group couples with an antisense oligonucleotide targeting GRP78 oncogenes, resulting in the F48H7PcZn-cancer targeting oligonucleotide (CTO). The bioconjugated fluorophthalocyanine effectively hybridizes complementary GRP78 DNA and mRNA sequences. Piperidine cleavage assays reveal desired photochemical oligonucleotide oxidative degradation for both F48H7PcZn-CTO:DNA and F48H7PcZn-CTO:mRNA hybrids. This new materials strategy could be extended to other functional fluorinated phthalocyanines-antisense oligonucleotide combinations for long-lasting oncogene-targeting photodynamic therapy.

Highly reduced double-decker single-molecule magnets exhibiting slow magnetic relaxation.

F64Pc2Ln (1Ln, Ln = Tb or Lu) represent the first halogenated phthalocyanine double-decker lanthanide complexes, and 1Tb exhibits single-molecule magnet properties as revealed by solid-state magnetometry. The fluorine substituents of the phthalocyanine rings have a dramatic effect on the redox properties of the F64Pc2Ln complexes, namely, a stabilization of their reduced states. Electrochemical and spectroelectrochemical measurements demonstrate that the 1Tb(-/2-) and 1Tb(2-/3-) couples exhibit redox reversibility and that the 1Tb(-), 1Tb(2-) and 1Tb(3-) species may be prepared by bulk electrolysis in acetone. Low-temperature MCD studies reveal for the first time magnetization hystereses for the super-reduced dianionic and trianionic states of Pc2Ln.

Time-resolved singlet oxygen luminescence detection under photodynamic therapy relevant conditions: comparison of ex vivo application of two photosensitizer formulations.

Singlet oxygen plays a crucial role in photo-dermatology and photodynamic therapy (PDT) of cancer. Its direct observation by measuring the phosphorescence at 1270 nm, however, is still challenging due to the very low emission probability. It is especially challenging for the time-resolved detection of singlet oxygen kinetics in vivo which is of special interest for biomedical applications. Photosensitized generation of singlet oxygen, in pig ear skin as model for human skin, is investigated here. Two photosensitizers (PS) were topically applied to the pig ear skin and examined in a comparative study, which include the amphiphilic pheophorbide-a and the highly hydrophobic perfluoroalkylated zinc phthalocyanine (F64PcZn). Fluorescence microscopy indicates the exclusive accumulation of pheophorbide-a in the stratum corneum, while F64PcZn can also accumulate in deeper layers of the epidermis of the pig ear skin. The kinetics obtained with phosphorescence measurements show the singlet oxygen interaction with the PS microenvironment. Different generation sites of singlet oxygen correlate with the luminescence kinetics. The results show that singlet oxygen luminescence detection can be used as a diagnostic tool, not only for research, but also during treatment. The detection methodology is suitable for the monitoring of chemical quenchers' oxidation as well as saturation at singlet oxygen concentration levels relevant to PDT treatment protocols.

Structures and redox characteristics of electron-deficient vanadyl phthalocyanines.

The first single-crystal X-ray structures of substituted vanadyl phthalocyanine materials reveal the high-valence vanadium ions (denoted as V(IV)), whose coordination by a highly electron-deficient ligand is facilitated by an axial oxo group. The metal center of the hydrophilic V═O core, encapsulated in F-rich hydrophobic pockets, reaches a coordination number of 6 by binding an additional H(2)O that, in turn, hydrogen-bonds with ketones, resulting in solvent-induced variable solid-state architectures. Fluoroalkyl (R(f)) ligand substituents hinder π-π stacking interactions and favor ordered long-range packing, as well as the facile formation of film materials that exhibit high thermal stability and oxidation resistance. Reversible redox chemistry and spectroscopic studies in both solution and the solid-state indicate single-site isolation in both phases and an R(f)-induced propensity for electron uptake and inhibition of electron loss. Repeated redox cycles reorganize the thin films to accommodate Li(+) ions and facilitate their migration. The facile reduction, combined with high stability and ease of sublimation imparted by the R(f) scaffold that suppresses oxidations, recommends the new materials for sensors, color displays, electronic materials, and redox catalysts, as well as other applications.

Broadening the reactivity spectrum of a phthalocyanine catalyst while suppressing its nucleophilic, electrophilic and radical degradation pathways.

A robust molecule that resists degradation via nucleophilic, electrophilic and radical attacks is described. Coordinated O(2) is reduced catalytically, producing efficiently thyil radicals in spite of the extreme electronic deficiency of the catalyst.

Synthesis, X-ray structure, magnetic resonance, and DFT analysis of a soluble copper(II) phthalocyanine lacking C-H bonds.

The synthesis, crystal structure, and electronic properties of perfluoro-isopropyl-substituted perfluorophthalocyanine bearing a copper atom in the central cavity (F(64)PcCu) are reported. While most halogenated phthalocyanines do not exhibit long-term order sufficient to form large single crystals, this is not the case for F(64)PcCu. Its crystal structure was determined by X-ray analysis and linked to the electronic properties determined by electron paramagnetic resonance (EPR). The findings are corroborated by density functional theory (DFT) computations, which agree well with the experiment. X-band continuous-wave EPR spectra of undiluted F(64)PcCu powder, indicate the existence of isolated metal centers. The electron-withdrawing effect of the perfluoroalkyl (R(f)) groups significantly enhances the complexes solubility in organic solvents like alcohols, including via their axial coordination. This coordination is confirmed by X-band (1)H HYSCORE experiments and is also seen in the solid state via the X-ray structure. Detailed X-band CW-EPR, X-band Davies and Mims ENDOR, and W-band electron spin-echo-detected EPR studies of F(64)PcCu in ethanol allow the determination of the principal g values and the hyperfine couplings of the metal, nitrogen, and fluorine nuclei. Comparison of the g and metal hyperfine values of F(64)PcCu and other PcCu complexes in different matrices reveals a dominant effect of the matrix on these EPR parameters, while variations in the ring substituents have only a secondary effect. The relatively strong axial coordination occurs despite the diminished covalency of the C-N bonds and potentially weakening Jahn-Teller effects. Surprisingly, natural abundance (13)C HYSCORE signals could be observed for a frozen ethanol solution of F(64)PcCu. The (13)C nuclei contributing to the HYSCORE spectra could be identified as the pyrrole carbons by means of DFT. Finally, (19)F ENDOR and easily observable paramagnetic NMR were found to relate well to the DFT computations, revealing negligible isotropic hyperfine (Fermi contact) contributions. The single-site isolation in solution and solid state and the relatively strong coordination of axial ligands, both attributed to the introduction of R(f) groups, are features important for materials and catalyst design.

Long-range solid-state ordering and high geometric distortions induced in phthalocyanines by small fluoroalkyl groups.

Electron-withdrawing alpha-CF(3) groups sterically induce severe geometric distortions and long-range solid-state ordering in protio and catalytically active micro-oxo iron phthalocyanine.

Rational design of a reactive yet stable organic-based photocatalyst.

Zinc perfluoro-fluoroalkyl-phthalocyanine, synthesized in high yield, does not exhibit electron loss, does not aggregate in solution, is photostable and produces (1)O(2) in very high quantum yields. Aerobic photo-oxygenation of an external substrate occurs without catalyst self-oxidation. The encapsulation of a metal center in a refractory organic environment could guide the design of other viable catalysts for oxygenation of substrates either for synthesis or for oxidative destruction of organic or biological molecules, under reaction conditions that include the use of only air and light.

Enhanced acidity, photophysical properties and liposome binding of perfluoroalkylated phthalocyanines lacking C-H bonds.

The acid-base, spectroscopic, photophysical and liposome-binding properties of the recently synthesized free base, 29H,31H,1,4,8,11,15,18,22,25-octafluoro-2,3,9,10,16,17,23, 24-octakisperfluoro(isopropyl) phthalocyanine, F64PcH2, are reported. The perfluoroalkylation of the phthalocyanine core renders the hydrogen atoms acidic, with a pK(a) = 6. The F64Pc(-2) dianion is detected already at pH 3, by singular-value decomposition analysis of electronic spectra. F64Pc(-2) generates 1O2 with quantum yields phi(delta) = 0.252 (in MeOH) and 0.019 in liposomes. Metallation of the Pc macrocycle to yield F64PcZn increases phi(delta) to 0.606 and 0.126 in MeOH and liposomes, respectively. Surprisingly, F64Pc(-2) (but not F64PcH2 or F64PcZn) binds strongly to liposomes, with a binding constant K(b) = 25 (mg/mL)(-1). The fully protonated F64PcH2, but not the zwitterionic F64Pc(-2), might favor hydrogen bonding, thus reducing its lipophilicity. Similarly, the Lewis acidity of Zn in F64PcZn, and thus its ability to bind water within a hydrophobic perfluoroalkyl pocket, is significantly enhanced by the fluorinated substituents.

Effects of tris(pyrazolyl)borato ligand substituents on dioxygen activation and stabilization by copper compounds.

Dinuclear [Cu2(mu-O)2(Tp(R,R')2] complexes, analogues of the active site of oxyhemocyanin, are theoretically studied, and the effect of the substituents of the tris(pyrazolyl)borate ligands, Tp(R,R'), is analyzed. Density functional theory calculations reveal that the type of bridging oxygen, peroxo, or bisoxo is strongly influenced by the nature and position of the R substituents because of variable substituent...bridging oxygen interactions, as well as electronic effects. The electronic effects of ligands at the 5 position are not significant, but peroxo complexes are favored by electron-withdrawing groups at the 3 position while bisoxo ones are strongly sterically disfavored.