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A series of fluorescent probe molecules based on the commercially available trans-4-(4-(diethylamino)styryl)-N-methylpyridinium iodide (DAMPI) scaffold has been developed. The dynamic radii of these DAMPI-type probes covered a range of 5.8 to 10.1 Å and could be changed by varying the alkyl substituents on the amine donor group, with limited effect on the electronic properties. These probe molecules allow for the direct evaluation of the molecular accessibility into confined spaces, more specifically the micropore architecture of zeolite materials. Evaluation of industrially relevant zeolite materials with 8- (CHA), 10- (MFI) and 12-membered ring pores (FAU) showed that steric bulk influences the rate of adsorption, the amount of probe molecule taken up by the zeolite as well as the interaction of the probe molecule with the zeolite material. Furthermore, a positive linear correlation is found between the pore-probe size difference and total probe uptake by the zeolite. The absorption spectra of each probe molecule within the zeolites show that this DAMPI-type compound is chemically bound to the zeolite's acid sites. The new approach shows the general principle of determining size-accessibility relationships in microporous solids with a series of fluorescent probes of systematically tunable size.

Bio-based furanics can be aromatized efficiently by sequential Diels-Alder (DA) addition and hydrogenation steps followed by tandem catalytic aromatization. With a combination of zeolite H-Y and Pd/C, the hydrogenated DA adduct of 2-methylfuran and maleic anhydride can thus be aromatized in the liquid phase and, to a certain extent, decarboxylated to give high yields of the aromatic products 3-methylphthalic anhydride and o- and m-toluic acid. Here, it is shown that a variation in the acidity and textural properties of the solid acid as well as bifunctionality offers a handle on selectivity toward aromatic products. The zeolite component was found to dominate selectivity. Indeed, a linear correlation is found between 3-methylphthalic anhydride yield and the product of (strong acid/total acidity) and mesopore volume of H-Y, highlighting the need for balanced catalyst acidity and porosity. The efficient coupling of the dehydration and dehydrogenation steps by varying the zeolite-to-Pd/C ratio allowed the competitive decarboxylation reaction to be effectively suppressed, which led to an improved 3-methylphthalic anhydride/total aromatics selectivity ratio of 80 % (89 % total aromatics yield). The incorporation of Pd nanoparticles in close proximity to the acid sites in bifunctional Pd/H-Y catalysts also afforded a flexible means to control aromatic products selectivity, as further demonstrated in the aromatization of hydrogenated DA adducts from other diene/dienophile combinations., (© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Lignin is an attractive renewable feedstock for aromatic bulk and fine chemicals production, provided that suitable depolymerization procedures are developed. Here, we describe a tandem catalysis strategy for ether linkage cleavage within lignin, involving ether hydrolysis by water-tolerant Lewis acids followed by aldehyde decarbonylation by a Rh complex. In situ decarbonylation of the reactive aldehydes limits loss of monomers by recondensation, a major issue in acid-catalyzed lignin depolymerization. Rate of hydrolysis and decarbonylation were matched using lignin model compounds, allowing the method to be successfully applied to softwood, hardwood, and herbaceous dioxasolv lignins, as well as poplar sawdust, to give the anticipated decarbonylation products and, rather surprisingly, 4-(1-propenyl)phenols. Promisingly, product selectivity can be tuned by variation of the Lewis-acid strength and lignin source., (© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Lignin is an abundant biopolymer with a high carbon content and high aromaticity. Despite its potential as a raw material for the fuel and chemical industries, lignin remains the most poorly utilised of the lignocellulosic biopolymers. Effective valorisation of lignin requires careful fine-tuning of multiple "upstream" (i.e., lignin bioengineering, lignin isolation and "early-stage catalytic conversion of lignin") and "downstream" (i.e., lignin depolymerisation and upgrading) process stages, demanding input and understanding from a broad array of scientific disciplines. This review provides a "beginning-to-end" analysis of the recent advances reported in lignin valorisation. Particular emphasis is placed on the improved understanding of lignin's biosynthesis and structure, differences in structure and chemical bonding between native and technical lignins, emerging catalytic valorisation strategies, and the relationships between lignin structure and catalyst performance., (© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

In this series of articles, the board members of ChemSusChem discuss recent research articles that they consider of exceptional quality and importance for sustainability. This entry features Dr. Pieter Bruijnincx, who discusses bio-based approaches to new and existing chemicals for large-scale polymer applications, highlighting that the development of methodologies to obtain key monomers from biomass leads to new chemistry, aids the transition to a more sustainable chemical industry, and fosters new interdisciplinary approaches., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Renewable aromatics can be conveniently synthesized from furanics by introducing an intermediate hydrogenation step in the Diels-Alder (DA) aromatization route, to effectively block retro-DA activity. Aromatization of the hydrogenated DA adducts requires tandem catalysis, using a metal-based dehydrogenation catalyst and solid acid dehydration catalyst in toluene. Herein it is demonstrated that the hydrogenated DA adducts can instead be conveniently converted into renewable aromatics with up to 80% selectivity in a solid-phase reaction with shorter reaction times using only an acidic zeolite, that is, without solvent or dehydrogenation catalyst. Hydrogenated adducts from diene/dienophile combinations of (methylated) furans with maleic anhydride are efficiently converted into renewable aromatics with this new route. The zeolite H-Y was found to perform the best and can be easily reused after calcination., (© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Large zeolite crystals of ferrierite have been used to study the deactivation, at the single particle level, of the alkyl isomerisation catalysis of oleic acid and elaidic acid by a combination of visible micro-spectroscopy and fluorescence microscopy (both polarised wide-field and confocal modes). The large crystals did show the desired activity, albeit only traces of the isomerisation product were obtained and low conversions were achieved compared to commercial ferrierite powders. This limited activity is in line with their lower external non-basal surface area, supporting the hypothesis of pore mouth catalysis. Further evidence for the latter comes from visible micro-spectroscopy, which shows that the accumulation of aromatic species is limited to the crystal edges, while fluorescence microscopy strongly suggests the presence of polyenylic carbocations. Light polarisation associated with the spatial resolution of fluorescence microscopy reveals that these carbonaceous deposits are aligned only in the larger 10-MR channels of ferrierite at all crystal edges. The reaction is hence further limited to these specific pore mouths., (© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.)

A novel route for the production of renewable aromatic chemicals, particularly substituted phthalic acid anhydrides, is presented. The classical two-step approach to furanics-derived aromatics via Diels-Alder (DA) aromatization has been modified into a three-step procedure to address the general issue of the reversible nature of the intermediate DA addition step. The new sequence involves DA addition, followed by a mild hydrogenation step to obtain a stable oxanorbornane intermediate in high yield and purity. Subsequent one-pot, liquid-phase dehydration and dehydrogenation of the hydrogenated adduct using a physical mixture of acidic zeolites or resins in combination with metal on a carbon support then allows aromatization with yields as high as 84 % of total aromatics under relatively mild conditions. The mechanism of the final aromatization reaction step unexpectedly involves a lactone as primary intermediate., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Glycerol is an attractive renewable building block for the synthesis of polyglycerols, which find application in the cosmetic and pharmaceutical industries. The selective etherification of glycerol to higher oligomers was studied in the presence of CaO colloids and the data are compared with those obtained from NaOH and CaO. The materials were prepared by dispersing CaO, CaCO3 , or Ca(OH)2 onto a carbon nanofiber (CNF) support. Colloidal nanoparticles were subsequently dispensed from the CNF into the reaction mixture to give CaO colloids that have a higher activity than equimolar amounts of bulk CaO and NaOH. Optimization of the reaction conditions allowed us to obtain a product with Gardner color number <2, containing no acrolein and minimal cyclic byproducts. The differences in the CaO colloids originating from CNF and bulk CaO were probed using light scattering and conductivity measurements. The results confirmed that the higher activity of the colloids originating from CaO/CNF was due to their more rapid formation and smaller size compared with colloids from bulk CaO. We thus have developed a practical method for the synthesis of polyglycerols containing low amounts of Ca., (© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.)

The catalytic hydrogenation of levulinic acid, a key platform molecule in many biorefinery schemes, into γ-valerolactone is considered as one of the pivotal reactions to convert lignocellulose-based biomass into renewable fuels and chemicals. Here we report on the development of highly active, selective and stable supported metal catalysts for this reaction and on the beneficial effects of metal nano-alloying. Bimetallic random alloys of gold-palladium and ruthenium-palladium supported on titanium dioxide are prepared with a modified metal impregnation method. Gold-palladium/titanium dioxide shows a marked,~27-fold increase in activity (that is, turnover frequency of 0.1 s(-1)) compared with its monometallic counterparts. Although ruthenium-palladium/titanium dioxide is not only exceptionally active (that is, turnover frequency of 0.6 s(-1)), it shows excellent, sustained selectivity to γ-valerolactone (99%). The dilution and isolation of ruthenium by palladium is thought to be responsible for this superior catalytic performance. Alloying, furthermore, greatly improves the stability of both supported nano-alloy catalysts.

Catechol intradiol dioxygenation is a unique reaction catalyzed by iron-dependent enzymes and non-heme iron(III) complexes. The mechanism by which these systems activate dioxygen in this important metabolic process remains controversial. Using a combination of kinetic measurements and computational modelling of multiple iron(III) catecholato complexes, we have elucidated the catechol cleavage mechanism and show that oxygen binds the iron center by partial dissociation of the substrate from the iron complex. The iron(III) superoxide complex that is formed subsequently attacks the carbon atom of the substrate by a rate-determining C-O bond formation step., (© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)

Silica-magnesia (Si/Mg=1:1) catalysts were studied in the one-pot conversion of ethanol to butadiene. The catalyst synthesis method was found to greatly influence morphology and performance, with materials prepared through wet-kneading performing best both in terms of ethanol conversion and butadiene yield. Detailed characterization of the catalysts synthesized through co-precipitation or wet-kneading allowed correlation of activity and selectivity with morphology, textural properties, crystallinity, and acidity/basicity. The higher yields achieved with the wet-kneaded catalysts were attributed to a morphology consisting of SiO2 spheres embedded in a thin layer of MgO. The particle size of the SiO2 catalysts also influenced performance, with catalysts with smaller SiO2 spheres showing higher activity. Temperature-programmed desorption (TPD) measurements showed that best butadiene yields were obtained with SiO2-MgO catalysts characterized by an intermediate amount of acidic and basic sites. A Hammett indicator study showed the catalysts' pK(a) value to be inversely correlated with the amount of dehydration by-products formed. Butadiene yields could be further improved by the addition of 1 wt% of CuO as promoter to give butadiene yields and selectivities as high as 40% and 53%, respectively. The copper promoter boosts the production of the acetaldehyde intermediate changing the rate-determining step of the process. TEM-energy-dispersive X-ray (EDX) analyses showed CuO to be present on both the SiO2 and MgO components. UV/Vis spectra of promoted catalysts in turn pointed at the presence of cluster-like CuO species, which are proposed to be responsible for the increased butadiene production., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A one-pot method has been developed for the oxidative cleavage of internal alkenes into aldehydes by using 0.5 mol% of the nonheme iron complex [Fe(OTf)2(mix-bpbp)] (bpbp=N,N'-bis(2-picolyl)-2,2'-bipyrrolidine) as catalyst and 1.5 equivalents of hydrogen peroxide and 1 equivalent of sodium periodate as oxidants. A mixture of diastereomers of the chiral bpbp ligand can be used, thereby omitting the need for resolution of its optically active components. The cleavage reaction can be performed in one pot within 20 h and under ambient conditions. Addition of water after the epoxidation, acidification and subsequent pH neutralization are crucial to perform the epoxidation, hydrolysis, and subsequent diol cleavage in one pot. High aldehyde yields can be obtained for the cleavage of internal aliphatic double bonds with cis and trans configuration (86-98%) and unsaturated fatty acids and esters (69-96%). Good aldehyde yields are obtained in reactions of trisubstituted and terminal alkenes (62-63%). The products can be easily isolated by a simple extraction step with an organic solvent. The presented protocol involves a lower catalyst loading than conventional methods based on Ru or Os. Also, hydrogen peroxide can be used as the oxidant in this case, which is often disproportionated by second- and third-row metals. By using only mild oxidants, overoxidation of the aldehyde to the carboxylic acid is prevented., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The development of new and improved processes for the synthesis of bio-based chemicals is one of the scientific challenges of our time. These new discoveries are not only important from an environmental point of view, but also represent an important economic opportunity, provided that the developed processes are selective and efficient. Bioethanol is currently produced from renewable resources in large amounts and, in addition to its use as biofuel, holds considerable promise as a building block for the chemical industry. Indeed, further improvements in production, both in terms of efficiency and feedstock selection, will guarantee availability at competitive prices. The conversion of bioethanol into commodity chemicals, in particular direct 'drop-in' replacements is, therefore, becoming increasingly attractive, provided that the appropriate (catalytic) technology is in place. The production of green and renewable 1,3-butadiene is a clear example of this approach. The Lebedev process for the one-step catalytic conversion of ethanol to butadiene has been known since the 1930s and has been applied on an industrial scale to produce synthetic rubber. Later, the availability of low-cost oil made it more convenient to obtain butadiene from petrochemical sources. The desire to produce bulk chemicals in a sustainable way and the availability of low-cost bioethanol in large volumes has, however, resulted in a renaissance of this old butadiene production process. This paper reviews the catalytic aspects associated with the synthesis of butadiene via the Lebedev process, as well as the production of other, mechanistically related bulk chemicals that can be obtained from (bio)ethanol., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Neither the routes through which humin byproducts are formed, nor their molecular structure have yet been unequivocally established. A better understanding of the formation and physicochemical properties of humins, however, would aid in making biomass conversion processes more efficient. Here, an extensive multiple-technique-based study of the formation, molecular structure, and morphology of humins is presented as a function of sugar feed, the presence of additives (e.g., 1,2,4-trihydroxybenzene), and the applied processing conditions. Elemental analyses indicate that humins are formed through a dehydration pathway, with humin formation and levulinic acid yields strongly depending on the processing parameters. The addition of implied intermediates to the feedstocks showed that furan and phenol compounds formed during the acid-catalyzed dehydration of sugars are indeed included in the humin structure. IR spectra, sheared sum projections of solid-state 2DPASS (13) C NMR spectra, and pyrolysis GC-MS data indicate that humins consist of a furan-rich polymer network containing different oxygen functional groups. The structure is furthermore found to strongly depend on the type of feedstock. A model for the molecular structure of humins is proposed based on the data presented., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The catalyst system prepared in situ from iron(III) salts, tris(2-pyridylmethyl)amine and a base readily catalyses the intradiol dioxygenation of pyrocatechol in methanol, to primarily afford the half-methyl ester of muconic acid. Dimethyl adipate is obtained by the subsequent, one-step catalytic hydrogenation/esterification, thus providing a green route to this important nylon precursor.

With dwindling reserves of fossil feedstock as a resource for chemicals production, the fraction of chemicals and energy supplied by alternative, renewable resources, such as lignin, can be expected to increase in the foreseeable future. Here, we demonstrate a catalytic process to valorize lignin (exemplified with kraft, organosolv, and sugarcane bagasse lignin) using a mixture of cheap, bio-renewable ethanol and water as solvent. Ethanol/water mixtures readily solubilize lignin under moderate temperatures and pressures with little residual solids. The molecular weight of the dissolved lignins was shown to be reduced by gel permeation chromatography and quantitative HSQC NMR methods. The use of liquid-phase reforming of the solubilized lignin over a Pt/Al(2)O(3) catalyst at 498 K and 58 bar is introduced to yield up to 17 % combined yield of monomeric aromatic oxygenates such as guaiacol and substituted guaiacols generating hydrogen as a useful by-product. Reduction of the lignin dissolved in ethanol/water using a supported transition metal catalyst at 473 K and 30 bar hydrogen yields up to 6 % of cyclic hydrocarbons and aromatics., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The cost- and material-efficient development of next-generation catalysts would benefit greatly from a molecular-level understanding of the interaction between reagents and catalysts in chemical conversion processes. Here, we trace the conversion of alkene and glycol in single zeolite catalyst particles with unprecedented chemical and spatial resolution. Combined nonlinear Raman and two-photon fluorescence spectromicroscopies reveal that alkene activation constitutes the first reaction step toward glycol etherification and allow us to determine the activation enthalpy of the resulting carbocation formation. Considerable inhomogeneities in local reactivity are observed for micrometer-sized catalyst particles. Product ether yields observed on the catalyst are ca. 5 times higher than those determined off-line. Our findings are relevant for other heterogeneous catalytic processes and demonstrate the immense potential of novel nonlinear spectromicroscopies for catalysis research., (© 2011 American Chemical Society)

The newly synthesized dinuclear complex [Fe(III)(2)(μ-OH)(2)(bik)(4)](NO(3))(4) (1) (bik, bis(1-methylimidazol-2-yl)ketone) shows rather short Fe···Fe (3.0723(6) Å) and Fe-O distances (1.941(2)/1.949(2) Å) compared to other unsupported Fe(III)(2)(μ-OH)(2) complexes. The bridging hydroxide groups of 1 are strongly hydrogen-bonded to a nitrate anion. The (57)Fe isomer shift (δ = 0.45 mm s(-1)) and quadrupole splitting (ΔE(Q) = 0.26 mm s(-1)) obtained from Mössbauer spectroscopy are consistent with the presence of two identical high-spin iron(III) sites. Variable-temperature magnetic susceptibility studies revealed antiferromagnetic exchange (J = 35.9 cm(-1) and H = JS(1)·S(2)) of the metal ions. The optimized DFT geometry of the cation of 1 in the gas phase agrees well with the crystal structure, but both the Fe···Fe and Fe-OH distances are overestimated (3.281 and 2.034 Å, respectively). The agreement in these parameters improves dramatically (3.074 and 1.966 Å) when the hydrogen-bonded nitrate groups are included, reducing the value calculated for J by 35%. Spontaneous reduction of 1 was observed in methanol, yielding a blue [Fe(II)(bik)(3)](2+) species. Variable-temperature magnetic susceptibility measurements of [Fe(II)(bik)(3)](OTf)(2) (2) revealed spin-crossover behavior. Thermal hysteresis was observed with 2, due to a loss of cocrystallized solvent molecules, as monitored by thermogravimetric analysis. The hysteresis disappears once the solvent is fully depleted by thermal cycling. [Fe(II)(bik)(3)](OTf)(2) (2) catalyzes the oxidation of alkanes with t-BuOOH. High selectivity for tertiary C-H bond oxidation was observed with adamantane (3°/2° value of 29.6); low alcohol/ketone ratios in cyclohexane and ethylbenzene oxidation, a strong dependence of total turnover number on the presence of O(2), and a low retention of configuration in cis-1,2-dimethylcyclohexane oxidation were observed. Stereoselective oxidation of olefins with dihydrogen peroxide yielding epoxides was observed under both limiting oxidant and substrate conditions.

The low-spin 5d(6) Ir(III) organometallic half-sandwich complexes [(η(5)-Cp(x))Ir(XY)Cl](0/+), Cp(x) = Cp*, tetramethyl(phenyl)cyclopentadienyl (Cp(xph)), or tetramethyl(biphenyl)cyclopentadienyl (Cp(xbiph)), XY = 1,10-phenanthroline (4-6), 2,2'-bipyridine (7-9), ethylenediamine (10 and 11), or picolinate (12-14), hydrolyze rapidly. Complexes with N,N-chelating ligands readily form adducts with 9-ethylguanine but not 9-ethyladenine; picolinate complexes bind to both purines. Cytotoxic potency toward A2780 human ovarian cancer cells increases with phenyl substitution on Cp*: Cp(xbiph) > Cp(xph) > Cp*; Cp(xbiph) complexes 6 and 9 have submicromolar activity. Guanine residues are preferential binding sites for 4-6 on plasmid DNA. Hydrophobicity (log P), cell and nucleus accumulation of Ir correlate with cytotoxicity, 6 > 5 > 4; they distribute similarly within cells. The ability to displace DNA intercalator ethidium bromide from DNA correlates with cytotoxicity and viscosity of Ir-DNA adducts. The hydrophobicity and intercalative ability of Cp(xph) and Cp(xbiph) make a major contribution to the anticancer potency of their Ir(III) complexes.

The etherification of biomass-based alcohols with various linear alpha-olefins under solvent-free conditions was followed in a space- and time-resolved manner on 9 microm large H-Beta zeolite crystals by confocal fluorescence microscopy. This allowed us to visualize the interaction with the substrate and distribution of the coke products into the catalyst at the level of an individual zeolite crystal during the etherification process. The spectroscopic information obtained on the micrometer-scale zeolite was in line with the results obtained with bulk characterization techniques and further confirmed by the catalytic results obtained both for micrometer-scale and nanoscale zeolites. This allowed us to explain the influence of the substrate type (glycerol, glycols, and alkenes) and zeolite properties (Si/Al ratio and particle size) on the etherification activity. The etherification of the biomass-based alcohols takes place mainly on the external surface of the zeolite particles. The gradual blockage of the external surface of the zeolite results in a partial or total loss of etherification activity. The deactivation could be attributed to olefin oligomerization. The high conversions obtained in the etherification of 1,2-propylene glycol with long linear alkenes (up to 80%) and the pronounced deactivation of the zeolite observed in the etherification of glycerol with long linear alkenes (max. 20% conversion) were explained by the spectroscopic measurements and is due to differences in the adsorption, i.e., in the center of the zeolite particle for glycerol and on the external surface in the case of glycols.

Thiolate ligand oxygenation is believed to activate cytotoxic half-sandwich [(eta(6)-arene)Ru(en)(SR)](+) complexes toward DNA binding. We have made detailed comparisons of the nature of the Ru-S bond in the parent thiolato complexes and mono- (sulfenato) and bis- (sulfinato) oxygenated species including the influence of substituents on the sulfur and arene. Sulfur K-edge XAS indicates that S(3p) donation into the Ru(4d) manifold depends strongly on the oxidation state of the sulfur atom, whereas Ru K-edge data suggest little change at the metal center. DFT results are in agreement with the experimental data and allow a more detailed analysis of the electronic contributions to the Ru-S bond. Overall, the total ligand charge donation to the metal center remains essentially unchanged upon ligand oxygenation, but the origin of the donation differs markedly. In sulfenato complexes, the terminal oxo group makes a large contribution to charge donation and even small electronic changes in the thiolato complexes are amplified upon ligand oxygenation, an observation which carries direct implications for the biological activity of this family of complexes. Details of Ru-S bonding in the mono-oxygenated complexes suggest that these should be most susceptible to ligand exchange, yet only if protonation of the terminal oxo group can occur. The potential consequences of these results for biological activation are discussed.

Iron-containing enzymes are one of Nature's main means of effecting key biological transformations. The mononuclear non-heme iron oxygenases and oxidases have received the most attention recently, primarily because of the recent availability of crystal structures of many different enzymes and the stunningly diverse oxidative transformations that these enzymes catalyze. The wealth of available structural data has furthermore established the so-called 2-His-1-carboxylate facial triad as a new common structural motif for the activation of dioxygen. This superfamily of mononuclear iron(ii) enzymes catalyzes a wide range of oxidative transformations, ranging from the cis-dihydroxylation of arenes to the biosynthesis of antibiotics such as isopenicillin and fosfomycin. The remarkable scope of oxidative transformations seems to be even broader than that associated with oxidative heme enzymes. Not only are many of these oxidative transformations of key biological importance, many of these selective oxidations are also unprecedented in synthetic organic chemistry. In this critical review, we wish to provide a concise background on the chemistry of the mononuclear non-heme iron enzymes characterized by the 2-His-1-carboxylate facial triad and to discuss the many recent developments in the field. New examples of enzymes with unique reactivities belonging to the superfamily have been reported. Furthermore, key insights into the intricate mechanistic details and reactive intermediates have been obtained from both enzyme and modeling studies. Sections of this review are devoted to each of these subjects, i.e. the enzymes, biomimetic models, and reactive intermediates (225 references).

Medicinal inorganic chemistry can exploit the unique properties of metal ions for the design of new drugs. This has, for instance, led to the clinical application of chemotherapeutic agents for cancer treatment, such as cisplatin. The use of cisplatin is, however, severely limited by its toxic side-effects. This has spurred chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. Recent trends in the field are discussed in this review. These include the more selective delivery and/or activation of cisplatin-related prodrugs and the discovery of new non-covalent interactions with the classical target, DNA. The use of the metal as scaffold rather than reactive centre and the departure from the cisplatin paradigm of activity towards a more targeted, cancer cell-specific approach, a major trend, are discussed as well. All this, together with the observation that some of the new drugs are organometallic complexes, illustrates that exciting times lie ahead for those interested in 'metals in medicine'.

The Rieske dioxygenases are a group of non-heme iron enzymes, which catalyze the stereospecific cis-dihydroxylation of its substrates. Herein, we report the iron(II) coordination chemistry of the ligands 3,3-bis(1-methylimidazol-2-yl)propionate (L1) and its neutral propyl ester analogue propyl 3,3-bis(1-methylimidazol-2-yl)propionate (PrL1). The molecular structures of two iron(II) complexes with PrL1 were determined and two different coordination modes of the ligand were observed. In [Fe(II)(PrL1)(2)](BPh(4))(2) (3) the ligand is facially coordinated to the metal with an N,N,O donor set, whereas in [Fe(II)(PrL1)(2)(MeOH)(2)](OTf)(2) (4) a bidentate N,N binding mode is found. In 4, the solvent molecules are in a cis arrangement with respect to each other. Complex 4 is a close structural mimic of the crystallographically characterized non-heme iron(II) enzyme apocarotenoid-15-15'-oxygenase (APO). The mechanistic features of APO are thought to be similar to those of the Rieske oxygenases, the original inspiration for this work. The non-heme iron complexes [Fe(II)(PrL1)(2)](OTf)(2) (2) and [Fe(II)(PrL1)(2)](BPh(4))(2) (3) were tested in olefin oxidation reactions with H(2)O(2) as the terminal oxidant. Whereas 2 was an active catalyst and both epoxide and cis-dihydroxylation products were observed, 3 showed negligible activity under the same conditions, illustrating the importance of the anion in the reaction.

Copper(II) complexes of the potentially tripodal N,N,O ligand 3,3-bis(1-methylimidazol-2-yl)propionate (L1) and its conjugate acid HL1 have been synthesised and structurally and spectroscopically characterised. The reaction of equimolar amounts of ligand and CuII resulted in the complexes [Cu(L1)]n(X)n (X=OTf-, PF6(-); n=1,2), for which a new bridging coordination mode of L1 is inferred. Although these complexes showed moderate catecholase activity in the oxidation of 3,5-di-tert-butylcatechol, surprising reactivity with the pseudo-substrate tetrachlorocatechol was observed. A chloranilato-bridged dinuclear CuII complex was isolated from the reaction of [Cu(L1)]n(PF6)n with tetrachlorocatechol. This stoichiometric oxidative double dehalogenation of tetrachlorocatechol to chloranilic acid by a biomimetic copper(II) complex is unprecedented. The crystal structure of the product, [Cu2(ca)Cl2(HL1)2], shows a bridging bis-bidentate chloranilato (ca) ligand and ligand L1 coordinated as its conjugate acid (HL1) in a tridentate fashion. Magnetic susceptibility studies revealed weak antiferromagnetic coupling (J= -35 cm(-1)) between the two copper centres in the dinuclear complex. Dissolution of the green complex [Cu2(ca)Cl2(HL1)2] resulted in the formation of new pink-purple mononuclear compound [Cu(ca)(HL1)(H2O)], the crystal structure of which was determined. It showed a terminal bidentate chloranilato ligand and N,N-bidentate coordination of ligand HL1, which illustrates the flexible coordination chemistry of ligand L1.

The coordination chemistry of the 2-His-1-carboxylate facial triad mimics 3,3-bis(1-methylimidazol-2-yl)propionate (MIm(2)Pr) and 3,3-bis(1-ethyl-4-isopropylimidazol-2-yl) propionate (iPrEtIm(2)Pr) towards ZnCl(2) was studied both in solution and in the solid state. Different coordination modes were found depending both on the stoichiometry and on the ligand that was employed. In the 2:1 ligand-to-metal complex [Zn(MIm(2)Pr)(2)], the ligand coordinates in a tridentate, tripodal N,N,O fashion similar to the 2-His-1-carboxylate facial triad. However, the 1:1 ligand-to-metal complexes [Zn(MIm(2)Pr)Cl(H(2)O)] and [Zn(iPrEtIm(2)Pr)Cl] were crystallographically characterized and found to be polymeric in nature. A new, bridging coordination mode of the ligands was observed in both structures comprising N,N-bidentate coordination of the ligand to one zinc atom and O-monodentate coordination to a zinc second atom. A rather unique transformation of pyruvate into oxalate was found with [Zn(MIm(2)Pr)Cl], which resulted in the isolation of the new, oxalato bridged zinc coordination polymer [Zn(2)(MIm(2)Pr)(2)(ox)].6H(2)O, the structure of which was established by X-ray crystal structure determination.

The structural and spectroscopic characterization of mononuclear iron(III)-catecholato complexes of ligand L4 (methyl bis(1-methylimidazol-2-yl)(2-hydroxyphenyl)methyl ether, HL4) are described, which closely mimic the enzyme-substrate complex of the intradiol-cleaving catechol dioxygenases. The tridentate, tripodal monoanionic ligand framework of L4 incorporates one phenolato and two imidazole donor groups and thus well reproduces the His2Tyr endogenous donor set. In fact, regarding the structural features of [FeIII(L4)(tcc)(H2O)] (5.H2O, tcc = tetrachlorocatechol) in the solid state, the complex constitutes the closest structural model reported to date. The iron(III)-catecholato complexes mimic both the structural features of the active site and its spectroscopic characteristics. As part of its spectroscopic characterization, the electron paramagnetic resonance (EPR) spectra were successfully simulated using a simple model that accounts for D strain. The simulation procedure showed that the observed g = 4.3 line is an intrinsic part of the EPR envelope of the studied complexes and should not necessarily be attributed to a highly rhombic impurity. [FeIII(L4)(dtbc)(H2O)] (dtbc = 3,5-di-tert-butylcatechol) was studied with respect to its dioxygen reactivity, and oxidative cleavage of the substrate was observed. Intradiol- and extradiol-type cleavage products were found in roughly equal amounts. This shows that an accurate structural model of the first-coordination sphere of the active site is not sufficient for obtaining regioselectivity.

Mononuclear iron(II)- and iron(III)-catecholato complexes with three members of a new 3,3-bis(1-alkylimidazol-2-yl)propionate ligand family have been synthesized as models of the active sites of the extradiol cleaving catechol dioxygenases. These enzymes are part of the superfamily of dioxygen-activating mononuclear non-heme iron enzymes that feature the so-called 2-His-1-carboxylate facial triad. The tridentate, tripodal, and monoanionic ligands used in this study include the biologically relevant carboxylate and imidazole donor groups. The structure of the mononuclear iron(III)-tetrachlorocatecholato complex [Fe(L3)(tcc)(H2O)] was determined by single-crystal X-ray diffraction, which shows a facial N,N,O capping mode of the ligand. For the first time, a mononuclear iron complex has been synthesized, which is facially capped by a ligand offering a tridentate Nim,Nim,Ocarb donor set, identical to the endogenous ligands of the 2-His-1-carboxylate facial triad. The iron complexes are five-coordinate in noncoordinating media, and the vacant coordination site is accessible for Lewis bases, e.g., pyridine, or small molecules such as dioxygen. The iron(II)-catecholato complexes react with dioxygen in two steps. In the first reaction the iron(II)-catecholato complexes rapidly convert to the corresponding iron(III) complexes, which then, in a second slow reaction, exhibit both oxidative cleavage and auto-oxidation of the substrate. Extradiol and intradiol cleavage are observed in noncoordinating solvents. The addition of a proton donor results in an increase in extradiol cleavage. The complexes add a new example to the small group of synthetic iron complexes capable of eliciting extradiol-type cleavage and provide more insight into the factors determining the regioselectivity of the enzymes.

The stabilization of a mononuclear copper(II) complex with one MIm2Pr ligand [MIm2Pr = 3,3-bis(1-methylimidazol-2-yl)propionate] in the supercages of zeolite Y was attempted, and the resulting materials were tested for their activity in oxidation catalysis. The preparation procedure yielded initially two species (labeled 1 and 2) within the pore system of the zeolite material, which differ in molecular structure and chemical composition as determined by UV/vis, ESR, IR, and XAFS spectroscopy. In species 1, the copper was found to be five-coordinated, with one MIm2Pr ligand in a facial-type NNO coordination toward copper, the other two coordination sites being occupied by oxygen atoms from either the zeolite framework and/or a water molecule. The total charge of this complex is 1+. In species 2, the copper is surrounded by two MIm2Pr ligands, both in a facial-type coordination mode, identical to the homogeneous Cu(MIm2Pr)2 complex. This neutral species 2 is easily washed out of the zeolite, whereas the mononuclear species 1 remains inside the zeolite material upon washing. The spectroscopic characteristics and activity for 3,5-di-tert-butylcatechol and benzyl alcohol oxidation of species 1 compared closely with that of the zeolite-immobilized Cu(histidine) complexes but differed from that of the homogeneous Cu(MIm2Pr)2 complex. It was therefore found that encapsulation in zeolite offers a route to stabilize a 5-fold-coordinated copper complex with novel catalytic properties. This 1:1 Cu(MIm2Pr) complex is not formed in solution.