Crystal Phase Effects on the Gas-Phase Ketonization of Small Carboxylic Acids over TiO2 Catalysts.

Invited for this month's cover is the group of Pieter Bruijnincx from Utrecht University. The image shows an imaginary police line-up of two molecules suspected to be involved as intermediates in the catalytic ketonization reaction. Based on the evidence collected, depicted on the pinboard on the wall, the scientist discusses the impact of all this with somebody interested in catalysis that converts waste, wastewater-derived volatile fatty acids in this case, to value-added circular chemicals. The Full Paper itself is available at 10.1002/cssc.202100721.

Crystal Phase Effects on the Gas-Phase Ketonization of Small Carboxylic Acids over TiO2 Catalysts.

The choice of TiO2 crystal phase (i. e., anatase, rutile, or brookite) greatly influences catalyst performance in the gas-phase ketonization of small volatile fatty acids, such as acetic acid and propionic acid. Rutile TiO2 was found to perform best, combining superior activity, as exemplified by an exceptional reaction rate of 141.8 mmol h-1 gcat -1 (at 425 °C and 24 h-1 ) with excellent ketone selectivity when propionic acid was used. Brookite, to the best of our knowledge never reported before as a viable ketonization catalyst, was found to outperform the well-studied anatase phase, but not rutile. Operando Fourier-transform IR spectroscopy measurements combined with on-line mass spectrometry showed that bidentate carboxylates were the most abundant surface species on the rutile and brookite surfaces, while on anatase both monodentate and bidentate carboxylates co-existed. The bidendate carboxylates were thought to be precursors to the active ketonization species, likely monodentate intermediates more prone to C-C coupling. Ketonization activity did not directly correlate with acidity; the observed, strong crystal phase effect did suggest that ketonization activity is influenced strongly by geometrical factors that determine the ease of formation of the relevant surface intermediates.

Scaling-Up of Bio-Oil Upgrading during Biomass Pyrolysis over ZrO2 /ZSM-5-Attapulgite.

Ex situ catalytic biomass pyrolysis was investigated at both laboratory and bench scale by using a zeolite ZSM-5-based catalyst for selectively upgrading the bio-oil vapors. The catalyst consisted of nanocrystalline ZSM-5, modified by incorporation of ZrO2 and agglomerated with attapulgite (ZrO2 /n-ZSM-5-ATP). Characterization of this material by means of different techniques, including CO2 and NH3 temperature-programmed desorption (TPD), NMR spectroscopy, UV/Vis microspectroscopy, and fluorescence microscopy, showed that it possessed the right combination of accessibility and acid-base properties for promoting the conversion of the bulky molecules formed by lignocellulose pyrolysis and their subsequent deoxygenation to upgraded liquid organic fractions (bio-oil). The results obtained at the laboratory scale by varying the catalyst-to-biomass ratio (C/B) indicated that the ZrO2 /n-ZSM-5-ATP catalyst was more efficient for bio-oil deoxygenation than the parent zeolite n-ZSM-5, producing upgraded bio-oils with better combinations of mass and energy yields with respect to the oxygen content. The excellent performance of the ZrO2 /n-ZSM-5-ATP system was confirmed by working with a continuous bench-scale plant. The scale-up of the process, even with different raw biomasses as the feedstock, reaction conditions, and operation modes, was in line with the laboratory-scale results, leading to deoxygenation degrees of approximately 60 % with energy yields of approximately 70 % with respect to those of the thermal bio-oil.

Dichomitus squalens partially tailors its molecular responses to the composition of solid wood.

White-rot fungi, such as Dichomitus squalens, degrade all wood components and inhabit mixed-wood forests containing both soft- and hardwood species. In this study, we evaluated how D. squalens responded to the compositional differences in softwood [guaiacyl (G) lignin and higher mannan content] and hardwood [syringyl/guaiacyl (S/G) lignin and higher xylan content] using semi-natural solid cultures. Spruce (softwood) and birch (hardwood) sticks were degraded by D. squalens as measured by oxidation of the lignins using 2D-NMR. The fungal response as measured by transcriptomics, proteomics and enzyme activities showed a partial tailoring to wood composition. Mannanolytic transcripts and proteins were more abundant in spruce cultures, while a proportionally higher xylanolytic activity was detected in birch cultures. Both wood types induced manganese peroxidases to a much higher level than laccases, but higher transcript and protein levels of the manganese peroxidases were observed on the G-lignin rich spruce. Overall, the molecular responses demonstrated a stronger adaptation to the spruce rather than birch composition, possibly because D. squalens is mainly found degrading softwoods in nature, which supports the ability of the solid wood cultures to reflect the natural environment.

Influence of Levulinic Acid Hydrogenation on Aluminum Coordination in Zeolite-Supported Ruthenium Catalysts: A 27 Al 3QMAS Nuclear Magnetic Resonance Study.

The influence of a highly oxygenated, polar protic reaction medium, that is, levulinic acid in 2-ethylhexanoic acid, on the dealumination of two zeolite-supported ruthenium catalysts, namely Ru/H-ß and Ru/H-ZSM-5, has been investigated by 27 Al triple-quantum magic-angle spinning nuclear magnetic resonance spectroscopy (3QMAS NMR). Upon use of these catalysts in the hydrogenation of levulinic acid, the heterogeneity in aluminum speciation is found to increase for both Ru/H-ZSM-5 and Ru/H-ß. For Ru/H-ZSM-5, the symmetric, tetrahedral framework aluminum species (FAL) were found to be mainly converted into distorted tetrahedral FAL species, with limited loss of aluminum to the solution by leaching. A severe loss of both FAL and extra-framework aluminum (EFAL) species into the liquid phase was observed for Ru/H-ß instead. The large decrease in tetrahedral FAL species, in particular, results in a significant decrease in strong acid sites, as corroborated by Fourier transform infrared spectroscopy (FT-IR). This decrease in acidity, evidence of the inferior stability of the strongly acidic sites in Ru/H-ß relative to Ru/H-ZSM-5 under the applied conditions, is considered as the main reason for differences seen in catalyst performance.

Experimental and computational evidence for the mechanism of intradiol catechol dioxygenation by non-heme iron(III) complexes.

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.

Effect of preparation method and CuO promotion in the conversion of ethanol into 1,3-butadiene over SiO2-MgO catalysts.

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.

Catalytic oxidative cleavage of catechol by a non-heme iron(III) complex as a green route to dimethyl adipate.

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.

Chemocatalytic conversion of ethanol into butadiene and other bulk chemicals.

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.

Mono- and dinuclear iron complexes of bis(1-methylimidazol-2-yl)ketone (bik): structure, magnetic properties, and catalytic oxidation studies.

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.

Organometallic half-sandwich iridium anticancer complexes.

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.

Influence of oxygenation on the reactivity of ruthenium-thiolato bonds in arene anticancer complexes: insights from XAS and DFT.

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.

Mononuclear non-heme iron enzymes with the 2-His-1-carboxylate facial triad: recent developments in enzymology and modeling studies.

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).

Iron(II) complexes with bio-inspired N,N,O ligands as oxidation catalysts: olefin epoxidation and cis-dihydroxylation.

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.

New trends for metal complexes with anticancer activity.

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'.

Iron(III)-catecholato complexes as structural and functional models of the intradiol-cleaving catechol dioxygenases.

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.