Gallium Compounds Research Articles

SYNTHESIS OF GALLIUM COMPLEXES OF TERT-BUTYLSUBSTITUTED ACYCLIC AND CYCLIC COMPOUNDS BASED ON 3,5-DIAMINO-1,2,4-TRIAZOLE

Synthetic methods of organic chemistry which are currently available in scientific literature allow obtaining a large number macroheterocycles with structurally different internal coordination cavities. They also provide a number of convenient ways to attach to a macrocyclic platform various biologically active heterocyclic fragments such as guanazol. This paper discusses the synthesis and composition of gallium complexes of cyclic and acyclic compounds based on 3,5-diamino-1H-1,2,4-triazol (guanazol), which is itself widely used in medical practice and, most importantly, for the treatment of cancer, in particular, breast cancer ("Anastrozole", "Letrozole"). Interest in gallium compounds is associated with the discovery of a high tropicity of this element to the DNA of tumor cells, as well as cells of the reticuloendothelial system (macrophages and lymphocytes). Therefore, the synthesis of new potential drugs with gallium salts for tumor chemotherapy is an urgent task. The gallium complex of a macroheterocyclic compound of symmetrical structure based on guanazole was obtained through the formation of a three-unit product - 3,5-bis - (5 (6)-tert-butyl-3-iminoisoindoline-1-ilidenamino)-1,2,4-triazole and its complex, followed by cyclization of 3,5-diamino-1H-1,2,4-triazole in phenol. The structure of the obtained compounds was proved using modern physicochemical research methods (UV, IR, NMR spectroscopy, mass spectrometry, and elemental analysis). In the mass spectra of the obtained compounds there are peaks of molecular ions of the target products and their fragmentation products. The coincidence of the m/z values with the mass of molecular ions, as well as the characteristic distributions of molecular ions with the calculated values, confirms the composition of the synthesized gallium complexes.

Cooperative H–X Bond Activation by Electron‐Precise Aluminium and Gallium Compounds Incorporating β‐Diketiminate Ligands

The reaction pathways of the cooperative activation of protic, hydridic, and apolar H–X bonds by electron‐precise Al and Ga β‐diketiminates have been probed by means of DFT calculations. Different mechanistic scenarios have been identified and range from concerted bimolecular to associative termolecular mechanisms depending on the nature of the H–X bond. The importance of distortion in the transition‐state structure for catalyst design is emphasised.

Convenient Access to Gallium(I) Cations through Hydrogen Elimination from Cationic Gallium(III) Hydrides.

Although gallium hydrides XnGaH3-n (X = monoanionic substituent) are usually stable compounds, cationic arene-solvated species [H2Ga(arene)2]+ spontaneously eliminate dihydrogen at room temperature to afford the arene-solvated gallium(I) compounds [Ga(PhF)2][CHB11Cl11] (1) and [Ga(Ph3CH)][B(C6F5)4] (3). A key requirement appears to be the presence of a weakly coordinating anion. Use of the more basic triflimide anion, [NTf2]-, reverses the stability, i.e., the gallium(III) hydride H2GaNTf2 (4) is more stable than the gallium(I) compound GaNTf2 (5). The experimental results are supported by DFT calculations. Compounds 1 and 3 can be used as catalysts for the oligomerization of 2,4,4-trimethyl-1-pentene and the hydrosilylation of benzophenone and 1-hexene.

Synthesis and Reactivity of Tris(pentafluoroethyl)gallium Compounds

AbstractInvited for the cover of this issue is the group of Berthold Hoge from Universität Bielefeld, Germany. The cover image shows a Gallic village besieged by Roman legions, which is protected by the weakly coordinating anion [Ga(C2F5)4]– obtained from a magic potion.

Front Cover: Synthesis and Reactivity of Tris(pentafluoroethyl)gallium Compounds (Eur. J. Inorg. Chem. 30/2019)

Front Cover: Synthesis and Reactivity of Tris(pentafluoroethyl)gallium Compounds (Eur. J. Inorg. Chem. 30/2019)

Symmetrical bis-salophen probe serves as a selectively and sensitively fluorescent switch of gallium ions in living cells and zebrafish

The semi-metallic element gallium has repeatedly shown bio-activities in preclinical and clinical studies. Gallium derivatives have already entered clinical trials for treatment of various refractory malignancies. To better monitor or track the status of administered gallium compound, herein a novel fluorescent probe N,N',N'',N'''-Tetrakis(2-hydroxybenzylidene)biphenyl-3,3',4,4'-tetramine (bis-salophen) has been designed and synthesized. The bis-salophen probe was found to recognize gallium ions (Ga3+) with high selectivity and sensitivity over other cations via fluorescence “turn on” strategy. The spectroscopy results exhibited a 1:2 stoichiometry for probe and Ga3+, and the association constant and limit of detection were calculated as 8.85 × 106 M−1 and 13.0 nM, respectively. Additionally, base on spectroscopy and theoretical research, the mechanism of Ga3+ sensing action was explored by density functional theory (DFT), which indicated suppression of photoinduced electron transfer (PET) action along with the interruption of π-conjugation between salicylaldehyde and 3,3-diaminobenzidine backbone by Ga3+ ions. Furthermore, the biological applicability of bis-salophen probe were evaluated in various normal and cancer cell lines, results have shown that this probe is highly selective and sensitive for cancer cells. Finally, zebrafish imaging confirmed and indicated that the probe is also capable of examining Ga3+ ions. Collectively, these results suggest that we have successfully developed a novel probe for selective and sensitive detection of Ga3+ ions both in living cells and zebrafish. We expect that our work here will shed light on future development of Ga3+ detecting probes and wider application in the filed of biology and medicine shall be anticipated.

Synthesis and Reactivity of Tris(pentafluoroethyl)gallium Compounds

The reaction of [GaCl3(OEt2)n] with LiC2F5 surprisingly leads to the formation of the anion [Ga(C2F5)3Cl]–. The obtained lithium and tetraphenylphosphonium salts are useful starting materials for new pentafluoroethylgallium compounds. [PPh4][Ga(C2F5)3Cl] was conveniently transformed into [PPh4][Ga(C2F5)3X] (X = F, Br, I) with HF, NaBr, and NaI. Treatment of [Li(OEt2)n][Ga(C2F5)3Cl] with aqueous hydrogen chloride gives rise to the tris(pentafluoroethyl)gallane adduct [Ga(C2F5)3{(OH2)(OEt2)}]. Thermolysis of [Li(OEt2)n][Ga(C2F5)3Cl] affords another tris(pentafluoroethyl)gallane adduct, [Ga(C2F5)3(OEt2)], which can be converted into [Ga(C2F5)3(dmap)] (dmap = 4‐dimethylaminopyridine). [Ga(C2F5)3(OEt2)] as well as [Ga(C2F5)3(dmap)] react with [PPh4]Cl to [PPh4][Ga(C2F5)3Cl] and with HF to [HDMAP][Ga(C2F5)3F]. Both [Ga(C2F5)3(OEt2)] and [Ga(C2F5)3(dmap)] are precursors for the previously reported weakly coordinating anion [Ga(C2F5)4]–. Characterizations of the new compounds were carried out by NMR and IR spectroscopy, mass spectrometry, X‐ray diffraction and elemental analyses.

Interaction of Multiple Bonds with NacNacGa: Oxidative Cleavage vs Coupling and Cyclization.

The reactivity of the gallium(I) compound NacNacGa (4) to a variety of unsaturated compounds has been studied. Whereas 4 proved surprisingly unreactive toward olefins, ketones, guanidines, and thioureas, it reacts with isocyanates and carbodiimides to furnish the products of coupling of two heterocumulenes. With isothiocyanate, the C═S cleavage occurs, leading to the dimer (NacNacGa)2(μ-S)(μ-CNPh) and the cyclization product NacNacGa(S2C═NPh). These compounds were characterized by multinuclear NMR spectroscopy and X-ray crystal structure analyses. Oxidative addition of S═PPh3 occurs at elevated temperatures and results in the known dimer [NacNacGa(μ-S)]2.

Radiation Resistance of Epitaxial Structures Based on GaAs

This paper presents the results of a study on the irradiation of heterostructures based on gallium arsenide with neutrons and gamma rays. The horizontal channel of the IRT-2000 reactor with an energy of 2.65 MeV served as a source of neutrons. Two types of structures were considered: autoepitaxial (AES) and heteroepitaxial (HES). They were obtained by the MOC-hydride method under reduced pressure using gallium and aluminum organometallic compounds and arsine. The obtained results show that irradiation with neutrons and gamma-quanta just slightly changes the concentration of the charge carriers of the autoepitaxial structures and the density of the charge carriers of the heteroepitaxial structures. As for the mobility of charge carriers, some increase in their mobility is observed at the initial moment of irradiation. As the irradiation flux density increases, the mobility either stabilizes at a certain level or decreases. The increase in mobility after the first irradiation of the heterostructures indicates an increase in the lifetime of charge carriers, apparently due to a decrease in the concentration of recombination centers in the structures, most likely, the density of structural defects at the heteroboundaries. When irradiating with fast neutrons, a similar picture is observed. Initially, the mobility of charge carriers slightly increases as the concentration of charge carriers slightly changes. Then the characteristics stabilize. An increase in the uniformity of properties over the area of the structures is observed. It is assumed that this is due to the appearance of clusters of defects and impurities.

Selective Recovery of Gallium (Indium) from Metal Organic Chemical Vapor Deposition Dust—A Sustainable Process

Gallium (indium)-containing dust as a hazardous waste generated from light-emitting diode (LED) epitaxial wafer manufacturing attracts worldwide attention because of both resources and environmental importance. Oxidative roasting combined with acidic leaching is frequently utilized to recover the corresponding metals from such dust, while the recovery rate is usually low because of the rather inert physicochemical properties of gallium compounds. Simultaneously, the selectivity of leaching is low, which results in complex separation or purification is required in order to obtain the required product (e.g., metallic gallium, Ga(OH)3). In this research, it is demonstrated that the selectivity of leaching can be achieved via properly controlling the physicochemical properties of the leaching solution and the leaching conditions. The leaching rate of gallium can reach 90.01% through optimizing the effects of different parameters, including leaching reagent concentration, solid-to-liquid ratio, reaction temper...

Iron/Heme Metabolism-Targeted Gallium(III) Nanoparticles Are Active against Extracellular and Intracellular Pseudomonas aeruginosa and Acinetobacter baumannii.

Iron/heme acquisition systems are critical for microorganisms to acquire iron from the human host, where iron sources are limited due to the nutritional immune system and insolubility of the ferric form of iron. Prior work has shown that a variety of gallium compounds can interfere with bacterial iron acquisition. This study explored the intra- and extracellular antimicrobial activities of gallium protoporphyrin (GaPP), gallium mesoporphyrin (GaMP), and nanoparticles encapsulating GaPP or GaMP against the Gram-negative pathogens Pseudomonas aeruginosa and Acinetobacter baumannii, including clinical isolates. All P. aeruginosa and A. baumannii isolates were susceptible to GaPP and GaMP, with MICs ranging from 0.5 to ∼32 μg/ml in iron-depleted medium. Significant intra- and extracellular growth inhibition was observed against P. aeruginosa cultured in macrophages at a gallium concentration of 3.3 μg/ml (5 μM) of all Ga(III) compounds, including nanoparticles. Nanoparticle formulations showed prolonged activity against both P. aeruginosa and A. baumannii in previously infected macrophages. When the macrophages were loaded with the nanoparticles 3 days prior to infection, there was a 5-fold decrease in growth of P. aeruginosa in the presence of single emulsion F127 copolymer nanoparticles encapsulating GaMP (eFGaMP). In addition, all Ga(III) porphyrins and nanoparticles showed significant intracellular and antibiofilm activity against both pathogens, with the nanoparticles exhibiting intracellular activity for 3 days. Ga nanoparticles also increased the survival rate of Caenorhabditis elegans nematodes infected by P. aeruginosa and A. baumannii Our results demonstrate that Ga nanoparticles have prolonged in vitro and in vivo activities against both P. aeruginosa and A. baumannii, including disruption of their biofilms.

Intense Pulsed Light Annealing Process of Indium-Gallium-Zinc-Oxide Semiconductors via Flash White Light Combined with Deep-UV and Near-Infrared Drying for High-Performance Thin-Film Transistors.

In this study, an intense pulsed light (IPL) process for annealing an indium-gallium-zinc-oxide (IGZO) semiconductor was conducted via flash white light combined with near-infrared (NIR) and deep-ultraviolet (DUV) drying to form a thin-film transistor (TFT). The IGZO thin-film semiconductor was fabricated using a solution-based process on a doped-silicon wafer covered with silicon dioxide. In order to optimize the IPL irradiation condition for the annealing process, the flash white light irradiation energy was varied from 70 to 130 J/cm2. Drying by NIR and DUV irradiation was employed and optimized to improve the performance of the TFT during IPL annealing. A TFT with a bottom-gate and top-contact structure was formed by depositing an aluminum electrode on the source and drain on the IPL-annealed IGZO. The electrical transfer characteristic of the TFT was measured using a parameter analyzer. The field effect mobility of the saturation regime and on/off current ratio were evaluated. Changes of the metal-oxide bonds in the IGZO thin film were analyzed using X-ray photoelectron spectroscopy to verify the effect of NIR and DUV drying and IPL annealing. Also, the distributions of the carrier concentration on the IPL-annealed IGZO were measured through a hall-effect system to deeply investigate the transition of the electrical characteristic of the TFT. From the results, it was found that the bond between oxygen and the gallium compound was activated via DUV irradiation. The NIR- and DUV-assisted IPL-annealed IGZO-based TFT showed highly enhanced electrical performance with a 7.7 cm2/V·s mobility and a 3 × 106 on/off ratio.

Aqueous Solution Processing of Combustible Precursor Compounds into Amorphous Indium Gallium Zinc Oxide (IGZO) Semiconductors for Thin Film Transistor Applications.

Combustion synthesis of semiconducting amorphous indium gallium zinc oxide IGZO (In:Ga:Zn, 7:1:1.5) thin films was carried out using urea nitrate precursor compounds of indium(III), gallium(III) and zinc(II). This approach provides further understanding towards the oxide formation process under a moderate temperature regime by employment of well-defined coordination compounds. All precursor compounds were fully characterized by spectroscopic techniques as well as by single crystal structure analysis. Their intrinsic thermal decomposition was studied by a combination of differential scanning calorimetry (DSC) and thermogravimetry coupled with mass spectrometry and infrared spectroscopy (TG-MS/IR). For all precursors a multistep decomposition involving a complex redox-reaction pathway under in situ formation of nitrogen containing molecular species was observed. Controlled thermal conversion of a mixture of the indium, gallium and zinc urea nitrate complexes into ternary amorphous IGZO films could thus be achieved. Thin film transistors (TFTs) were fabricated from a defined compositional mixture of the molecular precursors. The TFT devices exhibited decent charge carrier mobilities of 0.4 and 3.1 cm2 /(Vs) after annealing of the deposited films at temperatures as low as 250 and 350 °C, respectively. This approach represents a significant step further towards a low temperature solution processing of semiconducting thin films.

Antimicrobial Activity of Gallium Compounds on ESKAPE Pathogens.

ESKAPE bacteria are a major cause of multidrug-resistant infections, and new drugs are urgently needed to combat these pathogens. Given the importance of iron in bacterial physiology and pathogenicity, iron uptake and metabolism have become attractive targets for the development of new antibacterial drugs. In this scenario, the FDA-approved iron mimetic metal Gallium [Ga(III)] has been successfully repurposed as an antimicrobial drug. Ga(III) disrupts ferric iron-dependent metabolic pathways, thereby inhibiting microbial growth. This work provides the first comparative assessment of the antibacterial activity of Ga(NO3)3 (GaN), Ga(III)-maltolate (GaM), and Ga(III)-protoporphyrin IX (GaPPIX), belonging to the first-, second- and third-generation of Ga(III) formulations, respectively, on ESKAPE species, including reference strains and multidrug-resistant (MDR) clinical isolates. In addition to the standard culture medium Mueller Hinton broth (MHB), iron-depleted MHB (DMHB) and RPMI-1640 supplemented with 10% human serum (HS) (RPMI-HS) were also included in Ga(III)-susceptibility tests, because of their different nutrient and iron contents. All ESKAPE species were resistant to all Ga(III) compounds in MHB and DMHB (MIC > 32 μM), except Staphylococcus aureus and Acinetobacter baumannii, which were susceptible to GaPPIX. Conversely, the antibacterial activity of GaN and GaM was very evident in RPMI-HS, in which the low iron content and the presence of HS better mimic the in vivo environment. In RPMI-HS about 50% of the strains were sensitive (MIC < 32) to GaN and GaM, both compounds showing a similar spectrum of activity, although GaM was more effective than GaN. In contrast, GaPPIX lost its antibacterial activity in RPMI-HS likely due to the presence of albumin, which binds GaPPIX and counteracts its inhibitory effect. We also demonstrated that the presence of multiple heme-uptake systems strongly influences GaPPIX susceptibility in A. baumannii. Interestingly, GaN and GaM showed only a bacteriostatic effect, whereas GaPPIX exerted a bactericidal activity on susceptible strains. Altogether, our findings raise hope for the future development of Ga(III)-based compounds in the treatment of infections caused by multidrug-resistant ESKAPE pathogens.

Structure, magnetic and cryogenic magneto-caloric properties in intermetallic gallium compounds RE2Co2Ga (RE = Dy, Ho, Er, and Tm)

The intermetallic gallium compounds RE2Co2Ga with different rare earths (RE = Dy, Ho, Er, and Tm) were synthesized, and their crystal structure, microstructure, magnetic, and cryogenic magneto-caloric performances were investigated. The RE2Co2Ga compounds crystallize with an ordered orthorhombic W2B2Co-type structure (space group Immm). All the RE2Co2Ga compounds undergo ferromagnetic (FM) ordering (second-order) from a paramagnetic to FM transition which induces reversible magneto-caloric effects (MCE). The Curie temperatures (TC) in RE2Co2Ga compounds are determined to be 55.0, 38.5, 25.5, and 11.6 K for RE = Dy, Ho, Er, and Tm, respectively, which fulfill the de Gennes scaling. The RE2Co2Ga compounds show relatively small MCE (i.e., −ΔSM, isothermal magnetic entropy change) around their own phase transition temperatures, and the maximal values of −ΔSM are 7.5, 14.6, 11.2, and 13.2 J/kg K in the field change (ΔH) of 7 T for RE = Dy, Ho, Er, and Tm, respectively. Accordingly, the values of the relative cooling power are 212, 335, 304, and 239 J/kg, respectively.

Synthesis of N→Ga Coordinated Gallium(II)–Gallium(II) Compounds

Synthesis of the N→Ga coordinated gallium(II)–gallium(II) compounds containing the N,C,N‐chelating ligand L [L: {2,6‐(Me2NCH2)2C6H3}–] is reported. Attempts to stabilize the subvalent digallene [LGa]2 by reduction of [L(Cl)Ga]2 (1) or by hydrogen elimination from [L(H)Ga]2 (2) failed, but an unexpected complex, [L(C6H5CH2)Ga]2 (3), was isolated. It is possibly the product of the reaction of the parent digallene [LGa]2 with toluene.

An investigation about the luminescence mechanism of SrGa2O4:Eu3+ showing no detectable energy transfer from the host to the dopant ions

Un-doped SrGa2O4 and a series of Eu3+ ions doped SrGa2O4 were synthesized by conventional solid state reactions. The X-ray diffraction patterns, photoluminescence excitation and photoluminescence spectra, diffuse reflection spectra of these samples were recorded and analyzed. Un-doped SrGa2O4 can emit blue-violet light in a broad band peaking at 407 nm under the excitation at 234 and 252 nm. Eu3+ ions doped SrGa2O4 phosphors exhibit red emission under the excitation at 274 nm. However, there is no detectable energy transfer from the host to doped Eu3+ ions. The further luminescence mechanism and reasons for the absence of energy transfer from the host to doped Eu3+ ions are discussed in detail. A novel mechanism about the luminescence of gallium compounds is proposed based on our experimental results. An energy level diagram is proposed to illustrate the luminescence mechanism of gallium compounds and reasons for the absence of energy transfer from the host to doped Eu3+ ions.

Gallium Maltolate Disrupts Tumor Iron Metabolism and Retards the Growth of Glioblastoma by Inhibiting Mitochondrial Function and Ribonucleotide Reductase.

Gallium, a metal with antineoplastic activity, binds transferrin (Tf) and enters tumor cells via Tf receptor1 (TfR1); it disrupts iron homeostasis leading to cell death. We hypothesized that TfR1 on brain microvascular endothelial cells (BMEC) would facilitate Tf-Ga transport into the brain enabling it to target TfR-bearing glioblastoma. We show that U-87 MG and D54 glioblastoma cell lines and multiple glioblastoma stem cell (GSC) lines express TfRs, and that their growth is inhibited by gallium maltolate (GaM) in vitro After 24 hours of incubation with GaM, cells displayed a loss of mitochondrial reserve capacity followed by a dose-dependent decrease in oxygen consumption and a decrease in the activity of the iron-dependent M2 subunit of ribonucleotide reductase (RRM2). IHC staining of rat and human tumor-bearing brains showed that glioblastoma, but not normal glial cells, expressed TfR1 and RRM2, and that glioblastoma expressed greater levels of H- and L-ferritin than normal brain. In an orthotopic U-87 MG glioblastoma xenograft rat model, GaM retarded the growth of brain tumors relative to untreated control (P = 0.0159) and reduced tumor mitotic figures (P = 0.045). Tumors in GaM-treated animals displayed an upregulation of TfR1 expression relative to control animals, thus indicating that gallium produced tumor iron deprivation. GaM also inhibited iron uptake and upregulated TfR1 expression in U-87 MG and D54 cells in vitro We conclude that GaM enters the brain via TfR1 on BMECs and targets iron metabolism in glioblastoma in vivo, thus inhibiting tumor growth. Further development of novel gallium compounds for brain tumor treatment is warranted. Mol Cancer Ther; 17(6); 1240-50. ©2018 AACR.

Gallium Complexes as Anticancer Drugs.

Clinical trials have shown gallium nitrate, a group 13 (formerly IIIa) metal salt, to have antineoplastic activity against non-Hodgkin's lymphoma and urothelial cancers. Interest in gallium as a metal with anticancer properties emerged when it was discovered that 67Ga(III) citrate injected in tumor-bearing animals localized to sites of tumor. Animal studies showed non-radioactive gallium nitrate to inhibit the growth of implanted solid tumors. Following further evaluation of its efficacy and toxicity in animals, gallium nitrate, Ga(NO3)3, was designated an investigational drug by the National Cancer Institute (USA) and advanced to Phase 1 and 2 clinical trials. Gallium(III) shares certain chemical characteristics with iron(III) which enable it to interact with iron-binding proteins and disrupt iron-dependent tumor cell growth. Gallium's mechanisms of action include the inhibition of cellular iron uptake and disruption of intracellular iron homeostasis, these effects result in inhibition of ribonucleotide reductase and mitochondrial function, and changes in the expression in proteins of iron transport and storage. Whereas the growth-inhibitory effects of gallium become apparent after 24 to 48 hours of incubation of cells, an increase in intracellular reactive oxygen species (ROS) is seen with 1 to 4 hours of incubation. Gallium-induced ROS consequently triggers the upregulation of metallothionein and hemoxygenase-1 genes. Beyond the first generation of gallium salts such as gallium nitrate and gallium chloride, a new generation of gallium-ligand complexes such as tris(8-quinolinolato)gallium(III) (KP46) and gallium maltolate has emerged. These agents are being evaluated in the clinic while other ligands for gallium are in preclinical development. These newer agents appear to possess greater antitumor efficacy and a broader spectrum of antineoplastic activity than the earlier generation of gallium compounds.

Catalytic Reduction of Carbon Dioxide Using Cationic Organoaluminum and -Gallium Compounds

Ethide abstraction from Et3M (M = Al and Ga), (2,6-Ph2C6H3)AlEt2, 1, and (2,6-Dipp2C6H3)GaEt2, 2 (Dipp = 2,6-iPr2C6H3), using the silylium ion [Et3Si][CHB11Cl11] afforded crystalline ion-like compounds [Et2M][CHB11Cl11] (M = Al, 3; Ga, 5) and [(2,6-Ph2C6H3)AlEt][CHB11Cl11], 4, and the likely solvent-separated ion pair [(2,6-Dipp2C6H3)GaEt][CHB11Cl11], 6. Crystalline compounds 3–5 feature cation···anion contacts in the solid state, and their solubility in low polarity benzene indicates that these contacts are maintained in solution. All compounds catalyze the reduction of CO2 with Et3SiH, but the activity of the gallium compound 5 is significantly lower due to its polymeric structure and the lower Lewis acidity of gallium. Whereas the reduction products from the reactions catalyzed by compounds 3–5 are mostly methane and toluene (from Friedel–Crafts alkylation of the benzene solvent), catalysis by 6 led mostly to Et3SiOCH3.