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Purpose: This study aimed to examine the prognostic impact of concomitant pH-regulating drug use in patients with epidermal growth factor receptor (EGFR)-mutation-positive non-small-cell lung cancer (NSCLC) receiving EGFR-tyrosine kinase inhibitors (TKIs)., Methods: We conducted a nationwide retrospective cohort study and reviewed clinical data of consecutive patients with NSCLC treated with the first-line EGFR-TKIs in 46 hospitals between April 2010 and March 2020. Cox regression analyses were conducted to examine the differences in overall survival (OS) between patients treated with and without concomitant pH-regulating drugs, including potassium-competitive acid blockers (P-CABs), proton pump inhibitors (PPIs), and H 2 -receptor antagonists (H 2 RAs)., Results: A total of 758 patients were included in the final dataset, of which 307 (40%) were administered concomitant pH-regulating drugs while receiving frontline EGFR-TKIs. After adjusting for basic patient characteristics, patients administered gefitinib, erlotinib, afatinib, and osimertinib with concomitant pH-regulating drugs had lower OS than those without concomitant pH-regulating drugs, with hazard ratios of 1.74 (with a 95% confidence interval of 1.34-2.27), 1.33 (0.80-2.22), 1.73 (0.89-3.36), and 5.04 (1.38-18.44), respectively. The 2-year OS rates of patients receiving gefitinib with or without concomitant pH-regulating drugs were 65.4 and 77.5%, those for erlotinib were 55.8 and 66.6%, and those for afatinib were 63.2 and 76.9%, respectively. The 1-year OS rates of patients receiving osimertinib with or without concomitant pH-regulating drugs were 88.1% and 96.9%, respectively., Conclusion: In addition to the first-generation EGFR-TKIs, the second- and third-generation EGFR-TKIs also resulted in OS deterioration in patients with EGFR mutation-positive NSCLC when used concurrently with pH-regulating drugs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Herein, we disclose the Ni-catalyzed ring-opening C-O functionalization of peri -xanthenoxanthenes using Grignard reagents that forms 8-monofunctionalized binaphthols. 1,2-Bis(dicyclohexylphosphino)ethane was the best ligand for alkylations and ICy for arylation. After mechanistic investigations, we assumed that the reaction proceeds via C-O reduction and subsequent C-O functionalization. To verify the mechanism, the intermediate after reduction was isolated. Moreover, the asymmetric addition, using 8-octylbinaphthol after optical resolution, was studied.

The ability of α-borylated naphthalene-based aromatic compounds is important because it provides ready access to interesting novel extended π-systems. In this report, we disclose the Ni-catalyzed α-selective C-H borylations of naphthalene-based aromatic compounds. The reaction proceeds with peri -xanthenoxanthene and other aromatic compounds to regioselectively afford the α-borylated products without directing groups. The selectivities of these transformations are different from those of Ir-catalyzed C-H borylation reactions and can be used in a complementary manner.

C-H trifluoromethanesulfonyloxylation (triflation) of 1,1'-bi-2-naphthol (BINOL) derivatives has been established under mild conditions using 1,3-diiodo-5,5-dimethylhydantoin (DIH) and trifluoromethanesulfonic acid (TfOH). Up to eight TfO groups can be introduced in a single operation. The resulting highly oxidized BINOL derivatives can be successfully converted to 8,8'-dihydroxy BINOL and bisnaphthoquinone compounds. Mechanistic studies suggested that C-H triflation occurs in the form of an aromatic substitution reaction via the in situ formation of a radical cation.

Cu-catalyzed C-H/C-O cyclization of 2,2'-binaphthol, using air as an oxidant, was developed. C-H functionalization of binaphthols occurred at the 8,8'-position to form peri-xanthenoxanthenes that exhibit high charge-carrier mobility. The reaction can tolerate a wide variety of functional groups and afforded the corresponding peri-xanthenoxanthene derivatives via an efficient procedure.

Multifunctional catalysts are of great interest in catalysis because their multiple types of catalytic or functional groups can cooperatively promote catalytic transformations better than their constituents do individually. Herein we report a new synthetic route involving the surface functionalization of nanoporous silica with a rationally designed and synthesized dihydrosilane (3-aminopropylmethylsilane) that leads to the introduction of catalytically active grafted organoamine as well as single metal atoms and ultrasmall Pd or Ag-doped Pd nanoparticles via on-site reduction of metal ions. The resulting nanomaterials serve as highly effective bifunctional dehydrogenative catalysts for generation of H 2 from formic acid.

Polymethylhydrosiloxane has been grafted on the surface of a hierarchically porous silica monolith using a facile catalytic reaction between Si-H and silanol to anchor the polymer. This easy methodology leads to the functionalization of the surface of a silica monolith, where a large amount of free Si-H bonds remain available for reducing metal ions in solution. Palladium nanoparticles of 15 nm have been synthesized homogeneously inside the mesopores of the monolith without any stabilizers, using a flow of a solution containing Pd 2+ . This monolith was used as column-type fixed bed catalyst for continuous flow hydrogenation of styrene and selective hydrogenation of 3-hexyn-1-ol, in each case without a significant decrease of the catalytic activity after several hours or days. Conversion, selectivity, and stereoselectivity of the alkyne hydrogenation can be tuned by flow rates of hydrogen and the substrate solution, leading to high productivity (1.57 mol g(Pd) -1 h -1 ) of the corresponding cis-alkene.

Inspired by homogeneous borane catalysts that promote Si-H bond activation, we herein describe an innovative method for surface modification of silica using hydrosilanes as the modification precursor and tris(pentafluorophenyl)borane (B(C6F5)3) as the catalyst. Since the surface modification reaction between surface silanol and hydrosilane is dehydrogenative, progress and termination of the reaction can easily be confirmed by the naked eye. This new metal-free process can be performed at room temperature and requires less than 5 min to complete. Hydrosilanes bearing a range of functional groups, including alcohols and carboxylic acids, have been immobilized by this method. An excellent preservation of delicate functional groups, which are otherwise decomposed in other methods, makes this methodology appealing for versatile applications.

Synthesis of class II hybrid silica materials requires the formation of covalent linkage between organic moieties and inorganic frameworks. The requirement that organosilylating agents be present to provide the organic part limits the synthesis of functional inorganic oxides, however, due to the water sensitivity and challenges concerning purification of the silylating agents. Synthesis of hybrid materials with stable molecules such as simple alcohols, rather than with these difficult silylating agents, may therefore provide a path to unprecedented functionality. Herein, we report the novel functionalization of silica with organic alcohols for the first time. Instead of using hydrolyzable organosilylating agents, we used stable organic alcohols with a Zn(II) catalyst to modify the surface of a recently discovered highly reactive macro-mesoporous hydrogen silsesquioxane (HSQ, HSiO1.5) monolith, which was then treated with water with the catalyst to form surface-functionalized silica. These materials were comprehensively characterized with FT-IR, Raman, solid-state NMR, fluorescence spectroscopy, thermal analysis, elemental analysis, scanning electron microscopy, and nitrogen adsorption-desorption measurements. The results obtained from these measurements reveal facile immobilization of organic moieties by dehydrogenative addition onto surface silane (Si-H) at room temperature with high loading and good tolerance of functional groups. The organic moieties can also be retrieved from the monoliths for recycling and reuse, which enables cost-effective and ecological use of the introduced catalytic/reactive surface functionality. Preservation of the reactivity of as-immobilized organic alcohols has been confirmed, moreover, by successfully performing copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reactions on the immobilized silica surfaces.

Enhanced fluorescence detection of metal ions was realized in a system consisting of a fluorescent 2,2'-bipyridine (BPy) receptor and light-harvesting periodic mesoporous organosilica (PMO). The fluorescent BPy receptor with two silyl groups was synthesized and covalently attached to the pore walls of biphenyl (Bp)-bridged PMO powder. The fluorescence intensity from the BPy receptor was significantly enhanced by the light-harvesting property of Bp-PMO, that is, the energy funneling into the BPy receptor from a large number of Bp groups in the PMO framework which absorbed UV light effectively. The enhanced emission of the BPy receptor was quenched upon the addition of a low concentration of Cu(2+) (0.15-1.2×10(-6)  M), resulting in the sensitive detection of Cu(2+). Upon titration of Zn(2+) (0.3-6.0×10(-6)  M), the fluorescence excitation spectrum was systematically changed with an isosbestic point at 375 nm through 1:1 complexation of BPy and Zn(2+) similar to that observed in BPy-based solutions, indicating almost complete preservation of the binding property of the BPy receptor despite covalent fixing on the solid surface. These results demonstrate that light-harvesting PMOs have great potential as supporting materials for enhanced fluorescence chemosensors., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel spirobifluorene-bridged allylsilane precursor, which can be easily purified by silica gel chromatography, was prepared by using a new molecular building block for allylsilane sol-gel precursors (MBAS) and successfully converted into a highly fluorescent periodic mesoporous organosilica film., (© The Royal Society of Chemistry 2011)

Polycondensation of 9-mesityl-10-methylacridinium-bridged organosilane in the presence of a nonionic surfactant yielded a mesostructured organosilica solid with a functional framework that exhibited long-lived photoinduced charge separation.

Molecular orbital theory calculations were carried out to predict the occurrence of Si-C bond cleavage in various organosilane precursors during polycondensation to organosilica hybrids under acidic and basic conditions. On the basis of proposed mechanisms for cleavage of the Si-C bonds, the proton affinity (PA) of the carbon atom at the ipso-position and the PA of the carbanion generated after Si-C cleavage were chosen as indices for Si-C bond stability under acidic and basic conditions, respectively. The indices were calculated using a density functional theory (DFT) method for model compounds of organosilane precursors (R-Si(OH)(3)) having organic groups (R) of benzene (Ph), biphenyl (Bp), terphenyl (Tph), naphthalene (Nph), N-methylcarbazole (MCz), and anthracene (Ant). The orders for the predicted stability of the Si-C bond were Ph > Nph > Bp > Ant > Tph > MCz for acidic conditions and Ph > MCz > Bp > Nph > Tph > Ant for basic conditions. These behaviors were primarily in agreement with experimental results where cleavage of the Si-C bonds occurred for Tph (both acidic and basic), MCz (acidic), and Ant (basic). The Si-C bond cleavage of organosilane precursors during polycondensation is qualitatively predicted from these indices based on our theoretical approach.

Highly ordered periodic mesoporous organosilica synthesized from a newly designed 9(10H)-acridone bridged organosilane precursor exhibited efficient light-harvesting antenna properties for visible light, at wavelengths up to 450 nm.

We report that 2,6-naphthylene-bridged periodic mesoporous organosilicas exhibit unique fluorescence behavior that reflects molecular-scale periodicities in the framework. Periodic mesoporous organosilicas consisting of naphthalene-silica hybrid frameworks were synthesized by hydrolysis and condensation of a naphthalene-derived organosilane precursor in the presence of a template surfactant. The morphologies and meso- and molecular-scale periodicities of the organosilica materials strongly depend on the synthetic conditions. The naphthalene moieties embedded within the molecularly ordered framework exhibited a monomer-band emission, whereas those embedded within the amorphous framework showed a broad emission attributed to an excimer band. These results suggest that the naphthalene moieties fixed within the crystal-like framework are isolated in spite of their densely packed structure, different from conventional organosilica frameworks in which only excimer emission was observed for both the crystal-like and amorphous frameworks at room temperature. This key finding suggests a potential to control interactions between organic groups and thus the optical properties of inorganic/organic hybrids.

Organosilica porous solids containing chiral organic moieties in the framework with an enantiomeric purity of 95% ee, estimated by eluting organic constituent units from chiral organosilicas, were synthesized from a newly designed chiral (R)-(+)-1,2-bis(trimethoxysilyl)phenylethane precursor via a surfactant-mediated self-assembly approach.

A rhodium-catalyzed asymmetric isomerization of racemic alpha-arylpropargyl alcohols to beta-chiral indanones has been developed. High enantioselectivity has been realized by the use of a newly developed axially chiral bisphosphine ligand. This ligand is unique in the sense that its axial chirality is fixed to a single configuration upon complexation to a transition metal due to other chiral axes existing within the same molecule.

[reaction: see text] Bis(pyridine)iodonium tetrafluoroborate was successfully used for regioselective iodination of BINAP dioxide to give 5,5'-diiodoBINAP dioxide in an excellent yield of 92%, with no observed formation of 4,4'-diiodoBINAP dioxide. A Sonogashira cross-coupling reaction with 5,5'-diiodoBINAP dioxide gave the desired bis(trimethylsilylethynyl) product in 86% yield. The resulting 5,5'-disubstituted BINAP dioxides were reduced to the corresponding phosphines, which were used as chiral ligands for rhodium-catalyzed asymmetric 1,4-addition of phenylboronic acid to 2-cyclohexenone to give 3-phenylcyclohexanone in excellent yield with high enantioselectivity.

The bridged allylorganosilanes 1,4-bis(diallylethoxysilyl)benzene and 1,4-bis(triallylsilyl)benzene are presented as new precursors for the surfactant-assisted synthesis of ordered mesoporous organosilica with pore walls having crystal-like molecular-scale periodicity. This approach provides a new route to the formation of periodic mesostructures with crystal-like pore walls. The synthesis method presented is applicable to the preparation of mesoporous organosilica with bulky organic groups, the precursors of which are typically impossible to obtain in high purity.

Catalytic asymmetric Grignard cross-coupling of 1,9-disubstituted dibenzothiophenes (6a-c) and dinaphthothiophene (6d) with aryl- and alkyl-Grignard reagents (7) proceeded with high enantioselectivity (up to 95% ee) in the presence of a nickel catalyst (3-6 mol %) coordinated with 2-diphenylphosphino-1,1'-binaphthyl (H-MOP) or oxazoline-phosphine ligand (i-Pr-phox) in THF to give 2-mercapto-2'-substituted-1,1'-biphenyls (8a-c) and 2-mercapto-2'-substituted-1,1'-binaphthyls (8d) in high yields. The mercapto group in the axially chiral cross-coupling products was converted into several functional groups by way of the methylsulfinyl group. The rate of flipping in dinaphthothiophene was measured by variable-temperature (31)P NMR analysis of methylphenylphosphinyldinaphthothiophene derivative (21).

New axially chiral 2,2'-bipyridine N,N'-dioxides 1 were obtained in an enantiomerically pure form by way of cyclic diesters 6 or 7 which were formed by the esterification of diols 2 with (R)-2,2'-bis(chlorocarbonyl)-1,1'-binaphthalene (5). Epimerization of the kinetic products at the ester formation (R(nap),S(pyr))-6 to the thermodynamically stable isomers (R(nap),R(pyr))-7 was observed in refluxing toluene or in the presence of trifluoroacetic acid. One of the N,N'-dioxides 1a which is substituted with phenyl groups at the 6 and 6' positions was found to be highly catalytically active and enantioselective for the asymmetric allylation of aldehydes with allyl(trichloro)silane giving homoallyl alcohols.

Treatment of an (allyl)organosilane with silica gel in refluxing toluene brought about deallylation forming an Si-O-Si bond with the silicon on the silica gel. This Si-O-Si bond formation provides us with a new reliable method for the functionalization of a silica gel surface.

Asymmetric cross-coupling of dinaphtho[2,1-b:1',2'-d]thiophene with ArMgBr (Ar = Ph, 4-MeC6H4, 4-MeOC6H4) proceeded with high enantioselectivity in THF at 20 degrees C in the presence of 3 mol % of a nickel catalyst generated from Ni(cod)2 and a chiral oxazoline-phosphine ligand to give high yields of axially chiral 2-mercapto-2'-aryl-1,1'-binaphthyls, whose enantiomeric excesses are over 93%. The mercapto group in the chiral binaphthyl was converted into iodo, boryl, and phosphino groups without racemization.

[reaction: see text] New axially chiral 2,2'-bipyridine N,N'-dioxides were obtained by a new method that does not involve any procedures for the separation of enantiomers. One of the dioxides, (R)-3,3'-bis(hydroxymethyl)-6,6'-diphenyl-2,2'-bipyridine N,N'-dioxide, exhibited extremely high catalytic activity for the asymmetric allylation of aldehydes with allyl(trichloro)silane. The allylation of aromatic aldehydes proceeded in the presence of 0.01 or 0.1 mol % of the dioxide catalyst to give the corresponding homoallyl alcohols of up to 98% ee.

Double hydrosilylation of arylacetylenes with trichlorosilane catalyzed first by platinum and second by a chiral monophosphine-palladium complex generated the corresponding 1,2-bis(silyl)-1-arylethanes, the oxidation of which with hydrogen peroxide gave 1-aryl-1,2-diols of high enantiomeric purity (94-98% ee) in high yields.