Near-infrared and metal-free tetra(butylamino)phthalocyanine nanoparticles for dual modal cancer phototherapy

Synergistic phototherapy combining photodynamic therapy (PDT) and photothermal therapy (PTT) based on near-infrared (NIR) dyes using a single light source offers the opportunity to treat diseases at deep locations. In this study, we reported human serum albumin (HSA)-involving tetra(butylamino)phthalocyanine (Pc)-based nanomaterials of HSA-α-Pc and HSA-β-Pc as highly efficient dual-phototherapy agents, namely 1(4),8(11),15(18),22(25)-tetra(butylamino)phthalocyanine (α-Pc) and 2(3),9(10),16(17),23(24)-tetra(butylamino)phthalocyanine (β-Pc). Both HSA-α-Pc and HSA-β-Pc showed excellent photothermal effects under a single NIR (808 nm) laser irradiation due to the S₁ fluorescence emission quenching of Pcs. Compared to HSA-β-Pc, HSA-α-Pc exhibited better singlet oxygen generation ability and its highly efficient PDT/PTT dual-phototherapy was also well evidenced via in vitro and vivo experiments under a single 808 nm laser irradiation. Overall, this approach would be viable for the fabrication of more new Pc-based metal-free nano agents for PDT/PTT synergistic phototherapy upon a single NIR light source.

Two new HSA-involved tetra(butylamino)phthalocyanine composite nanoparticles, as highly efficient dual-phototherapy agents upon a single NIR laser irradiation, were reported.     

Revealing the in situ NaF generation balance for user-friendly controlled synthesis of sub-10 nm monodisperse low-level Gd3+-doped β-NaYbF4:Er

Herein, user-friendly control of the synthesis of sub-10 nm hexagonal (β-) NaYbF₄:Er nanocrystals (NCs) with extremely low-level Gd³⁺ doping (0%, 10 mol%) was achieved. We reveal for the first time that the effective sodium/fluoride levels during the formation of cubic (α-) nuclei are not only controlled by the sodium/fluoride to rare-earth precursor ratios used, but also sensitively restricted by the in situ NaF generation reaction in a sodium oleate-based solvothermal system. Excessive in situ NaF generation will lead to a respective sodium- and fluoride-deficient environment, delayed α-to-β transition and larger β-NCs. Based on these effects, sub-10 nm monodisperse low-level Gd³⁺-doped β-NaYbF₄:Er was obtained with a user-friendly low fluoride dosage by finely balancing this NaF generation reaction and achieving an intrinsic optimized sodium-fluoride level for NC nucleation. Notably, our work represents the first example where the focus is on the competing in situ NaF generation reaction and its use for nucleation regulation, as well as for the user-friendly control of the solvothermal synthesis of sub-10 nm β-NaYbF₄:Er.

User-friendly solvothermal controlled synthesis of sub-10 nm monodisperse low-level Gd³⁺-doped β-NaYbF₄:Er was achieved via revealing and balancing the competing in situ NaF generation reaction.     

Chemodivergent synthesis of N-(pyridin-2-yl)amides and 3-bromoimidazo[1,2-a]pyridines from α-bromoketones and 2-aminopyridines

N-(Pyridin-2-yl)amides and 3-bromoimidazo[1,2-a]pyridines were synthesized respectively from α-bromoketones and 2-aminopyridine under different reaction conditions. N-(Pyridin-2-yl)amides were formed in toluene via C–C bond cleavage promoted by I₂ and TBHP and the reaction conditions were mild and metal-free. Whereas 3-bromoimidazopyridines were obtained in ethyl acetate via one-pot tandem cyclization/bromination when only TBHP was added, the cyclization to form imidazopyridines was promoted by the further bromination, no base was needed, and the versatile 3-bromoimidazopyridines could be further transferred to other skeletons.

N-(Pyridin-2-yl)amides and 3-bromoimidazo[1,2-a]pyridines were synthesized respectively from α-bromoketones and 2-aminopyridine under different reaction conditions.     

An efficient access to β-ketosulfones via β-sulfonylvinylamines: metal–organic framework catalysis for the direct C–S coupling of sodium sulfinates with oxime acetates

A copper-based framework Cu₂(OBA)₂(BPY) was synthesized and used as a recyclable heterogeneous catalyst for the synthesis of β-sulfonylvinylamines from sodium sulfinates and oxime acetates via direct C–S coupling reaction. The transformation was remarkably affected by the solvent, and chlorobenzene emerged as the best option. This Cu-MOF displayed higher activity than numerous conventional homogeneous and MOF-based catalysts. The catalyst was reutilized many times in the synthesis of β-sulfonylvinylamines without considerably deteriorating in catalytic efficiency. These β-sulfonylvinylamines were readily converted to the corresponding β-ketosulfones via a hydrolysis step with aqueous HCl solution. To the best of our knowledge, this direct C–S coupling reaction to achieve β-sulfonylvinylamines was not previously conducted with a heterogeneous catalyst.

Cu₂(OBA)₂(BPY) was used as catalyst for the synthesis of β-sulfonylvinylamines from sodium sulfinates and oxime acetates. These β-sulfonylvinylamines were readily converted to corresponding β-ketosulfones via a hydrolysis step.     

The synthesis of imidazo[1,5-a]quinolines via a decarboxylative cyclization under metal-free conditions

An iodine-mediated decarboxylative cyclization was developed from α-amino acids and 2-methyl quinolines under metal-free conditions, affording a variety of imidazo[1,5-a]quinolines with moderate to good yields.

An iodine-mediated decarboxylative cyclization was developed from α-amino acids and 2-methyl quinolines under metal-free conditions, affording a variety of imidazo[1,5-a]quinolines with moderate to good yields.     

Cationic palladium(ii)-catalyzed synthesis of substituted pyridines from α,β-unsaturated oxime ethers

An efficient method for the synthesis of multi-substituted pyridines from β-aryl-substituted α,β-unsaturated oxime ethers and alkenes via Pd-catalyzed C–H activation has been developed. The method, using Pd(OAc)₂ and a sterically hindered pyridine ligand, provides access to various multi-substituted pyridines with complete regioselectivity. Mechanistic studies suggest that the pyridine products are formed by Pd-catalyzed electrophilic C–H alkenylation of α,β-unsaturated oxime followed by aza-6π-electrocyclization. The utility of this method is showcased by the synthesis of 4-aryl-substituted pyridine derivatives, which are difficult to synthesize efficiently using previously reported Rh-catalyzed strategies with alkenes.

An efficient method for the synthesis of multi-substituted pyridines from α,β-unsaturated oxime ethers via cationic Pd(ii)-catalyzed C–H activation has been developed.     

Cu-catalyzed mild and efficient oxidation of THβCs using air: application in practical total syntheses of perlolyrine and flazin

A mild, efficient and environmentally benign method for synthesis of aromatic β-carbolines via Cu(ii)-catalyzed oxidation of 1,2,3,4-tetrahydro-β-carbolines (THβCs) was developed, in which air (O₂) was used as the clean oxidant. This method has advantages such as environmentally friendliness, mildness, very good tolerance of functional groups, high yielding and easy experiment operation. In addition, this new methodology was successfully applied in the efficient and practical total syntheses of β-carboline alkaloids perlolyrine and flazin.

A mild, efficient and ecofriendly method for synthesis of β-carbolines via Cu-catalyzed aerobic oxidation of 1,2,3,4-tetrahydro-β-carbolines (THβCs) was developed. In addition, this method was successfully applied in the practical total syntheses of perlolyrine and flazin.     

Novel stereoselective syntheses of N-octyl-β-valienamine (NOV) and N-octyl-4-epi-β-valienamine (NOEV) from (−)-shikimic acid

N-Octyl-β-valienamine (NOV) 1 and N-octyl-4-epi-β-valienamine (NOEV) 2 are potent chemical chaperone drug candidates for the therapy of lysosomal storage disorders. Novel stereoselective syntheses of NOV 1 and NOEV 2 starting from naturally abundant (−)-shikimic acid are described in this article. The common key intermediate compound 5 was first synthesized from readily available (−)-shikimic acid via 9 steps in 50% yield. Compound 5 was then converted to NOV 1via 5 steps in 61% yield, and it was also converted to NOEV 2via 8 steps in 38% yield. In summary, NOV 1 was synthesized via 14 steps in 31% overall yield; and NOEV 2 was synthesized via 17 steps in 19% overall yield.

Novel stereoselective syntheses of N-octyl-β-valienamine (NOV) 1 and N-octyl-4-epi-β-valienamine (NOEV) 2 starting from naturally abundant (−)-shikimic acid are described in this article.     

Gram scale production of 1-azido-β-d-glucose via enzyme catalysis for the synthesis of 1,2,3-triazole-glucosides

The production of analytical amounts of azido sugars is used as a means of verifying catalytic acid/base mutations of retaining glycosidase, but application of this process to preparative synthesis has not been reported. The catalytic acid/base mutant of Thermoanaerobacterium xylanolyticus GH116 β-glucosidase, TxGH116D593A, catalyzed the gram scale production of 1-azido-β-d-glucose (1) from p-nitropheyl-β-d-glucopyranoside (pNPGlc) and azide via a transglucosylation reaction. Overnight reaction of the enzyme with pNPGlc and NaN₃ in aqueous MES buffer (pH 5.5) at 55 °C produced 1 (3.27 g), which was isolated as a white foamy solid in 96% yield. This 1 was successfully utilized for the synthesis of fifteen 1,2,3-triazole-β-d-glucosyl derivatives (2–16) containing a variety of functional groups, via click chemistry.

The retaining β-glucosidase acid/base mutant TxGH116D593A catalyzed the production of 1-azido-β-d-glucose for synthesis of 15 1,2,3-triazole β-glucosyl derivatives.     

The Reformatsky analogous reaction for the synthesis of novel β-thioxoesters via using aroyl isothiocyanates under solvent-free ball milling and conventional conditions

The classical Reformatsky reaction, initially described in 1887, is considered one of the most useful ways of forming C–C bonds. The target of this work includes improving the Reformatsky reaction between aroyl isothiocyanates and α-haloesters using metallic zinc to form β-thioxoesters (3–11). In this procedure, a new metal-mediated carbon–carbon linkage is formed with the formation of an organozinc halide and decomposition due to the presence of dilute acid, affording a good yield of the desired product via conventional techniques and ball milling. The Reformatsky reaction requires no solvent and no inert gases.

The Reformatsky analogous reaction between aroyl isothiocyanates and α-haloesters using metallic zinc to form β-thioxoesters via ball milling and conventional techniques.     

Removal of methylene blue dye by solvothermally reduced graphene oxide: a metal-free adsorption and photodegradation method

In this work, reduced graphene oxide (rGO) was fabricated at different reduction temperatures via an environmentally friendly solvothermal approach. The rGO formed at 160 °C clearly showed the partial restoration of the sp² hybridization brought about by the elimination of oxygenated functionalities from the surface. Owing to the augmented surface area and the band gap reduction, rGO-160 exhibited the best adsorption (29.26%) and photocatalytic activity (32.68%) towards the removal of MB dye. The effects of catalyst loading, initial concentration of dye, light intensity, and initial pH of solution were evaluated. It was demonstrated that rGO-160 could achieve a higher adsorptive removal (87.39%) and photocatalytic degradation (98.57%) of MB dye when 60 mg of catalyst, 50 ppm of dye at pH 11, and 60 W m⁻² of UV-C light source were used. The MB photodegradation activity of rGO-160 displayed no obvious decrease after five successive cycles. This study provides a potential metal-free adsorbent-cum-photocatalyst for the decontamination of dyes from wastewater.

A metal-free MB dye removal process was carried out by solvothermally synthesized rGO. After optimization, near-complete dye removal was achieved via an adsorption and UV photodegradation route.     

Combinatorial synthesis and biological evaluations of (E)-β-trifluoromethyl vinylsulfones as antitumor agents

Combinatorial synthesis of (E)-β-trifluoromethyl vinylsulfones is accomplished through a reaction of alkynes, Togni reagent, and sodium benzenesulfinates in DMSO under metal-free conditions at room temperature. These compounds are evaluated in several assays against different tumor cells. Some hits are identified against ES-2, HO-8910, and K562.

(E)-β-Trifluoromethyl vinylsulfones is accomplished through a reaction of alkynes, Togni reagent, and sodium benzenesulfinates under metal-free conditions. p-Acetylphenyl in R¹ has the best activities against several tumor cells.     

Cs2CO3 catalyzed direct aza-Michael addition of azoles to α,β-unsaturated malonates

A highly efficient method for the synthesis of azole derivatives via a direct aza-Michael addition of azoles to α,β-unsaturated malonates using Cs₂CO₃ as a catalyst, has been successfully developed. A series of azole derivatives have been obtained in up to 94% yield and the reaction could be amplified to gram scale in excellent yield in the presence of 10 mol% of Cs₂CO₃.

A highly efficient method for the synthesis of azole derivatives via a direct aza-Michael addition of azoles to α,β-unsaturated malonates has been successfully developed. A series of azole derivatives have been obtained in up to 94% yield.     

Synthesis of tetrahydro-β-carbolines from 2-indolylmethyl azides and propargylic alcohols

A facile and efficient route to tetrahydro-β-carbolines from 2-indolylmethyl azides and propargylic alcohols via acid-catalyzed dehydrative annulation reactions is described. This reaction proceeds through a cascade sequence of Friedel–Crafts-type alkylation followed by intramolecular “Click” reaction, involving the formation of multiple chemical bonds in a single operation with excellent atom-economy and broad functional group tolerance.

The synthesis of tetrahydro-β-carbolines from 2-indolylmethyl azides and propargylic alcohols via acid-catalyzed dehydrative [4 + 2]-annulation reaction is described.     

The preparation of a difunctional porous β-tricalcium phosphate scaffold with excellent compressive strength and antibacterial properties

Porous β-tricalcium phosphate (β-Ca₃(PO₄)₂, β-TCP) scaffolds are widely applied in the field of bone tissue engineering due to their nontoxicity, degradability, biocompatibility, and osteoinductivity. However, poor compressive strength and a lack of antibacterial properties have hindered their clinical application. In order to address these disadvantages, graphene (G) and silver nanoparticles were introduced into β-TCP through a two-step method. In the synthesis process, G-β-TCP was prepared via an in situ synthesis method, and then silver nanoparticles and HAp particles were coated on the surface of the G-β-TCP scaffold in an orderly fashion using dopamine as a binder. From the results of characterization, when the content of graphene was 1 wt% of β-TCP, the G-β-TCP scaffold had the highest compression strength (127.25 MPa). And core–shell G-β-TCP-Ag-HAp not only had reduced cytotoxicity via the continuous release of Ag⁺, but it also achieved long-term antibacterial properties. Besides, the material still showed good cell activity and proliferation.

Silver nanoparticles and HAp particles were orderly coated on the surface of G-β-TCP scaffold. So the composite had good compression strength and antibacterial property.     

Phosphorus pentoxide as a cost-effective,metal-free catalyst for ring opening polymerization of ε-caprolactone

The ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) using phosphorus pentoxide (P₂O₅) as a metal-free catalyst and isopropanol (iPrOH) as initiator resulted in the preparation of poly(ε-caprolactone) with narrow weight distribution. NMR spectroscopy analyses of the prepared PCL indicated the presence of the initiator residue at the end of the polymer chain, implying the occurrence of the ε-CL-catalysis ROP through a monomer activation mechanism. Kinetic experiments confirmed the controlled/living nature of ε-CL ring-opening catalyzed by phosphorus pentoxide. The commercial availability of phosphorus pentoxide and its easy-handling provide additional opportunities for polymer synthesis and nanocomposite manufacturing.

The ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) using phosphorus pentoxide (P₂O₅) as a metal-free catalyst and isopropanol (iPrOH) as initiator resulted in the preparation of poly(ε-caprolactone) with narrow weight distribution.     

Aspect ratio-controlled preparation of α-CaSO4·0.5H2O from phosphogypsum in potassium tartrate aqueous solution

In this study, a simple and efficient strategy is developed to synthesize rod-shaped α-CaSO₄·0.5H₂O crystals with tunable aspect ratio from industrial phosphogypsum only in potassium tartrate aqueous solution at a low temperature. Industrial phosphogypsum can be effectively converted into rod-shaped α-CaSO₄·0.5H₂O crystals with the assistance of potassium tartrate, and the aspect ratio of α-CaSO₄·0.5H₂O crystals gradually decreases from 52 : 1 to 1 : 1 with increasing the concentration of potassium tartrate. The formation process of the rod-shaped α-CaSO₄·0.5H₂O crystals in this system involves the dissolution of CaSO₄·2H₂O and nucleation of α-CaSO₄·0.5H₂O crystals. The tartrate ions from potassium tartrate in this system preferentially bind to (001) and (002) facets of α-CaSO₄·0.5H₂O crystals, inhibiting the growth of α-CaSO₄·0.5H₂O crystals along the c-axis and controlling its morphology and aspect ratio.

The conversion of industrial gypsum to rod-shaped α-CaSO₄·0.5H₂O crystals with tunable aspect ratio in a H₂O system is realized with potassium tartrate.     

Double nucleophilic addition to iminomalonate,leading to the synthesis of quaternary α-amino diesters and desymmetrization of the products

Alkylation of iminomalonate with Grignard reagents followed by oxidation and allylation gave symmetrical quaternary α-amino diesters in good yields. Subsequent desymmetrization of a diol derivative from these products was conducted via asymmetric carbamylation catalyzed by Cu-Bnbox to give chiral quaternary aminodiol mono-carbamates.

Alkylation of iminomalonate with Grignard reagents followed by oxidation and allylation gave symmetrical quaternary α-amino diesters. Subsequent desymmetrization of a diol derivative from these products was conducted via asymmetric carbamylation catalyzed by Cu-Bnbox.     

New α-galactosidase-inhibiting aminohydroxycyclopentanes

A set of cyclopentanoid α-galactosidase ligands was prepared from a partially protected ω-eno-aldose via a reliable (2 + 3)-cycloaddition protocol with slightly modified conditions. The obtained N-benzylisoxazolidine ring was selectively opened and the configuration of the hydroxymethylgroup was inverted. Consecutive deprotection provided an aminocyclopentane, which was N-alkylated to furnish a set of potential α-galactosidase inhibitors. Their glycosidase inhibitory activities were screened with a panel of standard glycosidases of biological significance.

A concise and robust synthesis of new cyclopentanoid competitive inhibitors of α-galactosidases related to Fabry''s disease and other α-galactosidase related disorders.     

Synthesis of hierarchical nanocrystalline β zeolite as efficient catalyst for alkylation of benzene with benzyl alcohol

To develop an efficient solid acid catalysts for the Friedel–Crafts alkylation reaction, especially for involving bulky molecules, the direct synthesis of hierarchical nanocrystalline β zeolites were achieved by using amphiphilic organosilane ([(CH₃O)₃SiC₃H₆N(CH₃)₂C₁₈H₃₇]Cl, TPOAC) as collaborative structure-directing agent (SDA). The growth evolution of β crystals and the influence of TPOAC/SiO₂ molar ratio on the mesoporous structure, crystal size, and acidic properties of β zeolites were investigated and discussed in detail. The characterization results reveal that intracrystalline mesopores and intercrystalline mesopores/macropores via the stacking of β nanocrystals were generated over the hierarchical β zeolites. Moreover, most of the strong acid sites were well remained compared with the conventional microporous β zeolite. Consequently, the hierarchical nanocrystalline β zeolite synthesized under the optimized synthesis conditions shows improved specific catalytic activity of acid sites (turnover number, TON) in alkylation of benzene with benzyl alcohol, which can be attributed to the integrated balance of considerable mesoporosity, accessibility of the acid sites, and well-remained strong acid sites in the hierarchical β zeolite.

Hierarchical β zeolite with enhanced transport and specific catalytic activity of acid sites in Friedel–Crafts alkylation was achieved by using amphiphilic organosilane surfactant as mesopores-directing agent and crystal growth inhibitor.