Construction of Multi-Enzyme Integrated Catalysts for Deracemization of Cyclic Chiral Amines.

Multi-enzyme cascade catalysis has become an important technique for chemical reactions used in manufacturing and scientific study. In this research, we designed a four-enzyme integrated catalyst and used it to catalyse the deracemization reaction of cyclic chiral amines, where monoamine oxidase (MAO) catalyses the enantioselective oxidation of 1-methyl-1,2,3,4-tetrahydroisoquinoline (MTQ), imine reductase (IRED) catalyses the stereo selective reduction of 1-methyl-3,4-dihydroisoquinoline (MDQ), formate dehydrogenase (FDH) is used for the cyclic regeneration of cofactors, and catalase (CAT) is used for decomposition of oxidative reactions. The four enzymes were immobilized via polydopamine (PDA)-encapsulated dendritic organosilica nanoparticles (DONs) as carriers, resulting in the amphiphilic core-shell catalysts. The hydrophilic PDA shell ensures the dispersion of the catalyst in water, and the hydrophobic DON core creates a microenvironment with the spatial confinement effect of the organic substrate and the preconcentration effect to enhance the stability of the enzymes and the catalytic efficiency. The core-shell structure improves the stability and reusability of the catalyst and rationally arranges the position of different enzymes according to the reaction sequence to improve the cascade catalytic performance and cofactor recovery efficiency.

Monitoring of singlet oxygen generation of a novel Schiff-base substituted silicon phthalocyanines by sono-photochemical studies and in vitro activities on prostate cancer cell.

This study demonstrates the potential of sono-photodynamic therapy as an effective approach for enhancing singlet oxygen generation using the synthesized Schiff-base diaxially substituted silicon phthalocyanines. In photochemical studies, the singlet oxygen quantum yields (Φ∆) were determined as 0.43 for Si1a, 0.94 for Q-Si1a, 0.58 for S-Si1a, and 0.49 for B-Sia1. In sono-photochemical studies, the Φ∆ values were reached to 0.67 for Si1a, 1.06 for Q-Si1a, 0.65 for S-Si1a, and 0.67 for B-Sia1. In addition, this study demonstrates the therapeutic efficacy of phthalocyanines synthesized as sensitizers on the PC3 prostate cancer cell line through in vitro experiments. The application of these treatment modalities exhibited notable outcomes, leading to a substantial decrease in cell viability within the PC3 prostate cancer cell line. These findings highlight the potential of utilizing these synthesized phthalocyanines as promising therapeutic agents for prostate cancer treatment.

Redox/pH Dual-Responsive Fluorescent Nanoparticles for Intelligent Pesticide Release and Visualization in Gray Mold Disease Synergistic Control.

An intelligent delivery nanoformulation could enhance the utilization efficacy, uptake, and translocation of pesticides in plants. Herein, a redox/pH-triggered and fluorescent smart delivery nanoformulation was designed and constructed by using hollow mesoporous organosilica nanoparticles (HMONs) and ZnO quantum dots as the nanocarrier and capping agent, respectively. Boscalid was further loaded to generate Boscalid@HMONs@ZnO with a loading rate of 9.8% for controlling Botrytis cinerea (B. cinerea). The quantity of boscalid released by Boscalid@HMONs@ZnO in a glutathione environment or at pH 3.0 was 1.3-fold and 1.9-fold higher than that in a neutral condition. Boscalid@HMONs@ZnO has 1.7-fold the toxicity index of boscalid technical against B. cinerea in antifungal experiments. Pot experiments revealed that the efficacy of Boscalid@HMONs@ZnO was significantly enhanced more than 1.27-fold compared to commercially available water-dispersible granules of boscalid. Due to the fluorescence properties of Boscalid@HMONs@ZnO, pesticide transport's real-time monitoring of pesticide translocation in tomato plants could be observed by confocal laser scanning microscopy. Fluorescence images revealed that HMONs@ZnO had been effectively transported via treated leaves or roots in tomato plants. This research showed the successful application of HMONs@ZnO as a nanocarrier for controlling disease and offered an effective avenue to explore the real-time tracking of pesticide translocation in plants.

POSS and PEG Contained Copolymer for Antibioadhesive Rigid Contact Lenses Materials Application.

Myopia is a global public health issue. Rigid contact lenses (RCLs) are an effective way to correct or control myopia. However, bioadhesion issues remain one of the significant obstacles limiting its clinical application. Although enhancing hydrophilicity through various surface treatments can mitigate this problem, the duration of effectiveness is short-lived and the processing involved is complex and costly. Herein, an antiadhesive RCLs material was designed via 8-armed methacrylate-POSS (8MA-POSS), and poly(ethylene glycol) methacrylate (PEGMA) copolymerization with 3-[tris(trimethylsiloxy)silyl] propyl methacrylate (TRIS). The POSS and PEG segments incorporated P(TRIS-co-PEGMA-co-8MA-POSS) (PTPM) material was obtained and their optical transparency, refractive index, resolution, hardness, surface charge, thermal features, and wettability were tested and optimized. The antibioadhesion activities, including protein, lipid, and bacteria, were evaluated as well. In vitro and in vivo results indicated that the optimized antibioadhesive PTPM materials present good biocompatibility and biosafety. Thus, such POSS and PEG segments containing material were a potential antibioadhesive RCL material option.

Super-assembled periodic mesoporous organosilica membranes with hierarchical channels for efficient glutathione sensing.

Bioinspired nanochannel-based sensors have elicited significant interest because of their excellent sensing performance, and robust mechanical and tunable chemical properties. However, the existing designs face limitations due to material constraints, which hamper broader application possibilities. Herein, a heteromembrane system composed of a periodic mesoporous organosilica (PMO) layer with three-dimensional (3D) network nanochannels is constructed for glutathione (GSH) detection. The unique hierarchical pore architecture provides a large surface area, abundant reaction sites and plentiful interconnected pathways for rapid ionic transport, contributing to efficient and sensitive detection. Moreover, the thioether groups in nanochannels can be selectively cleaved by GSH to generate hydrophilic thiol groups. Benefiting from the increased hydrophilic surface, the proposed sensor achieves efficient GSH detection with a detection limit of 1.2 µM by monitoring the transmembrane ionic current and shows good recovery ranges in fetal bovine serum sample detection. This work paves an avenue for designing and fabricating nanofluidic sensing systems for practical and biosensing applications.

Heavy atom-induced quenching of fluorescent organosilicon nanoparticles for iodide sensing and total antioxidant capacity assessment.

We present a novel approach for iodide sensing based on the heavy-atom effect to quench the green fluorescent emission of organosilicon nanoparticles (OSiNPs). The fluorescence of OSiNPs was significantly quenched (up to 97.4% quenching efficiency) in the presence of iodide ions (I-) through oxidation by hydrogen peroxide. Therefore, OSiNPs can serve as a fluorescent probe to detect I- with high selectivity and sensitivity. The highly selective response is attributed to the hydrophilic surface enabling good dispersion in aqueous solutions and the lipophilic core allowing the generated liposoluble I2 to approach and quench the fluorescence of OSiNPs. The linear working range for I- was from 0 to 50 µM, with a detection limit of 0.1 µM. We successfully applied this nanosensor to determine iodine content in edible salt. Furthermore, the fluorescent OSiNPs can be utilized for the determination of total antioxidant capacity (TAC). Antioxidants reduce I2 to I-, and the extent of quenching by the remaining I2 on the OSiNPs indicates the TAC level. The responses to ascorbic acid, pyrogallic acid, and glutathione were investigated, and the detection limit for ascorbic acid was as low as 0.03 µM. It was applied to the determination of TAC in ascorbic acid tablets and fruit juices, indicating the potential application of the OSiNP-based I2 sensing technique in the field of food analysis.

Magnetically modified-mitoxantrone mesoporous organosilica drugs: an emergent multimodal nanochemotherapy for breast cancer.

BACKGROUND: Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients' quality of life, side effects limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge. RESULTS: In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, Fe3O4 NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs. CONCLUSIONS: A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated Fe3O4 into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy.

Functionalization of Siloxanes with Arynes Generated from o-Triazenylarylboronic Acids.

Herein, we report the functionalization of polyhedral oligosilsesquioxanes (POSS) and related siloxanes with arynes. Using o-triazenylarylboronic acids as aryne precursors and silica gel as the activator, the transformation of siloxane bearing various arynophilic moieties on the side chains was achieved with high yields without touching the siloxane core. This method was applied to the conjugation of POSS and pharmaceutical cores using an aryne derived from the synthetic intermediate of cabozantinib. Furthermore, orthogonal dual functionalization of POSS was realized by combining the aryne reaction with Huisgen cyclization.

SilE-R and SilE-S-DABB Proteins Catalying Enantiospecific Hydrolysis of Organosilyl Ethers.

Silyl ethers fulfil a fundamental role in synthetic organic chemistry as protecting groups and their selective cleavage is an important factor in their application. We present here for the first time two enzymes, SilE-R and SilE-S, which are able to hydrolyse silyl ethers. They belong to the stress-response dimeric A/B barrel domain (DABB) family and are able to cleave the Si-O bond with opposite enantiopreference. Silyl ethers containing aromatic, cyclic or aliphatic alcohols and, depending on the alcohol moiety, silyl functions as large as TBDMS are accepted. The X-ray crystal structure of SilE-R, determined to a resolution of 1.98 Å, in combination with mutational studies, revealed an active site featuring two histidine residues, H8 and H79, which likely act synergistically as nucleophile and Brønsted base in the hydrolytic mechanism, which has not previously been described for enzymes. Although the natural function of SilE-R and SilE-S is unknown, we propose that these 'silyl etherases' may have significant potential for synthetic applications.

Periodic Mesoporous Organosilica Nanomaterials with Unconventional Structures and Properties.

Periodic mesoporous organosilicas (PMOs) are high surface area organic-inorganic hybrid nanomaterials that have found broad applications in various fields of research such as in (bio)chemistry or material science. By choosing suitable organic groups in the framework of these materials, their surface properties such as polarity, optical/electrical characteristics and adsorption capacity can be tuned. This critical review provides an overview of the current state of the art in the developments and applications of some PMO nanomaterials in diverse fields of research. This is placed in the context of four leading areas of PMO nanomaterials, including chiral PMOs, plugged PMO nanomaterials, Janus PMOs and PMO-based nanomotors. The review briefly discusses the recent and key findings on these PMO nanomaterials as well as their potential applications for future developments.

Regioisomeric Giant Triblock Molecules: Role of the Linker.

In this study, polyhedral oligomeric silsesquioxane (POSS) based giant triblock molecules with precisely defined regio-configuration are modularly prepared through highly efficient coupling reactions. The length of the linker connecting neighboring nanoparticles is elaborately designed to regulate the geometric constraints. The triblock molecules adopt a folded packing during phase separation, and the regio-configuration imparts direct influence on the self-assembly behaviors. The ortho-isomers form periodic structures with a larger domain size, larger interfacial curvature, and enhanced phase stability. The regio-effect is closely related to the length and symmetry of the linker. As the linker extends, the neighboring particles gradually decouple, and the regio-effect diminishes. The symmetry of the linker shows an even more profound impact. This work quantitatively scrutinized the role of the linker, opening an avenue for engineering the assembled structures with molecular precision.

Effect of Axial Ligand Length on Biological and Anticancer Properties of Axially Disubstituted Silicon Phthalocyanines.

In this study, three new axially disubstituted silicon phthalocyanines (SiPc1-3) and their quaternized phthalocyanine derivatives (QSiPc1-3) were prepared and characterized. The biological properties (antioxidant, antimicrobial, antibiofilm, and microbial cell viability activities) of the water-soluble silicon phthalocyanines were examined, as well. A 1 % DMSO diluted with pure water was used as a solvent in biological activity studies. All the compounds exhibited high antioxidant activity. They displayed efficient antimicrobial and antimicrobial photodynamic therapeutic properties against various microorganisms, especially Gram (+) bacteria. Additionally, they demonstrated high antibiofilm activities against S. aureus and P. aeruginosa. In addition, 100 % bacterial reduction was obtained for all the studied phthalocyanines against E. coli viable cells. Besides, the DNA cleavage and binding features of compounds (QSiPc1-3) were studied using pBR322 DNA and CT-DNA, respectively. Furthermore, the human topoisomerase I enzyme inhibition activities of compounds QSiPc1-3 were studied. Anticancer properties of the water-soluble compounds were investigated using cell proliferation MTT assay. They exhibited anticarcinogenic activity against the human colon cancer cell line (DLD-1). Compounds QSiPc1 and QSiPc3 displayed a high anticarcinogenic effect on the DLD-1 cell line. The obtained results indicated that all the studied compounds may be effective biological agents and anticancer drugs after further investigations.

POSS-based fluorescence sensor for rapid analysis of ß-carotene in health products.

In recent years, fluorescent organic-inorganic hybrid nanomaterials have received much interest as potential fluorescent sensor materials. In this study, fluorescent organic-inorganic hybrid nanomaterials (POSS@ANT) were created using polyhedral oligomeric silsesquioxane as the precursor and 9,10-bromoanthracene as the monomer. The morphology and composition of POSS@ANT, as well as its pore characteristics and fluorescence properties were studied. POSS@ANT displayed steady fluorescence emission at an excitation wavelength of 374 nm. Next, a ß-carotene fluorescence sensor was developed using the capacity of ß-carotene to quench the fluorescence of POSS@ANT. The quenching process is linked to acceptor electron transfer and energy transfer, and the sensor has a high selectivity for ß-carotene. This ß-carotene fluorescence analysis method that we established has a linear range of 0.2-4.3 mg/L and a detection limit of 0.081 mg/L. Finally, it was used to quantify ß-carotene in health products, the recovery rate was 91.1-109.9%, the relative standard deviation (RSD) was 2.2-4.3%, and the results were comparable with the results of high-performance liquid chromatography. The approach is reliable and can be used to determine ß-carotene in health products.

Improving sorption performance of a molecularly imprinted monolithic column by doping mesoporous molecular sieve SBA-15.

For the first time a hybrid molecularly imprinted polymer (MIP) doped with 3-(trimethoxysilyl) propyl methacrylate (γ-MPS)-modified mesoporous molecular sieve SBA-15 for target peptide recognition has been developed. Zinc acrylate and methacrylic acid were used as binary functional monomers, and ethylene dimethacrylate was used as cross-linking agent to prepare an imprinted monolith against Val-Tyr-Ala-Leu-Lys(glutarylation) (VYALKglu). The morphology of the polymers was characterized by scanning electron microscopy, FT-IR spectroscopy, energy dispersive spectroscopy, and 1H NMR. The SBA-15-MPS MIP showed high recovery of 87.1% and the IF of 12.9 for the enrichment of the template peptide. When the template peptide concentration ranged from 5 to 90 µg mL-1, the correlation coefficients (R2) for the calibration function obtained was better 0.999. The limit of detection (LOD, 0.30 µg mL-1) and limit of quantification (LOQ, 1.0 µg mL-1) were achieved for signal-to-noise ratios of 3:1 and 10:1, respectively. When other kinds of synthetic peptides were used as analogs, the selectivity of the SBA-15-MPS MIP was much better than the SBA-15-MPS NIP (without template peptides) with relative selectivity coefficients of 52.8-265. In contrast, little quinolones and biogenic amines are adsorbed with the SBA-15-MPS MIP. The SBA-15-MPS MIP could enrich VYALKglu from spiked histone digestion with the average recovery of 87.8% and the relative standard deviation (RSD) of 0.99%. As a conclusion, doping of SBA-15 is an effective approach to the improvement of performance of molecularly imprinted monolith.

Design of Fluorescent Hybrid Materials Based on POSS for Sensing Applications.

Polyhedral oligomeric silsesquioxane (POSS) has a nanoscale silicon core and eight organic functional groups on the surface, with sizes from 0.7 to 1.5 nm. The three-dimensional nanostructures of POSS can be used to build all types of hybrid materials with specific performance and controllable nanostructures. The applications of POSS-based fluorescent materials have spread across various fields. In particular, the employment of POSS-based fluorescent materials in sensing application can achieve high sensitivity, selectivity, and stability. As a result, POSS-based fluorescent materials are attracting increasing attention due to their fascinating vistas, including unique structural features, easy fabrication, and tunable optical properties by molecular design. Here, we summarize the current available POSS-based fluorescent materials from design to sensing applications. In the design section, we introduce synthetic strategies and structures of the functionalized POSS-based fluorescent materials, as well as photophysical properties. In the application section, the typical POSS-based fluorescent materials used for the detection of various target objects are summarized with selected examples to elaborate on their wide applications.

Ketone Enolization with Sodium Hexamethyldisilazide: Solvent- and Substrate-Dependent E-Z Selectivity and Affiliated Mechanisms.

Ketone enolization by sodium hexamethyldisilazide (NaHMDS) shows a marked solvent and substrate dependence. Enolization of 2-methyl-3-pentanone reveals E-Z selectivities in Et3N/toluene (20:1), methyl-t-butyl ether (MTBE, 10:1), N,N,N',N″,N″-pentamethyldiethylenetriamine (PMDTA)/toluene (8:1), TMEDA/toluene (4:1), diglyme (1:1), DME (1:22), and tetrahydrofuran (THF) (1:90). Control experiments show slow or nonexistent stereochemical equilibration in all solvents except THF. Enolate trapping with Me3SiCl/Et3N requires warming to -40 °C whereas Me3SiOTf reacts within seconds. In situ enolate trapping at -78 °C using preformed NaHMDS/Me3SiCl mixtures is effective in Et3N/toluene yet fails in THF by forming (Me3Si)3N. Rate studies show enolization via mono- and disolvated dimers in Et3N/toluene, disolvated dimers in TMEDA, trisolvated monomers in THF/toluene, and free ions with PMDTA. Density functional theory computations explore the selectivities via the E- and Z-based transition structures. Failures of theory-experiment correlations of ionic fragments were considerable even when isodesmic comparisons could have canceled electron correlation errors. Swapping 2-methyl-3-pentanone with a close isostere, 2-methylcyclohexanone, causes a fundamental change in the mechanism to a trisolvated-monomer-based enolization in THF.

Peptide Bond Formation of Amino Acids by Transient Masking with Silylating Reagents.

A one-pot peptide bond-forming reaction has been developed using unprotected amino acids and peptides. Two different silylating reagents, HSi[OCH(CF3)2]3 and MTBSTFA, are instrumental for the successful implementation of this approach, being used for the activation and transient masking of unprotected amino acids and peptides at C-termini and N-termini, respectively. Furthermore, CsF and imidazole are used as catalysts, activating HSi[OCH(CF3)2]3 and also accelerating chemoselective silylation. This method is versatile as it tolerates side chains that bear a range of functional groups, while providing up to >99% yields of corresponding peptides without any racemization or polymerization.

Lewis Basic Salt-Promoted Organosilane Coupling Reactions with Aromatic Electrophiles.

Lewis basic salts promote benzyltrimethylsilane coupling with (hetero)aryl nitriles, sulfones, and chlorides as a new route to 1,1-diarylalkanes. This method combines the substrate modularity and selectivity characteristic of cross-coupling with the practicality of a base-promoted protocol. In addition, a Lewis base strategy enables a complementary scope to existing methods, employs stable and easily prepared organosilanes, and achieves selective arylation in the presence of acidic functional groups. The utility of this method is demonstrated by the synthesis of pharmaceutical analogues and its use in multicomponent reactions.

Desilylation Induced by Metal Fluoride Nanocrystals Enables Cleavage Chemistry In Vivo.

Metal fluoride nanocrystals are widely used in biomedical studies owing to their unique physicochemical properties. The release of metal ions and fluorides from nanocrystals is intrinsic due to the solubility equilibrium. It used to be considered as a drawback because it is related to the decomposition and defunction of metal fluoride nanocrystals. Many strategies have been developed to stabilize the nanocrystals, and the equilibrium concentrations of fluoride are often <1 mM. Here we make good use of this minimum amount of fluoride and unveil that metal fluoride nanocrystals could effectively induce desilylation cleavage chemistry, enabling controlled release of fluorophores and drug molecules in test tubes, living cells, and tumor-bearing mice. Biocompatible PEG (polyethylene glycol)-coated CaF2 nanocrystals have been prepared to assay the efficiency of desilylation-induced controlled release of functional molecules. We apply the strategy to a prodrug activation of monomethyl auristatin E (MMAE), showing a remarkable anticancer effect, while side effects are almost negligible. In conclusion, this desilylation-induced cleavage chemistry avails the drawback on empowering metal fluoride nanocrystals with a new function of perturbing or activating for further biological applications.

Endoscopic near-infrared photoimmunotherapy in an orthotopic head and neck cancer model.

Near-infrared photoimmunotherapy (NIR-PIT) is a cell selective cancer therapy that uses an antibody-photoabsorber (IRDye700DX, IR700) conjugate (APC) and NIR light. NIR-PIT targeting epidermal growth factor receptor (EGFR) in head and neck cancer (HNC) was conditionally approved in Japan in 2020. APC-bound tumors can be detected using endoscopic fluorescence imaging, whereas NIR light can be delivered using endoscopic fiber optics. The aims of this study were: (1) to assess the feasibility of endoscopic NIR-PIT in an orthotopic HNC model using a CD44-expressing MOC2-luc cell line; and (2) to evaluate quantitative fluorescence endoscopic imaging prior to and during NIR-PIT. The results were compared in 3 experimental groups: (1) untreated controls, (2) APC injection without light exposure (APC-IV), and (3) APC injection followed by NIR light exposure (NIR-PIT). APC injected groups showed significantly higher fluorescence signals for IR700 compared with the control group prior to therapeutic NIR light exposure, and the fluorescence signal significantly decreased in the NIR-PIT group after light exposure. After treatment, the NIR-PIT group showed significantly attenuated bioluminescence compared with the control and the APC-IV groups. Histology demonstrated diffuse necrotic death of the cancer cells in the NIR-PIT group alone. In conclusion, endoscopically delivered light combined with quantitative fluorescence imaging can be used to "see and treat" HNC. This method could also be applied to other types of cancer approachable with endoscopy.