In Silico Approaches to Polyherbal Synergy: Protocol for a Scoping Review.

BACKGROUND: According to the World Health Organization, more than 80% of the world's population relies on traditional medicine. Traditional medicine is typically based on the use of single herbal drugs or polyherbal formulations (PHFs) to manage diseases. However, the probable mode of action of these formulations is not well studied or documented. Over the past few decades, computational methods have been used to study the molecular mechanism of phytochemicals in single herbal drugs. However, the in silico methods applied to study PHFs remain unclear. OBJECTIVE: The aim of this protocol is to develop a search strategy for a scoping review to map the in silico approaches applied in understanding the activity of PHFs used as traditional medicines worldwide. METHODS: The scoping review will be conducted based on the methodology developed by Arksey and O'Malley and the recommendations of the Joanna Briggs Institute (JBI). A set of predetermined keywords will be used to identify the relevant studies from five databases: PubMed, Embase, Science Direct, Web of Science, and Google Scholar. Two independent reviewers will conduct the search to yield a list of relevant studies based on the inclusion and exclusion criteria. Mendeley version 1.19.8 will be used to remove duplicate citations, and title and abstract screening will be performed with Rayyan software. The JBI System for the Unified Management, Assessment, and Review of Information tool will be used for data extraction. The scoping review will be reported based on the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. RESULTS: Based on the core areas of the scoping review, a 3-step search strategy was developed. The initial search produced 3865 studies. After applying filters, 875 studies were short-listed for further review. Keywords were further refined to yield more relevant studies on the topic. CONCLUSIONS: The findings are expected to determine the extent of the knowledge gap in the applications of computational methods in PHFs for any traditional medicine across the world. The study can provide answers to open research questions related to the phytochemical identification of PHFs, criteria for target identification, strategies applied for in silico studies, software used, and challenges in adopting in silico methods for understanding the mechanisms of action of PHFs. This study can thus provide a better understanding of the application and types of in silico methods for investigating PHFs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/56646.

Effect of Particle Heterogeneity in Catalytic Copper-Containing Single-Chain Polymeric Nanoparticles Revealed by Single-Particle Kinetics.

Single-chain polymeric nanoparticles (SCPNs) have been extensively explored as a synthetic alternative to enzymes for catalytic applications. However, the inherent structural heterogeneity of SCPNs, arising from the dispersity of the polymer backbone and stochastic incorporation of different monomers as well as catalytic moieties, is expected to lead to variations in catalytic activity between individual particles. To understand the effect of structural heterogeneities on the catalytic performance of SCPNs, techniques are required that permit researchers to directly monitor SCPN activity at the single-polymer level. In this study, we introduce the use of single-molecule fluorescence microscopy to study the kinetics of Cu(I)-containing SCPNs towards depropargylation reactions. We developed Cu(I)-containing SCPNs that exhibit fast kinetics towards depropargylation and Cu-catalyzed azide-alkyne click reactions, making them suitable for single-particle kinetic studies. SCPNs were then immobilized on the surface of glass coverslips and the catalytic reactions were monitored at a single-particle level using total internal reflection fluorescence (TIRF) microscopy. Our studies revealed the interparticle turnover dispersity for Cu(I)-catalyzed depropargylations. In the future, our approach can be extended to different polymer designs which can give insights into the intrinsic heterogeneity of SCPN catalysis and can further aid in the rational development of SCPN-based catalysts.

Enhanced Efficiency of Pd(0)-Based Single Chain Polymeric Nanoparticles for in Vitro Prodrug Activation by Modulating the Polymer's Microstructure.

Bioorthogonal catalysis employing transition metal catalysts is a promising strategy for the in situ synthesis of imaging and therapeutic agents in biological environments. The transition metal Pd has been widely used as a bioorthogonal catalyst, but bare Pd poses challenges in water solubility and catalyst stability in cellular environments. In this work, Pd(0) loaded amphiphilic polymeric nanoparticles are applied to shield Pd in the presence of living cells for the in situ generation of a fluorescent dye and anticancer drugs. Pd(0) loaded polymeric nanoparticles prepared by the reduction of the corresponding Pd(II)-polymeric nanoparticles are highly active in the deprotection of pro-rhodamine dye and anticancer prodrugs, giving significant fluorescence enhancement and toxigenic effects, respectively, in HepG2 cells. In addition, we show that the microstructure of the polymeric nanoparticles for scaffolding Pd plays a critical role in tuning the catalytic efficiency, with the use of the ligand triphenylphosphine as a key factor for improving the catalyst stability in biological environments.

Amphiphilic polymeric nanoparticles enable homogenous rhodium-catalysed NH insertion reactions in living cells.

Rh-catalysed NH carbene insertion reactions were exported to living cells with help of amphiphilic polymeric nanoparticles. Hereto, hydrophobic dirhodium carboxylate catalysts were efficiently encapsulated in amphiphilic polymeric nanoparticles comprising dodecyl and Jeffamine as side grafts. The developed catalytic nanoparticles promoted NH carbene insertions between α-keto diazocarbenes and 2,3-diaminonaphthalene, followed by intramolecular cyclisation to form fluorescent or biologically active benzoquinoxalines. These reactions were studied in reaction media of varying complexity. The best-performing catalyst was exported to HeLa cells, where fluorescent and cytotoxic benzoquinoxalines were synthesized in situ at low catalyst loading within a short time. Most of the developed bioorthogonal transition metal catalysts reported to date are easily deactivated by the reactive biomolecules in living cells, limiting their applications. The high catalytic efficiency of the Rh-based polymeric nanoparticles reported here opens the door to expanding the repertoire of bioorthogonal reactions and is therefore promising for biomedical applications.

Tripodal cyanurates as selective transmembrane Cl- transporters.

Tris-carboxyamide and tris-sulfonamide-based anion transporters with a cyanuric acid core are reported. Interestingly, Cl- ion binding and transmembrane transport properties of carboxyamides are better compared to those of their tris-sulfonamide analogs. The carboxyamide derivatives act as mobile carriers of Cl- and exchange anions via antiport mechanism.