Correction: Rational design of a “dual lock-and-key” supramolecular photosensitizer based on aromatic nucleophilic substitution for specific and enhanced photodynamic therapy

Correction for ‘Rational design of a “dual lock-and-key” supramolecular photosensitizer based on aromatic nucleophilic substitution for specific and enhanced photodynamic therapy’ by Kun-Xu Teng et al., Chem. Sci., 2020, 11, 9703–9711, DOI: 10.1039/D0SC01122C.

The authors regret an error in Fig. 1f. The correct image is shown below.Open in a separate windowFig. 1(f) Fluorescence decay curves of BSG and BIBSG, and the detection wavelength is 600 nm in DMSO.Additionally, there was a minor error in Fig. 4a. The correct image is shown below.Open in a separate windowFig. 4(a) Evaluation of ¹O₂ generation in HepG2 cells with DCFH-DA and SOSG. The scale bar represents 20 μm.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Rational design of an “all-in-one” phototheranostic

We report here porphodilactol derivatives and their corresponding metal complexes. These systems show promise as “all-in-one” phototheranostics and are predicated on a design strategy that involves controlling the relationship between intersystem crossing (ISC) and photothermal conversion efficiency following photoexcitation. The requisite balance was achieved by tuning the aromaticity of these porphyrinoid derivatives and forming complexes with one of two lanthanide cations, namely Gd³⁺ and Lu³⁺. The net result led to a metalloporphodilactol system, Gd-trans-2, with seemingly optimal ISC efficiency, photothermal conversion efficiency and fluorescence properties, as well as good chemical stability. Encapsulation of Gd-trans-2 within mesoporous silica nanoparticles (MSN) allowed its evaluation for tumour diagnosis and therapy. It was found to be effective as an “all-in-one” phototheranostic that allowed for NIR fluorescence/photoacoustic dual-modal imaging while providing an excellent combined PTT/PDT therapeutic efficacy in vitro and in vivo in 4T1-tumour-bearing mice.

We report here porphodilactol derivatives and their corresponding metal complexes as “all-in-one” phototheranostics by controlling the relationship between intersystem crossing (ISC) and photothermal conversion efficiency following photoexcitation.     

Albumin-mediated “Unlocking” of supramolecular prodrug-like nanozymes toward selective imaging-guided phototherapy

Construction of an activatable photosensitizer and integration into an adaptive nanozyme during phototherapy without producing off-target toxicity remains a challenge. Herein, we have fabricated a prodrug-like supramolecular nanozyme based on a metallic-curcumin and cyanine co-assembly. The albumin-mediated phenol AOH group transformation of nanozyme changes its adjustable oxygen stress from negative superoxide dismutase-like activity of ROS-scavenging to positive photo oxidase activity with an ROS-amplifying capacity. It further increases the depth penetration of a nanozyme in a tumor spheroid, selectively targeting tumorous phototherapy. It also triggers a signal in targeted tumor cells and helps increase cancer cell ablation. This work suggests new options for development of activatable supramolecular nanozymes and provides a synergetic prodrug-like nanozyme strategy for early diagnosis and preclinical phototherapeutics.

An adaptive nanozyme without producing off-target toxicity has been successfully applied in phototherapy.     

High Yield Synthesis of Curcumin and Symmetric Curcuminoids: A “Click” and “Unclick” Chemistry Approach

The worldwide known and employed spice of Asian origin, turmeric, receives significant attention due to its numerous purported medicinal properties. Herein, we report an optimized synthesis of curcumin and symmetric curcuminoids of aromatic (bisdemethoxycurcumin) and heterocyclic type, with yields going from good to excellent using the cyclic difluoro-boronate derivative of acetylacetone prepared by reaction of 2,4-pentanedione with boron trifluoride in THF (ca. 95%). The subsequent cleavage of the BF₂ group is of significant importance for achieving a high overall yield in this two-step procedure. Such cleavage occurs by treatment with hydrated alumina (Al₂O₃) or silica (SiO₂) oxides, thus allowing the target heptanoids obtained in high yields as an amorphous powder to be filtered off directly from the reaction media. Furthermore, crystallization instead of chromatographic procedures provides a straightforward purification step. The ease and efficiency with which the present methodology can be applied to synthesizing the title compounds earns the terms “click” and “unclick” applied to describe particularly straightforward, efficient reactions. Furthermore, the methodology offers a simple, versatile, fast, and economical synthetic alternative for the obtention of curcumin (85% yield), bis-demethoxycurcumin (78% yield), and the symmetrical heterocyclic curcuminoids (80–92% yield), in pure form and excellent yields.     

Click Chemistry of Melamine Dendrimers: Comparison of “Click-and-Grow” and “Grow-Then-Click” Strategies Using a Divergent Route to Diversity

Dendrimers are attractive macromolecules for a broad range of applications owing to their well-defined shapes and dimensions, highly branched and globular architectures, and opportunities for exploiting multivalency. Triazine dendrimers in particular offer advantages such as ease of synthesis, stability, well-defined spherical structure, multivalency, potential to achieve acceptable drug loadings, and low polydispersity. In this study, the potential utility of alkyne-azide “click” cycloadditions of first-, second-, and third-generation triazine dendrimers containing three or six alkynyl groups with benzyl azide was examined using copper catalysts. “Click-and-grow” and “grow-then-click” strategies were employed. For the first- and second- generation dendrimers, the desired triazole derivatives were obtained in high yields and purified by simple reprecipitation without column chromatography; however, some difficulties were observed in the preparation of third-generation dendrimers. The desired reaction proceeded under microwave irradiation as well as with simple heating. This click chemistry can be utilized for various melamine dendrimers that are fabricated with other amine linkers.     

Resources and Methods for Engineering “Designer” Glycan-Binding Proteins

This review provides information on available methods for engineering glycan-binding proteins (GBP). Glycans are involved in a variety of physiological functions and are found in all domains of life and viruses. Due to their wide range of functions, GBPs have been developed with diagnostic, therapeutic, and biotechnological applications. The development of GBPs has traditionally been hindered by a lack of available glycan targets and sensitive and selective protein scaffolds; however, recent advances in glycobiology have largely overcome these challenges. Here we provide information on how to approach the design of novel “designer” GBPs, starting from the protein scaffold to the mutagenesis methods, selection, and characterization of the GBPs.     

Characterization of Effects of Different Tea Harvesting Seasons on Quality Components,Color and Sensory Quality of “Yinghong 9” and “Huangyu” Large-Leaf-Variety Black Tea

Harvesting seasons are crucial for the physicochemical qualities of large-leaf-variety black tea. To investigate the effect of harvesting seasons on physicochemical qualities, the color and sensory characteristics of black tea produced from “Yinghong 9” (Yh) and its mutant “Huangyu” (Hy) leaves were analyzed. The results demonstrated that Hy had better chemical qualities and sensory characteristics, on average, such as a higher content of tea polyphenols, free amino acids, caffeine, galloylated catechins (GaCs) and non-galloylated catechins (NGaCs), while the hue of the tea brew (ΔE*ab and Δb*) increased, which meant that the tea brew was yellower and redder. Moreover, the data showed that the physicochemical qualities of SpHy (Hy processed in spring) were superior to those of SuHy (Hy processed in summer) and AuHy (Hy processed in autumn), and 92.6% of the total variance in PCA score plots effectively explained the separation of the physicochemical qualities of Yh and Hy processed in different harvesting seasons. In summary, Hy processed in spring was superior in its physicochemical qualities. The current results will provide scientific guidance for the production of high-quality large-leaf-variety black tea in South China.     

Facile Synthesis of Bio-Antimicrobials with “Smart” Triiodides

Multi-drug resistant pathogens are a rising danger for the future of mankind. Iodine (I₂) is a centuries-old microbicide, but leads to skin discoloration, irritation, and uncontrolled iodine release. Plants rich in phytochemicals have a long history in basic health care. Aloe Vera Barbadensis Miller (AV) and Salvia officinalis L. (Sage) are effectively utilized against different ailments. Previously, we investigated the antimicrobial activities of smart triiodides and iodinated AV hybrids. In this work, we combined iodine with Sage extracts and pure AV gel with polyvinylpyrrolidone (PVP) as an encapsulating and stabilizing agent. Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-Vis), Surface-Enhanced Raman Spectroscopy (SERS), microstructural analysis by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-Ray-Diffraction (XRD) analysis verified the composition of AV-PVP-Sage-I₂. Antimicrobial properties were investigated by disc diffusion method against 10 reference microbial strains in comparison to gentamicin and nystatin. We impregnated surgical sutures with our biohybrid and tested their inhibitory effects. AV-PVP-Sage-I₂ showed excellent to intermediate antimicrobial activity in discs and sutures. The iodine within the polymeric biomaterial AV-PVP-Sage-I₂ and the synergistic action of the two plant extracts enhanced the microbial inhibition. Our compound has potential for use as an antifungal agent, disinfectant and coating material on sutures to prevent surgical site infections.     

Synthesis and Structure of Nido-Carboranyl Azide and Its “Click” Reactions

Novel zwitter-ionic nido-carboranyl azide 9-N₃(CH₂)₃Me₂N-nido-7,8-C₂B₉H₁₁ was prepared by the reaction of 9-Cl(CH₂)₃Me₂N-nido-7,8-C₂B₉H₁₁ with NaN₃. The solid-state molecular structure of nido-carboranyl azide was determined by single-crystal X-ray diffraction. 9-N₃(CH₂)₃Me₂N-nido-7,8-C₂B₉H₁₁ was used for the copper(I)-catalyzed azide-alkyne cycloaddition with phenylacetylene, alkynyl-3β-cholesterol and cobalt/iron bis(dicarbollide) terminal alkynes to form the target 1,2,3-triazoles. The nido-carborane-cholesterol conjugate 9-3β-Chol-O(CH₂)C-CH-N₃(CH₂)₃Me₂N-nido-7,8-C₂B₉H₁₁ with charge-compensated group in a linker can be used as a precursor for preparation of liposomes for Boron Neutron Capture Therapy (BNCT). A series of novel zwitter-ionic boron-enriched cluster compounds bearing a 1,2,3-triazol-metallacarborane-carborane conjugated system was synthesized. Prepared conjugates contain a large amount of boron atom in the biomolecule and potentially can be used for BNCT.     

“On-The-Fly” Non-Adiabatic Dynamics Simulations on Photoinduced Ring-Closing Reaction of a Nucleoside-Based Diarylethene Photoswitch

Nucleoside-based diarylethenes are emerging as an especial class of photochromic compounds that have potential applications in regulating biological systems using noninvasive light with high spatio-temporal resolution. However, relevant microscopic photochromic mechanisms at atomic level of these novel diarylethenes remain to be explored. Herein, we have employed static electronic structure calculations (MS-CASPT2//M06-2X, MS-CASPT2//SA-CASSCF) in combination with non-adiabatic dynamics simulations to explore the related photoinduced ring-closing reaction of a typical nucleoside-based diarylethene photoswitch, namely, PS-IV. Upon excitation with UV light, the open form PS-IV can be excited to a spectroscopically bright S₁ state. After that, the molecule relaxes to the conical intersection region within 150 fs according to the barrierless relaxed scan of the C1–C6 bond, which is followed by an immediate deactivation to the ground state. The conical intersection structure is very similar to the ground state transition state structure which connects the open and closed forms of PS-IV, and therefore plays a crucial role in the photochromism of PS-IV. Besides, after analyzing the hopping structures, we conclude that the ring closing reaction cannot complete in the S₁ state alone since all the C1–C6 distances of the hopping structures are larger than 2.00 Å. Once hopping to the ground state, the molecules either return to the original open form of PS-IV or produce the closed form of PS-IV within 100 fs, and the ring closing quantum yield is estimated to be 56%. Our present work not only elucidates the ultrafast photoinduced pericyclic reaction of the nucleoside-based diarylethene PS-IV, but can also be helpful for the future design of novel nucleoside-based diarylethenes with better performance.     

Towards photoswitchable quadruple hydrogen bonds via a reversible “photolocking” strategy for photocontrolled self-assembly

Developing new photoswitchable noncovalent interaction motifs with controllable bonding affinity is crucial for the construction of photoresponsive supramolecular systems and materials. Here we describe a unique “photolocking” strategy for realizing photoswitchable control of quadruple hydrogen-bonding interactions on the basis of modifying the ureidopyrimidinone (UPy) module with an ortho-ester substituted azobenzene unit as the “photo-lock”. Upon light irradiation, the obtained Azo-UPy motif is capable of unlocking/locking the partial H-bonding sites of the UPy unit, leading to photoswitching between homo- and heteroquadruple hydrogen-bonded dimers, which has been further applied for the fabrication of novel tunable hydrogen bonded supramolecular systems. This “photolocking” strategy appears to be broadly applicable in the rational design and construction of other H-bonding motifs with sufficiently photoswitchable noncovalent interactions.

A photolocking strategy is described to achieve the construction of effectively photoswitchable quadruple hydrogen bonds featuring with photoregulable H-bonding affinities, which is further applied in the photocontrollable H-bonded self-assemblies.     

Understanding how Lewis acids dope organic semiconductors: a “complex” story

We report on computational studies of the potential of three borane Lewis acids (LAs) (B(C₆F₅)₃ (BCF), BF₃, and BBr₃) to form stable adducts and/or to generate positive polarons with three different semiconducting π-conjugated polymers (PFPT, PCPDTPT and PCPDTBT). Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations based on range-separated hybrid (RSH) functionals provide insight into changes in the electronic structure and optical properties upon adduct formation between LAs and the two polymers containing pyridine moieties, PFPT and PCPDTPT, unravelling the complex interplay between partial hybridization, charge transfer and changes in the polymer backbone conformation. We then assess the potential of BCF to induce p-doping in PCPDTBT, which does not contain pyridine groups, by computing the energetics of various reaction mechanisms proposed in the literature. We find that reaction of BCF(OH₂) to form protonated PCPDTBT and [BCF(OH)]⁻, followed by electron transfer from a pristine to a protonated PCPDTBT chain is highly endergonic, and thus unlikely at low doping concentration. The theoretical and experimental data can, however, be reconciled if one considers the formation of [BCF(OH)BCF]⁻ or [BCF(OH)(OH₂)BCF]⁻ counterions rather than [BCF(OH)]⁻ and invokes subsequent reactions resulting in the elimination of H₂.

Here we report on DFT calculations investigating the mechanistic aspects in doping organic semiconductors by the use of Lewis acids. Our results highlight the role played by the formation of diboron-containing bridged anions in the doping mechanism.     

Accurate prediction of chemical shifts for aqueous protein structure on “Real World” data

Here we report a new machine learning algorithm for protein chemical shift prediction that outperforms existing chemical shift calculators on realistic data that is not heavily curated, nor eliminates test predictions ad hoc. Our UCBShift predictor implements two modules: a transfer prediction module that employs both sequence and structural alignment to select reference candidates for experimental chemical shift replication, and a redesigned machine learning module based on random forest regression which utilizes more, and more carefully curated, feature extracted data. When combined together, this new predictor achieves state-of-the-art accuracy for predicting chemical shifts on a randomly selected dataset without careful curation, with root-mean-square errors of 0.31 ppm for amide hydrogens, 0.19 ppm for Hα, 0.84 ppm for C′, 0.81 ppm for Cα, 1.00 ppm for Cβ, and 1.81 ppm for N. When similar sequences or structurally related proteins are available, UCBShift shows superior native state selection from misfolded decoy sets compared to SPARTA+ and SHIFTX2, and even without homology we exceed current prediction accuracy of all other popular chemical shift predictors.

UCBShift predicts NMR chemical shifts of proteins that exceeds accuracy of other popular chemical shift predictors on real-world data sets.     

Improving Catalytic Activity of “Janus” MoSSe Based on Surface Interface Regulation

The monolayer Janus MoSSe is considered to be a promising catalytic material due to its unique asymmetric structure. In order to improve its catalytic performance for hydrogen evolution reactions (HERs) and oxygen evolution reactions (OERs), many attempts have been made. In this work, a series of transition metal (TM) atoms were anchored on the Janus MoSSe surface to screen effective TM single-atom catalysts for HERs and OERs through density functional theory (DFT) calculations. Fe@MoSSe presents excellent HERs performance and Ni@MoSSe presents excellent catalytic performance for OERs with extremely low over-potential of 0.32 V. The enhanced activity is attributed to the modest energy level of the d band center of the transition metal atom, and the transition metal atom improves the conductivity of the original MoSSe and offers unoccupied states near the Fermi level. At the same time, the anchoring of transition metal atoms redistributes the charge in the MoSSe system, which effectively regulates the electronic structure of the material itself. The strain calculation shows that the activity of the catalyst can be improved by reasonably adjusting the value of the applied strain.     

Metabolite Profiling of “Green” Extracts of Cynara cardunculus subsp. scolymus,Cultivar “Carciofo di Paestum” PGI by 1H NMR and HRMS-Based Metabolomics

Globe artichoke (Cynara cardunculus L. var. scolymus L.), is a perennial plant widely cultivated in the Mediterranean area, known for its edible part named capitula or heads. Its functional properties are related to its high levels of polyphenolic compounds and inulin. “Carciofo di Paestum”, an Italian traditional cultivar, is a labeled PGI (Protected Geographical Indication) product of the Campania region, representing an important economic resource. So far, a few chemical investigations were performed on this cultivar, mainly focused on the analysis of methanol extracts. Due to the increasing use of food supplements, in this study, a comprehensive analysis of green extracts of “Carciofo di Paestum” PGI heads was performed. EtOH, EtOH: H₂O (80:20, 70:30, 60:40) extracts, as well as infusions and decoctions prepared according to Pharmacopeia XII were analyzed by LC-ESI/QExactive/MS/MS. A total of 17 compounds corresponding to caffeoylquinic acid derivatives, phenolics, flavonoids, and terpenoids were identified. The extracts were further submitted to NMR analysis to highlight the occurrence of primary metabolites. Both LCMS and NMR data were analyzed by Principal Component Analysis (PCA), showing significant differences among the extraction methods. Moreover, 5-caffeoylquinic acid and 1,5-dicaffeoylquinic acid were quantified in the extracts by LC-ESI/QTrap/MS/MS using the Multiple Reaction Monitoring (MRM) method. Furthermore, the phenolic content, antioxidant activity, and α-glucosidase inhibitory activity of C. cardunculus var. scolymus “Carciofo di Paestum” extracts were evaluated.     

Microwaves as “Co-Catalysts” or as Substitute for Catalysts in Organophosphorus Chemistry

The purpose of this review is to summarize the importance of microwave (MW) irradiation as a kind of catalyst in organophosphorus chemistry. Slow or reluctant reactions, such as the Diels-Alder cycloaddition or an inverse-Wittig type reaction, may be performed efficiently under MW irradiation. The direct esterification of phosphinic and phosphonic acids, which is practically impossible on conventional heating, may be realized under MW conditions. Ionic liquid additives may promote further esterifications. The opposite reaction, the hydrolysis of P-esters, has also relevance among the MW-assisted transformations. A typical case is when the catalysts are substituted by MWs, which is exemplified by the reduction of phosphine oxides, and by the Kabachnik–Fields condensation affording α-aminophosphonic derivatives. Finally, the Hirao P–C coupling reaction may serve as an example, when the catalyst may be simplified under MW conditions. All of the examples discussed fulfill the expectations of green chemistry.