Consecutive chirality transfer: efficient synthesis of chiral C,O-chelated BINOL/gold(iii) complexes for asymmetric catalysis and chiral resolution of disubstituted BINOLs.

A novel approach for efficient synthesis of chiral C,O-chelated BINOL/gold(iii) complexes by diastereomeric resolution using enantiopure BINOL as a chiral resolving agent was demonstrated. The BINOL/gold(iii) diastereomers with different solubility were separated by simple filtration, providing optically pure BINOL/gold(iii) complexes with up to >99 : 1 dr. By combining this with an efficient BINOL ligand dissociation process, a simple and column-free method for chiral resolution of racemic gold(iii) dichloride complexes on a gram scale was established, affording their enantiopure forms in good yields. Conversely, the resolved enantiopure gold(iii) dichloride complexes could serve as chiral resolving agents to resolve disubstituted BINOL derivatives, achieving both BINOLs and gold(iii) complexes in good to excellent yields (overall 77-96% and 76-95%, respectively) with a high optical purity of up to 99% ee. Through a consecutive chirality transfer process, the chiral information from an inexpensive chiral source was transferred to highly valuable gold(iii) complexes, followed by sterically bulky BINOL derivatives. This work would open a new synthetic strategy facilitating the development of structurally diverse chiral gold(iii) complexes and gold(iii)-mediated chiral resolution of BINOL derivatives. In addition, this new class of C,O-chelated BINOL/gold(iii) complexes achieved asymmetric carboalkoxylation of ortho-alkynylbenzaldehydes with an excellent enantioselectivity of up to 99% ee.

Modular synthesis of pentacyclic-fused pyranoquinoliziniums as organelle-selective fluorescent probes.

On basis of their unique chemical and photophysical properties, and excellent biological activities, quinoliziniums have been widely used in various research fields. Herein, modular synthetic strategies for efficient synthesis of novel fluorescent quinoliziniums by using one-pot and stepwise rhodium(III)-catalyzed C-H annulations were developed. In the one-pot synthesis, the reaction between 2-aryl-4-quinolones (1) and 1,2-diarylalkynes (2) proceeded in a chemo- and regioselective manner to give quinolinone-fused isoquinolines (3) and pentacyclic-fused pyranoquinoliziniums (4). The structural diversity of pentacyclic-fused pyranoquinoliziniums (4) was expanded by the stepwise synthesis from 3 and 2, allowing the strategic incorporation of electron-donating (OMe and OH) and electron-withdrawing (Cl) substituents on the top and bottom parts of the pyranoquinoliziniums (4). These newly synthesized pyranoquinoliziniums (4) exhibited tunable absorptions (455-532 nm), emissions (520-610 nm), fluorescence lifetime (0.3-5.6 ns), large Stokes shifts (up to 120 nm), and excellent fluorescence quantum yields (up to 0.73) upon adjusting the different substituents. The the unique arrangement of N and O atoms and extended π-conjugation of 4 could cause the relocation of HOMO comparing with our previous quinoliziniums. Importantly, pyranoquinoliziniums (4a-4g and 4i) targeted the mitochondria, while 4h was localized in lysosome. Due to the remarkable photophysical properties and the potential for organelle targeting of the novel class of quinoliziniums, they could be further applied for biological, chemical and material applications.

Controlled Supramolecular Assemblies of Chiral Cyclometalated Gold (III) Amphiphiles in Aqueous Media.

Gold (III) cyclometalated based amphiphiles in aqueous media have been revealed with excellent supramolecular transformations to external stimuli to open new pathways for soft functional material fabrications. Herein, we report a new chiral cyclometalated gold (III) amphiphile (GA) assembling into lamellar nanostructures in aqueous media confirmed with transmission electron microscopy (TEM). Counterion exchange with D-, L-, or racemic-camphorsulfonates features the significant supramolecular helicity enhancements, enabling transformations of GA from lamellar structure to vesicles and to nanotubes with multi-equivalents of counterion. The limited cytotoxicity of GA in aqueous media exhibits good biocompatibility.

Controlled Supramolecular Assemblies of Chiral Cyclometalated Gold (III) Amphiphiles in Aqueous Media.

Invited for this month's cover are the collaborating groups of Prof. Man-Kin Wong and Dr. Franco King-Chi Leung from The Hong Kong Polytechnic University. The cover picture illustrates chiral gold (III) amphiphiles assemble into tubular supramolecular structures in aqueous media through counterion controlled pathway. The nanostructures were further demonstrated with good cytocompatibility in aqueous media. More information can be found in the Research Article by Man-Kin Wong, Franco King-Chi Leung, and co-workers.

Effect of prehabilitation-related DIETary protein intake on Quality of Recovery after elective cardiac surgery (DIETQoR) study: protocol of a randomised controlled trial.

INTRODUCTION: Protein malnutrition is associated with higher risks of postoperative complications, mortality, prolonged postoperative stays in hospital, slower physical and mental recovery after surgery and lower subsequent health-related quality of life. To reduce the risk of postoperative morbidity and mortality, nutritional prehabilitation programmes have been developed recently to build up patient's nutritional reserve to withstand the stress of surgery. The intervention involves nutritional screening and counselling, and increasing dietary protein intake in protein-malnourished patients in the several weeks before surgery. However, there are few well-conducted preoperative studies to examine the effect of increasing dietary protein intake on the quality of recovery of malnourished patients after elective cardiac surgery. METHOD AND ANALYSIS: This randomised controlled trial of malnourished patients undergoing major elective cardiac surgery will compare the quality of postoperative recovery in patients with or without nutritional prehabilitation. One hundred and thirty-two patients will be randomised to receive nutritional prehabilitation (target-adjusted whey protein powder supplementation and an individualised 1 hour session/week counselling by a dietician 1 month before operation date) or standard care (no nutritional prehabilitation). Primary outcomes will be the quality of recovery after surgery (15-item Quality of Recovery) on the third postoperative day. Secondary outcomes will include days (alive and) at home within 30 days, changes in the WHO Disability Assessment Schedule 2.0, changes in health-related quality of life (EQ-5D) and Cardiac Postoperative Morbidity Survey. An outcomes assessor will be blinded to the treatment allocation. Appropriate univariate analyses, generalised estimating equations and multiple regressions will be performed for intention-to-treat and per-protocol analyses. ETHICS AND DISSEMINATION: The Joint CUHK-NTEC Clinical Research Ethics Committee approved the study protocol (CREC Ref. No.: 2021.703 T). The findings will be presented at scientific meetings, peer-reviewed journals and to study participants. TRIAL REGISTRATION NUMBER: ChiCTR2200057463.

Development and Recent Advances in Lysine and N-Terminal Bioconjugation for Peptides and Proteins.

The demand for creation of protein diversity and regulation of protein function through native protein modification and post-translational modification has ignited the development of selective chemical modification methods for peptides and proteins. Chemical bioconjugation offers selective functionalization providing bioconjugates with desired properties and functions for diverse applications in chemical biology, medicine, and biomaterials. The amino group existing at the lysine residue and N-terminus of peptides and proteins has been extensively studied in bioconjugation because of its good nucleophilicity and high surface exposure. Herein, we review the development of chemical methods for modification of the amino groups on lysine residue and N-terminus featuring excellent selectivity, mild reaction conditions, short reaction time, high conversion, biocompatibility, and preservation of protein integrity. This review is organized based on the chemoselectivity and site-selectivity of the chemical bioconjugation reagents to the amino acid residues aiming to provide guidance for the selection of appropriate bioconjugation methods.

Isoindolium-Based Allenes: Reactivity Studies and Applications in Fluorescence Temperature Sensing and Cysteine Bioconjugation.

The reaction of a series of electron-deficient isoindolium-based allenes with sulfhydryl compounds has been studied, leading to the formation of isoindolium-based vinyl sulfides. The vinyl sulfides generated could be readily converted into the corresponding indanones and amines upon heating at 30-70 °C with good yields up to 61 %. The thermal cleavage reaction of vinyl sulfides was further studied for developing temperature-sensitive systems. Notably, a novel FRET-based fluorescent temperature sensor was designed and synthesized for temperature sensing at 50 °C, giving a 6.5-fold blue fluorescence enhancement. Moreover, chemoselective bioconjugation of cysteine-containing peptides with the isoindolium-based allenes for the construction of multifunctional peptide bioconjugates was investigated. Thermal cleavage of isoindoliums on the modified peptides at 35-70 °C gave indanone bioconjugates with up to >99 % conversion. These results indicated the biocompatibility of this novel temperature-sensitive reaction.

Perspective of smokers and healthcare professionals toward real-time video counseling smoking cessation program in general out-patient clinics in Hong Kong: a qualitative study.

OBJECTIVE: This study aimed to explore the perceptions and experiences of individuals that currently smoke and healthcare professionals on using real-time video counseling in the Smoking Cessation and Counselling Program in General Out-patient Clinics in Hong Kong. DESIGN: This was a qualitative study using face-to-face semi-structured interviews based on the extended technology acceptance model. All interviews were audiotaped and transcribed verbatim. Two investigators coded the transcripts independently. Thematic analysis was adopted. PARTICIPANTS: Individuals that currently smoke and healthcare professionals who had experience using real-time video counseling in the Smoking Cessation and Counselling Program in General Out-patient Clinics in Hong Kong were recruited. Purposive sampling was adopted. 18 participants were interviewed to reach data saturation. MAIN OUTCOME MEASURES: Themes that emerged from thematic analysis of data were the main outcome measures. The emerged themes were refined and verified via inductive and then deductive processes until data saturation was reached. RESULTS: Two core themes, which were in coherence with the extended technology acceptance model, namely (i) perceived ease of use and (ii) perceived usefulness, were identified. Under perceived ease of use, we identified 2 subthemes: (i) convenience and (ii) measures to facilitate the use of real-time video counseling. Three subthemes were identified under perceived usefulness: (i) empathy and rapport, (ii) measures for pandemics, and (iii) service outcome. CONCLUSION: Our study provided a culture-specific perspective of users towards real-time video counseling. It identified users' opinions on the easiness and usefulness of the service. Those could provide clues for future improvement and development of using real-time video counseling in healthcare services.

Effect of a patient education video and prehabilitation on the quality of preoperative person-centred coordinated care experience: protocol for a randomised controlled trial.

INTRODUCTION: Multimodal prehabilitation, an emerging field within the Perioperative Medicine specialty, requires close multidisciplinary team coordination. The goal is to optimise the patient's health status in the 4-8 weeks before elective surgery to withstand surgical stress. Most patients are unfamiliar with the concept of prehabilitation but are interested in participating in such a programme after explanation. The objective of this randomised controlled trial is to evaluate the effect of prehabilitation (patient education video and multimodal prehabilitation) on the preoperative patient-centred coordinated care experience. METHOD AND ANALYSIS: One hundred patients undergoing major elective surgery (cardiac, colorectal, hepatobiliary-pancreatic and urology) will be recruited into a two-group, parallel, superiority, single-blinded randomised controlled trial. Patients will be randomised to receive either preoperative patient education comprising of a video and prehabilitation programme with standard care (intervention) or standard care (control). The primary outcome measure will be the quality of preoperative patient care experience using the 11-item Chinese version of the Person-Centred Coordinated Care Experience Questionnaire (P3CEQ) before surgery. Secondary outcomes will include the change in Hospital Anxiety and Depression Scale (HADS) score from trial enrolment to before surgery, Quality of Recovery Score (QoR-15) on third day after surgery and Days Alive and At Home within 30 days after surgery (DAH30). Intention-to-treat and per-protocol analyses will be performed. ETHICS AND DISSEMINATION: The Joint CUHK-NTEC Clinical Research Ethics Committee approved the study protocol (CREC Ref. No. 2021.518-T). The findings will be presented at scientific meetings, in peer-reviewed journals and to study participants. TRIAL REGISTRATION NUMBER: ChiCTR2100053637.

Fluorogenic Protein Labeling by Generation of Fluorescent Quinoliziniums Using [Cp*RhCl2]2.

Fluorogenic labeling has received considerable attention as a result of the high demand in chemical biology and synthetic biology applications. Herein, we develop a new strategy for fluorescent turn-on ligation targeting alkyne- and quinoline-linked peptides and proteins (λem of 515 nm and up to ΦF of 0.20) using the [Cp*RhCl2]2 catalyst. The good conversion, high flexibility, broad utility, ease of use, and mild reaction conditions are great advantages to extend the rhodium-mediated turn-on fluorogenic bioconjugation for further applications.