Institute of Organic Synthesis and Photoreactivity

Multifunctional silk fibroin (SF) nanofibrous membranes incorporating cuttlefish ink (CI) and vitamin B2 (VitB2) were developed via water-based electrospinning as bioactive scaffolds for soft tissue regeneration and laser-assisted tissue welding. CI provided antioxidant and photothermal properties, while VitB2 promoted cellular proliferation. Membranes exhibited controlled VitB2 release and CI retention within the matrix. NIH-3T3 fibroblast assays confirmed high viability (>80% at 48 h), with CI promoting adhesion and cytoskeletal organization, and VitB2 enabling formation of a confluent, organized cell layer. Laser-assisted welding produced satisfactory adhesion and shear-stress resistance on the order of ten kPa in ex vivo tendons, corneas, and sclerae, while keeping tissue temperatures below the 60 °C threshold for thermal damage. These findings highlight CI- and VitB2-loaded SF membranes as sustainable, cytocompatible scaffolds with antioxidant and adhesive functionalities, offering a versatile platform for soft tissue repair via an adhesive-free approach.

Effective decoupling between donors and the acceptor in V-shaped D–π–A–π–D molecules enables the excited-state landscape to be governed almost entirely by the intrinsic donor strength, which dictates fluorescence, TADF, and singlet-oxygen generation.

Two tert -butyl groups on the phenyl moiety affords a suitable steric hindrance to boost the external quantum efficiency whereas the introduction of methyls ortho to the interannular C–C bond switches the colour from “emerald green” to “sky-blue”.

Marine biotechnology is an emerging field of research. There is scientific evidence of the strong potential of a multitude of marine microorganisms in biotechnology, with applications spanning the medical, pharmaceutical, cosmeceutical, nutraceutical and environmental recovery fields. However, despite the discovery of new natural compounds being of wide-ranging benefit, their practical application still remains difficult due to costs and lengthy validation processes. The strength of natural compounds is that, unlike synthetic or already-known compounds, they can have more specific functions and are generally environmentally friendly. This requires, however, that each newly discovered compound be assayed for its toxicity through tests on model cells and organisms. Research should therefore not stop with the simple discovery of new compounds but go beyond with the validation of their efficacy and safety, an issue that remains poorly addressed for products of marine bacterial origin. This review analyses current knowledge on natural compounds of marine bacterial origin, trying to focus on the necessary steps after their discovery, including the investigation of their non-toxicity to model organisms.

Metallo-β-lactamases(MBL) production is one of the mostalarming bacterial resistance mechanisms, conferring broad-spectrumresistance to most β-lactam antibiotics and combinations withβ-lactamase inhibitors. Since no MBL inhibitors have been approvedyet, the quest for novel, safe, and effective compounds, possiblyendowed with broad-spectrum activity against clinically relevant MBLs,represents an urgent clinical need. Inspired by captopril, which behavesas a weak MBL inhibitor, we herein report a continuous flow protocolfor the generation of new MBL inhibitors. We employed a Joullié–Ugimulticomponent reaction for generating two indoline-based subseries,reproducing the captopril binding mode, while increasing the hydrophobicinteractions within the MBL active site. Interaction between inhibitorsand five clinically relevant MBL isoforms (NDM-1, VIM-1, VIM-2, IMP-1,and IMP-7) was investigated by biochemical methods and rationalizedthrough docking studies. Furthermore, the activity in clinical isolatesin synergy with β-lactam antibiotics was assessed, thus pavingthe way to a further optimization campaign.

For decades, progress in chiral transition metal catalysis has been closely linked to the design of tailor-made chiral ligands. Recently, an alternative to this conventional paradigm has emerged in which the overall chirality of the catalysts arises solely from a stereogenic metal center. However, the development of such chiral-at-metal catalysts based on earth-abundant metals is still a formidable challenge. Here, we report a reactive chiral-at-cobalt catalyst comprised entirely of achiral ligands, more than a century after Alfred Werner first introduced chiral cobalt complexes with exclusive metal-centered chirality. The cobalt center uniquely serves multiple functions: it is the sole stereocenter, redox center, catalytic site, and a chromophore. While the cobalt(III) complex is inert and bench-stable under ambient conditions, it can be photoactivated through an unexpected counterion-assisted mechanism, reducing inert cobalt(III) to catalytically active cobalt(II). This chiral-at-cobalt complex enables the visible-light-activated enantioselective conversion of isoxazoles into chiral 2H-azirines, achieving high enantiomeric excess of up to 97%.

Cardiovascular diseases are responsible for a large number of severe disability cases and deaths worldwide. Strong research in this field has been extensively carried out, in particular for the associated complications, such as the occlusion of small-diameter (<6 mm) vessels. Accordingly, in the present research, two random copolyesters of poly(butylene 2,5-furandicarboxylate) (PBF) and poly(butylene isophthalate) (PBI), were successfully synthesized via two-step melt polycondensation and were thoroughly characterized from molecular, thermal, and mechanical perspectives. The copolymeric films displayed a peculiar thermal behavior, being easily processable in the form of films, although amorphous, with Tg close to room temperature. Their thermal stability was high in all cases, and from the mechanical point of view, the materials exhibited a high ultimate strength, together with values of elastic moduli tunable with the chemical composition. The long-term stability of these materials under physiological conditions was also demonstrated. Cytotoxicity was assessed using a direct contact assay with human umbilical vein endothelial cells (HUVECs). In addition, hemocompatibility was tested by evaluating the adhesion of blood components (such as the adsorption of human platelets and fibrinogen). As a result, a proper chemical design and, in turn, both the solid-state and functional properties, are pivotal in regulating cell behavior and opening new frontiers in the tissue engineering of soft tissues, including vascular tissues.

Retinoblastoma (Rb) is a rare cancer, yet it is the most common eye tumor in children. It can occur in either a familial or sporadic form, with the sporadic variant being more prevalent, though its downstream effects on epigenetic markers remain largely unclear. Currently, the treatment for retinoblastoma typically involves aggressive chemotherapy and surgical resection. The identification of specific epigenetic characteristics of non-hereditary (sporadic) Rb has led to the development of advanced, high-throughput methods to explore its epigenetic profile. Our previous research demonstrated that treatment with the demethylating agent 5-Aza-2'-deoxycytidine (decitabine; DAC) induced cell cycle arrest and apoptosis in a well-characterized retinoblastoma model (WERI-Rb-1). Our analysis of time-dependent gene expression in WERI-Rb-1 cells following DAC exposure has led to the development of testable hypotheses to further investigate the epigenetic impact on the initiation and progression of retinoblastoma tumors. Gene expression analysis of publicly available datasets from patients' primary tumors and normal retina have been compared with those found in WERI-Rb-1 cells to assess the relevance of DAC-driven genes as markers of primary retinoblastoma tumors. The effect of DAC treatment has been evaluated in vivo, both in subcutaneous xenografts and in orthotopic models. qPCR analysis of gene expression and Methylation-Specific PCR (MSP) was performed. Our analysis of network maps for differentially expressed genes in primary tumors compared to DAC-driven genes identified 15 hub/driver genes that may play a pivotal role in the genesis and progression of retinoblastoma. DAC treatment induced significant tumor growth arrest in vivo in both subcutaneous and orthotopic xenograft retinoblastoma models. This was associated with changes in gene expression, either through the direct switching-on of epigenetically locked genes or through the indirect regulation of linked genes, suggesting the potential use of DAC as an epigenetic anti-cancer drug for the treatment of retinoblastoma patients. There is a pressing need to develop innovative treatments for retinoblastoma. Our research revealed that DAC can effectively suppress the growth and progression of retinoblastoma in in vivo models, offering a potential new therapeutic approach to battle this destructive disease. This discovery highlights the impact of this epigenetic therapy in reprogramming tumor dynamics, and thus its potential to preserve both the vision and lives of affected children.

Within the framework of rational drug design, this study introduces a novel approach to enhance the specificity of small molecules in targeting cancer cells. This approach starts from the use of dyads merging into a single entity, a naphthalene diimide (NDI) and core-extended NDI (ceNDI), both known as G-quadruplex (G4) ligands and fluorescent probes. The strategy aims to leverage the unique diagnostic strengths of the ceNDI moiety featuring red emission by improving its binding affinity and target selectivity through inclusion in dyads built with different linkers. The newly developed NDI-ceNDI dyads are promising probes, as they exhibit fluorescence turn-on upon DNA recognition and induced circular dichroism signals dependent on DNA conformation. Both dyads have an excellent affinity for hybrid G4, with two orders of magnitude higher binding constants than those for ds DNA. Their high cytotoxicity on cancer cell lines further demonstrates their potential as therapeutic agents, highlighting the role of the linker in target selectivity. Specifically, only the dyad with the rigid triazole linker exhibits selectively induced DNA damage in transformed cells, compared to normal cells primarily targeting telomeric regions. Our findings shed light on DIPAC's potential as a promising theranostic agent, offering insights into future developments in precision medicine.