Cassandra Lee Fleming

The burgeoning reliance on fluorescence techniques to detect analytes of interest and visualize cellular processes has heightened the need for synthetic approaches to readily access new and underrepresented fluorophore classes, including those based on the 2,3‐naphthalimide scaffold. To address the lack of robust synthetic methodology, a general route to access structurally diverse fluorescent 2,3‐naphthalimides has been developed. Following the synthesis of the key 6‐bromo‐2,3‐naphthalic anhydride building block, imide formation and subsequent amination via Buchwald–Hartwig cross‐coupling methodology afforded a number of 6‐aminonaphthalimides with solvatochromic properties. Microscopy experiments in A549 cells highlight their potential as fluorescent probes for bio‐relevant imaging, with a 6‐piperazino‐2,3‐naphthalimide variant demonstrating pH‐responsive fluorescent behavior via photoinduced electron transfer.

The utilisation of light as an external stimulus to control the structure and function of bio-relevant molecules in healthy and diseased cells and tissues serves as a valuable means to probe fundamental molecular events of complex cellular processes. Indeed, the photocaging approach has proved highly popular, whereby bioactive molecules are modified with photolabile protecting groups, rendering them temporarily inactive. Biological activity is only restored upon irradiation with a defined wavelength of light, resulting in the irreversible cleavage of the caging group. While seminal works are reliant on the use of phototoxic UV light for photoactivation, the rapid evolution of the field of photopharmacology has facilitated the development of more sophisticated caging groups with physiochemical and photophysical properties better suited for in vivo applications. Herein, we highlight the recent progress made on the development of BODIPY-, cyanine- and xanthene-derived caging groups, which utilise visible-to-near-infrared light for photoactivation. The strategies employed to red-shift absorption spectra, as well as improve photolysis efficiencies and aqueous solubility have been of particular interest, and are therefore discussed in detail in this review.

The syntheses of the tripodal tetraamine ligands 2‐(pyridin‐2‐yl)‐N,N‐bis(quinolin‐2‐ylmethyl)ethan‐1‐amine (DQPEA), N‐(pyridin‐2‐ylmethyl)‐2‐(quinolin‐2‐yl)‐N‐(2‐(quinolin‐2‐yl)ethyl)ethan‐1‐amine (DQEPMA), 2‐(pyridin‐2‐yl)‐N,N‐bis(2‐(quinolin‐2‐yl)ethyl)ethan‐1‐amine (DQEPEA), N,N‐bis(pyridin‐2‐ylmethyl)‐2‐(quinolin‐2‐yl)ethan‐1‐amine (QEDPMA), and 2‐(pyridin‐2‐yl)‐N‐(2‐(pyridin‐2‐yl)ethyl)‐N‐(2‐(quinolin‐2‐yl)ethyl)ethan‐1‐amine (QEDPEA) containing mixed quinolyl and pyridyl moieties are reported, with 2‐vinylquinoline being used to attach quinolylethyl arms to the aliphatic N atom. X‐ray crystal structures of [(Mn(DQPEA))₂O₂](ClO₄)₂ ⋅ (CH₃CN)₂, [Cu(DQPEA)NCCH₃](ClO₄)₂, [Zn(DQPEA)NCCH₃](ClO₄)₂, [Pd(DQEPEA)Cl]Cl ⋅ 11H₂O are detailed, with four, five, and six‐coordination observed. In addition, the dimeric complex [(DPEA)Co(μ‐OH)₃Co(DPEA)](ClO₄)₃ ⋅ 0.5H₂O ⋅ MeCN containing the tridentate DPEA ligand formed by N‐dealkylation of QEDPEA is reported. Calculations suggest that the very short Co…Co distance of 2.5946(6) Å in this complex is unlikely to be due to a Co−Co bond.

The development of light‐responsive molecular tools enables spatiotemporal control of biochemical processes with superior precision. Amongst these molecular tools, photolabile caging groups are employed to prevent critical binding interactions between a bioactive molecule and its corresponding target. Only upon irradiation with light, the bioactive is released in its ‘active’ form and is now readily available to bind to its target. Coumarin‐derived caging groups constitute one of the most popular classes of photolabile protecting groups, due to their facile synthetic accessibility, ease of tuning photophysical properties via structural modification and rapid photolysis reactions. Herein, we highlight the recent progress made on the development of coumarin‐derived caging groups, in which the red‐shifting of absorption spectra, improving aqueous solubility and tailoring sub‐cellular localisation has been of particular interest.

The carbene carbon of the multidentate ligand PY4Im induces a consistent trans influence in a number of Co(iii) complexes.

An all-photonic method is described, in which (i) the release of an active kinase inhibitor is controlled externally with light; and (ii) fluorescence is employed to report both the release and binding of the inhibitor to its corresponding target.

The development of new and effective therapeutics is reliant on the ability to study the underlying mechanisms of potential drug targets in live cells and multicellular systems. A persistent challenge in many drug development programmes is poor selectivity, which can obscure the mechanisms involved and lead to poorly understood modes of action. In efforts to improve our understanding of these complex processes, small molecule inhibitors have been developed in which their OFF/ON therapeutic activity can be toggled using light. Photopharmacology is devoted to using light to modulate drugs. Herein, we highlight the recent progress made towards the development of light‐responsive small molecule inhibitors of selected enzymatic targets. Given the size of this field, literature from 2015 onwards has been reviewed.

The development of a fluorescent LCK inhibitor that exhibits favourable solvatochromic properties upon binding the kinase is described. Fluorescent properties were realised through the inclusion of a prodan‐derived fluorophore into the pharmacophore of an ATP‐competitive kinase inhibitor. Fluorescence titration experiments demonstrate the solvatochromic properties of the inhibitor, in which dramatic increase in emission intensity and hypsochromic shift in emission maxima are clearly observed upon binding LCK. Microscopy experiments in cellular contexts together with flow cytometry show that the fluorescence intensity of the inhibitor correlates with the LCK concentration. Furthermore, multiphoton microscopy experiments demonstrate both the rapid cellular uptake of the inhibitor and that the two‐photon cross section of the inhibitor is amenable for excitation at 700 nm.