New tactics in the design of theranostic radiotracers.

In the context of molecularly targeted radiotherapy, dosimetry concerns in off-target tissues are a major limitation to the more wide-spread application of radiopharmaceuticals to treat diseases like cancer. Reducing off-target accumulation of radionuclides in background tissues, whilst maintaining high and specific uptake in disease sites and improving the therapeutic window, requires rethinking common radiotracer design concepts. This article explores ways in which innovative radiotracer chemistry (the making and breaking of bonds) is used to modify interactions with the host organism to control excretion profiles and dosimetry at the tissue-specific level.

Light-Induced Synthesis and Radiotheranostic Treatment of Gastric Cancer with Tb-Labeled Monoclonal Antibodies.

Radiolabeled monoclonal antibodies (mAbs) form a major branch of nuclear medicine and are used in the development of tracers for both diagnostic imaging and molecularly targeted radio-(immuno)-therapy (RIT). Since treatment options for many types of late-stage cancers are limited and these diseases become refractory to classic chemotherapy, new tools are required to improve patient outcomes. The high tumor uptake and specificity of mAbs, coupled with increased therapeutic range of energetic β-emitting radionuclides, offers a potential solution to overcome traditional problems associated with poor tissue penetration of antibody-drug conjugates, chemotherapeutic resistance, and off-target accumulation, which can lead to adverse responses.

Photoradiolabeling of onartuzumab with Tc and Re-tricarbonyl for radiotheranostics of gastric cancer.

The clinically relevant nuclear isomer of technetium-99 (Tc) and the radionuclides rhenium-186/188 (Re and Re) represent an almost ideal match for the development of radiotracers for applications in diagnostic imaging and molecularly targeted radionuclide therapy. Although the chemistry of Tc and Re is similar, important differences arise in both the synthesis and properties of their complexes. Here, we report the synthesis and characterization of Tc- and Re-onartuzumab by labeling of the cancer-specific mAb onartuzumab (MetMAb) with the corresponding metal-tricarbonyl complexes derived from a novel photoactivatable ligand.

Light-induced chemistry for protein functionalisation.

Derivatising biomolecules like monoclonal antibodies with drugs or imaging agents, whilst preserving their bioactivity, is a challenging task. Protein functionalisation ideally requires methods that operate under mild conditions, are rapid, efficient (high yielding), chemoselective or site-specific, and importantly, non-denaturing. A broad collection of thermally mediated reagents for direct labelling using protein-based reactivity, or bioorthogonal strategies, has been developed, but arguably the most exciting opportunities lie in the application of photochemistry to create new covalent bioconjugate bonds.

Wiring proton gradients for energy conversion.

Light-switchable buffer solutions based on merocyanine photoacids can be used as efficient photoenergy harvesting systems. Varying the solvation environment of merocyanine photoacids in water-methanol mixtures allows one to carefully tune their photoacidity, relaxation kinetics, and solubility, opening up the possibility to install persistent pH gradients of approximately 4 pH units under 500 nm light. When interfaced between two electrodes and exposed to asymmetric light irradiation, these solutions can be photoactivated precisely both in space and time, generating open circuit voltages as high as 240 mV that can last hours under steady-state irradiation - an outcome that is akin the peak performance of biological transmembrane proton pumps.

Controlling DNA nanodevices with light-switchable buffers.

Control over synthetic DNA-based nanodevices can be achieved with a variety of physical and chemical stimuli. Actuation with light, however, is as advantageous as difficult to implement without modifying DNA strands with photo-switchable groups. Herein, we show that DNA nanodevices can be controlled using visible light in photo-switchable aqueous buffer solutions in a reversible and highly programmable fashion.

Synthetic Receptors with Micromolar Affinity for Chloride in Water.

A water-soluble coordination cage was obtained by reaction of Pd(NO ) with a 1,3-di(pyridin-3-yl)benzene ligand featuring a short PEG chain. The cavity of the metal-organic cage contains one nitrate anion, which is readily replaced by chloride. The apparent association constant for chloride binding in buffered aqueous solution is K =1.

A Mesoionic Diselenolene Anion and the Corresponding Radical Dianion.

Dichalcogenolenes are archetypal redox non-innocent ligands with numerous applications. Herein, a diselenolene ligand with fundamentally different electronic properties is described. A mesoionic diselenolene was prepared by selenation of a C2-protected imidazolium salt.

Light-Switchable Buffers.

A visible light-switchable buffer system based on a merocyanine photoacid is presented. Para-substitution of the indolium side with a methoxy group affords a compound suitable for making hydrolytically stable aqueous buffers whose pH can be tuned between 7 and 4 using 500 nm light.

Correction: Light-induced assembly and disassembly of polymers with Pd L -type network junctions.

[This corrects the article DOI: 10.1039/D1SC00127B.].

Light-induced assembly and disassembly of polymers with Pd L -type network junctions.

Polymers containing Pd L complexes as network junctions were obtained by reaction of poly(ethylene glycol)-linked N-donor ligands with Pd. The addition of a metastable state photoacid renders the networks light sensitive, and gel-sol transitions can be achieved by irradiation with light. The inverse process, a light-induced sol-gel transition, was realized by using a molecularly defined Pd complex as an acid-sensitive reservoir for Pd.

Thermodynamics and kinetics of protonated merocyanine photoacids in water.

Metastable-state photoacids (mPAHs) are chemical species whose photo-activated state is long-lived enough to allow for proton diffusion. Liao's photoacid () represents the archetype of mPAHs, and is being widely used on account of its unique capability to change the acidity of aqueous solutions reversibly. The behavior of in water, however, still remains poorly understood.