We report the use of bioorthogonal reactions as an original strategy in photodynamic therapyt oa chieve conditional phototoxicity and specific subcellular localization simultaneously.O ur novel halogenated BODIPY-tetrazine probes only become efficient photosensitizers (F D % 0.50) through an intracellular inverse-electron-demand Diels-Alder reaction with as uitable dienophile.A binitio computations reveal an activation-dependent change in decaychannels that controls 1 O 2 generation. Our bioorthogonal approach also enables spatial control. As aproof-of-concept, we demonstrate the feasibility of the selective activation of our dormant photosensitizer in cellular nuclei, causing cancer cell death upon irradiation. Thus,o ur dual biorthogonal, activatable photosensitizers open new venues to combat current limitations of photodynamic therapy.Photodynamic therapy (PDT) is aw ell-established medical treatment for several maladies [1] that is based on the direct or indirect generation of cytotoxic reactive oxygen species (ROS) under exposure of ap hotosensitizer (PS) to light. [2] Light-controlled treatments,s uch as PDT,s hould overcome the medicinal challenge of side effects.However,the reality is that classical PSs have dark toxicity and al ack of selectivity, which causes undesirable adverse effects.Optogenetics [3] and photopharmacology [4] hold the promise to solve off-target issues,a lthough, unlike PDT,t hey are not yet at the stage of clinical development. Therefore,t here is ac lear need for improved PS designs that increase selectivity and minimize collateral injury to healthy tissue.A long these lines,s everal groups have demonstrated the potential of second-generation PSs,w hose therapeutic properties had been improved by either controllable activation [5] or specific delivery of the PSs. [6] Herein, we envision at hird-generation of PSs that combine both modulation of singlet oxygen ( 1 O 2 )production and controlled localization through ab ioorthogonal inverse-electron-demand Diels-Alder (iEDDA) tetrazine cycloaddition reaction.Since the discovery of the suitability of tetrazines for the bioorthoonal ligation pool in 2008, [7] this approach has become ap owerful bioconjugation method for imaging, [8] detection, [9] diagnostics, [10] and bioorthogonal release reactions. [11] However, its potential has not yet been exploited in PDT.Indeed, to the best of our knowledge,n one of the bioorthogonal reactions has ad irect application in the modulation of ROSproduction. Therefore,taking advantage of such ar eaction and inspired by the pioneering work of Weissleder and co-workers on superbright bioorthogonal boron dipyrromethene (BODIPY)/tetrazine turn-on probes, [12] we explore novel bioorthogonal turn-on probes for the controllable generation of 1 O 2 from the straightforward functionalization of the 4,4-difluoro-4-bora-3a,4a-diazas-indacene core. [13] BODIPY-based PSs have excellent photophysical properties, [14] and the quantum yield of their triplet excited state could be enhanced by the incorporation of ...

Phycobiliprotein is a light-harvesting complex containing linear tetrapyrrole bilin pigments that are responsible for absorption and funneling the sun’s energy in cryptophytes algae. In particular, the protein structure determines relative positions and orientations of the pigments and thus controls energy transfer pathways. The present research reveals the impact of molecular vibrations (in the 850–2700 cm−1 region) on excitation energy transfer in phycobiliprotein. The analysis of the excitation energy transfer pathways indicates a possibility of the coherent mechanism of energy transfer (delocalization) in central dihydrobiliverdin pigments and incoherent vibration-assisted energy transfer to peripheral phycocyanobilin pigments at a sub-picosecond time scale. A computational approach that enables modeling the dynamics of the excitation energy transfer with the quantum master equation formalism employing Huang-Rhys factors to describe electronic-vibrational coupling has been developed. The computational methodology has been implemented in PyFREC software.

A novel technology that employs computer vision (CV) to carry out an automatic titration experiment is presented. The experiment is designed to facilitate understanding of the basics of the CV technology and its application in chemistry among undergraduate students. The standard chemical procedure of titration has been chosen, since it is well-known to students who completed general chemistry or similar foundation chemistry courses. A significant advantage of CV-based automation is the use of open-source software and readily available electronic devices, as no expensive specialized equipment or proprietary software is required. The experiment can be performed remotely, either live online or with prerecorded videos. The reported technology is accessible to virtually any educational institution as well as to individuals. The proposed technology provides affordable and safe means for remote execution of titration experiments for students with disabilities. Therefore, the proposed experiment is suitable for traditional laboratory instruction as well as remote synchronous or asynchronous course delivery which gained practical importance during the COVID-19 pandemic. Finally, the proposed CV-based automation opens a new realm of opportunities for rethinking traditional chemistry procedures where computer vision is used to improve performance of standard laboratory instruments and techniques.

Wirb erichten über die Verwendung von bioorthogonalen Reaktionen als innovative Strategie in der photodynamischen Therapie,u mg leichzeitig eine gezielte Phototoxizitätu nd eine spezifisches ubzelluläre Lokalisation zu erreichen. Unsere neuartigen halogenierten BODIPY-Tetrazin-Sonden werden in Gegenwart eines geeigneten Dienophils über eine intrazelluläre Diels-Alder-Reaktion mit inversem Elektronenbedarf zu effizienten Photosensibilisatoren (F D % 0.50). Ab-initio-Berechnungen zeigen eine aktivierungsabhängige ¾nderung der Zerfallskanäle,d ie die 1 O 2 -Erzeugung steuern. Unser bioorthogonaler Ansatz ermçglicht weiterhin eine räumlicheK ontrolle.Als Proof-of-Concept demonstrieren wir hier die Mçglichkeit einer selektiven Aktivierung unseres ruhenden Photosensibilisators im Zellkern, der dann bei Bestrahlung zum Absterben von Krebszellenf ührt. So erçffnen unsere dualen bioorthogonal aktivierbaren Photosensibilisatoren neue Mçglichkeiten, um die gegenwärtigen Begrenzungen der photodynamischen Therapie zu überwinden.

Excitation energy transfer is a ubiquitous process of fundamental importance for understanding natural phenomena, such as photosynthesis, as well as advancing technologies ranging from photovoltaics to development of photosensitizers and fluorescent probes used to explore molecular interactions inside living cells. The current version of PyFREC 2.0 is an advancement of the previously reported software (D. Kosenkov, J. Comput. Chem. 2016, 37, 1847–1854). The current update is primarily focused on providing a computational tool based on Förster theory for bridging a gap between theoretically calculated molecular properties (e.g., electronic couplings, orientation factors, etc.) and experimentally measured emission and absorption spectra of molecules. The software is aimed to facilitate deeper understanding of photochemical mechanisms of fluorescence resonance energy transfer (FRET) in donor–acceptor pairs. Specific updates of the software include implementations of overlap integrals between donor emission and acceptor absorption spectra of FRET pairs, estimation of Strickler–Berg fluorescence lifetimes, calculation of Förster radii, energy transfer efficiency, and radiation zones that, in particular, determine applicability of the Förster theory.