Study of Photochemistry and Mechanisms of Photoactivatable Compounds

Dominik Madea,^1) Jiří Janoš,^2) Taufiqueahmed Mujawar,^1) Marek Martínek,^1) Aleš Dvořák,^3) Lucie
     Muchová,^3) Petra Čubáková,^4^) Miroslav Kloz,^4^) Petr Slavíček,^2) Jiří Váňa,^5^) Jakub
                              Švenda,^1) Libor Vítek,^3) Petr Klán^1)

                                                 ^

^1) Department of Chemistry and RECETOX, Faculty of Science, Masaryk University, Kamenice 5/A8, 625
    00 Brno, Czech Republic. ^2) Department of Physical Chemistry, University of Chemistry and
                     Technology, Technická 5, 16628 Prague 6, Czech Republic.

^3) Institute of Medical Biochemistry and Laboratory Diagnostics, 1^st Faculty of Medicine, Charles
  University, Na Bojišti 3, 121 08 Praha 2, Czech Republic.^ 4) Institute of Physics of the Czech
  Academy of Sciences, ELI Beamlines, Za Radnicí 835, 252 41 Dolní Břežany, Czech Republic.^ ^5)
   Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of
                    Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic


The work consist of two separate projects. In the first project, synthesis, optical properties and
study of the sensing mechanism of Nile-red Pd-based carbon monoxide (CO) chemosensors,[1]
structurally modified by core and bridge substituents, in methanol and aqueous solutions are
reported. CO is a cell-signaling molecule (gasotransmitter)[2] produced endogenously by oxidative
catabolism of heme, and its spatial and temporal sensing at the cellular level is still an open
challenge.[3] The fluorescence of the “off-on” palladacycle-based sensors arises from their
reaction with CO to release the corresponding highly fluorescent Nile red derivatives in the final
step. Our kinetic study showed that electron-withdrawing and electron-donating core substituents
affect a rate-determining step of the reaction. More importantly, the substituents were found to
have a substantial effect on the Nile red sensor fluorescence quantum yields, hereby defining the
sensing detection limit. The highest overall fluorescence and sensing rate enhancements were found
for a 2-hydroxy palladacycle derivative, which was used in subsequent biological studies on mouse
hepatoma cells as it easily crosses the cell membrane and qualitatively traces localization of CO
within the intracellular compartment with the linear quantitative response to increasing CO
concentrations.[4]

In the second project, the photochemistry of bilirubin (BR) dipyrrinone subunits (1 and 2, prepared
as the corresponding methyl esters) were studied by steady-state and transient
spectroscopies.[5,6,7] Bilirubin is an essential metabolite formed by the catabolism of heme.
Phototherapy with blue-green light can be applied to reduce high concentrations of BR in blood,
especially in the neonatal period.[8] Bilirubin subunits represent useful models to study the
complex photochemistry of bilirubin. Both subunits undergo efficient reversible photoisomerization
(Φ[ZE] ~ Φ[EZ] ~ 0.15–0.30), furthermore, E-1 undergo lumirubin-type photorearrangement to form a
seven-membered ring system. The cyclization process is significantly less efficient (Φ[c] ~
0.001–0.07), but is strongly wavelength-dependent. The photochemistry of bilirubin dipyrrinone
subunits and its biological properties are discussed and compared to those of bilirubin.



[1] Liu, K. Y.; Kong, X. Q.; Ma, Y. Y.; Lin, W. Y. Angew. Chem. Int. Ed. 2017, 56, 13489-13492.

[2] Ryter, S. W.; Alam, J.; Choi, A. M. K. Physiol. Rev. 2006, 86, 583-650.

[3] Wu, L.; Wang, R. Pharmacol. Rev. 2005, 57, 585-630.

[4] Madea, D.; Martínek, M.; Muchová, L.; Vítek, L.; Klán, P.  J. Org. Chem. 2020, 85, 3473-3489.

[5] Madea, D. et. al. J. Org. Chem. 2020, 85, 13015.

[6] Janoš, J.; Madea, D. et. al. J. Phys. Chem. A. 2020, 124, 10457.

[7] Madea, D. et. al. (submitted to J. Org. Chem.)

[8] Vítek, L.; Ostrow, J. D. Curr. Pharm. Des. 2009, 15, 2869.