Triggering the release of chemical species through the use of light is crucial for modern microscopy applications, such as single‐molecule localization and, in general, in the regulation of molecular effectors. Herein, we demonstrate a nonlinear‐optical scheme for the control of photorelease. Our system consists of a two‐photon‐absorbing photoremovable protecting group (PPG) bonded to a second chromophore which undergoes photo‐induced detachment and activation upon excitation with λ=850 nm femtosecond pulses. The two‐photon PPG section consists of a cyanine‐type dye, and the releasable section is a highly fluorescent derivatized anthracene chromophore bonded to the cyanine through a photolabile etheric‐meso‐carbon bond. This method allows for the release of a fluorophore following a spatially localized two‐photon excitation event. Both the excitation energy and the long lifetime of the upper excited states of the PPG chromophore are thought to be involved in the release process.

A new molecular architecture was designed to amplify the sensitivity of bichromophoric probes, in which two sequential kinetic competitions of photophysical channels were used to define the emission yield of the lower energy chromophore. Additionally, the emission from both chromophores can be used for ratiometric measurements, which are concentration independent. Two sensors were synthesized to demonstrate the concept, coupling a boron-dipyrromethene (BODIPY) dye and a cyanine dye. Both the energy transfer from the BODIPY to the cyanine and the cyanine radiative channel compete with a charge transfer state formation, giving the cyanine emission intensity a twofold dependence on polarity. This was confirmed with steady state and time-resolved spectroscopies. Also, the large spectral gap between the two emissions (approx. 280 nm) makes the ratiometric measurements crosstalk-free. The use of the sensors in live cells was demonstrated through the staining and imaging of SK-LU-1 lung cells under normal and apoptotic conditions.[a] A.Changes in the microenvironment of these molecules will affect the kinetics of the last process, and thus, the yields of the three competing processes. The molecules that underwent the RET process will then have the excitation localized in the second chromophore. The polarity-dependent formation of the CT state in the second chromophore will compete with its locally excited emission. This double dependence on the polarity of the medium gives these systems an enhanced sensitivity to different solvent or cell environments.Two prototype molecules were synthesized to demonstrate these design principles (see Figure 1). This was achieved by coupling the commercially available IR780 cyanine with a BODIPY dye trough a bridge formed by an ether bond and two different aromatic moieties: a phenyl group (BBIR) or a naphthyl group (BNIR). The aromatic moieties were selected to analyse the effect of changing the electron donor in the formation of the CT states and the sensitivity of the sensors while maintaining the distances between the energy transfer donor and the acceptor. The precursor cyanine IR780 was chosen due to its optical properties and because it can be easily functionalized at the meso position. Additionally, the IR780 cyanine has been widely used as a near-IR fluorescent probe due to its low toxicity and facile uptake by cells and tissues. [22,23] The water-2 3 4 5 6 7 8

The front cover artwork is provided by members of the Instituto de Química at Universidad Nacional Autónoma de México (UNAM). The image represents a spatially localized photochemical cleavage induced by two‐photon absorption of NIR ultrashort laser pulses. A highly fluorescent species is formed in the process. Read the full text of the Article at 10.1002/cptc.201700076.

The Front Cover picture represents a two‐photon‐induced release event in a 3D spatially localized region. More information can be found in the Article by J. Peon and co‐workers on page 397 in Issue 9, 2017 (DOI: 10.1002/cptc.201700076).

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