Synthesis of boron dipyrromethene fluorescent probes for bioorthogonal labeling

Abstract

Seven 5-substituted 3-hydrazinyl derivatives of 3a, 4a-diaza-4,4-difluoro-8-phenyl boron dipyrromethene (BODIPY) were prepared for use as bioorthogonal fluorescent labels of aldehydes and ketones. The absorption energies can be tuned to absorb visible light over a large span of wavelengths by changing the nature of the 5-substituent. Optical properties of the hydrazones formed with these molecules are affected by the nature of the electrophile such that aliphatic and aromatic hydrazones can be differentiated from each other and from unreacted fluorophore.

Figure 2.

Normalized absorption spectra of some compounds in ethanol. From left to right: 7 (cyan), 4 (pink), 2 (black), 8 (dark green),1(red),3(purple).

Figure 3.

Solutions of 2, 9 and 10 in dichloromethane under room light (left) and long wavelength fluorescent light (right).

Figure 4.

Normalized fluorescence emission spectra 2, 9 and 10. From left to right, parent hydrazine 2 (black, λ_ex= 478 nm), aliphatic hydrazone 9 (red, λ_ex= 513 nm), aromatic hydrazone 10 (blue, λ_ex= 531 nm).

Scheme 1.

Structures of BDPs 1-8

Scheme 2.

Structures of hydrazones of 2