Access to 2,6-Dipropargylated BODIPYs as “Clickable” Congeners of Pyrromethene-567 Dye: Photostability and Synthetic Versatility

Hitherto unreported 2,6-dipropargyl-1,3,5,7-tetramethyl BODIPYs can be efficiently prepared by a Nicholas reaction/decomplexation protocol from 1,3,5,7-tetramethyl BODIPYs. The title compounds, which improve the BODIPY photostability by retaining their inherent photophysical and photochemical properties, can be engaged in efficient copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) “click-type” reactions with azido derivatives to provide all-BODIPY-triads or conjugated BODIPYs.


General procedure A. Nicholas reaction of BODIPYs with dicobalt hexacarbonyl propargyl alcohol complex 5
A solution of the corresponding BODIPY (4, 7a-c) and dicobalt hexacarbonyl propargyl alcohol

General procedure B. Oxidative iodine-mediated decobaltation
A solution of the corresponding propargylcobalt-BODIPY (1 equiv.) in THF or CH2Cl2 was cooled to 0 °C, then solid iodine (3 equiv.) was added. The mixture was stirred under these conditions for 30-90 min, then poured into saturated aqueous NaHCO3 + 10% Na2S2O3 solution and partitioned twice with ether or CH2Cl2. The combined organic layers were washed once with brine, dried over MgSO4, and filtered, and the solvent was removed in vacuo. The crude material was purified through silicagel column chromatography.

General procedure C. Non-oxidative 1,2-ethylenediamine mediated decobaltation
A solution of the corresponding propargylcobalt-BODIPY (1 equiv.) in THF was treated with 1,2ethylenediamine (3 equiv.). The reaction mixture was stirred at room temperature until TLC showed complete disparition of the complex, then it was diluted with Et2O and washed with a 3% HCl solution and brine. The organic layer was dried over MgSO4 and concentrated. The residue was purified by silica column chromatography.
The resulting mixture was stirred and the reaction was followed by t.l.c.. The reaction mixture was then quenched with the addition of 1M NaOH. The combined organic extracts were dried over MgSO4, filtered and concentrated. The residue was then purified, if necessary, by silical gel chromatography. In most instances the starting BODIPY was recovered unchanged. In one of the ocassions (using BF3.OEt2 as Lewis acid) the dipropargyl derivative 10b could be isolated (37% yield).

Cholester-3b-yl 2-Azidoacetate
Compound 17a. Following the general procedure D, BODIPY 10b (52 mg, 0.13 mmol) and benzyl azide (38 µL, 0.31 mmol) in CH2Cl2 (6 mL) were added to a solution of sodium ascorbate ( Fluorescence emission was monitored at the maximum emission wavelength after excitation by S19 the said Fianium at the maximum absorption wavelengths. The fluorescence lifetime (t) was obtained from the slope of the exponential fit of the decay curve, after the deconvolution of the instrumental response signal (recorded by means of a ludox scattering suspension) by means of an iterative method. The goodness of the exponential fit was controlled by statistical parameters (chi-square and the analysis of the residuals). The radiative (kfl) and non-radiative (knr) rate constants were calculated from the fluorescence quantum yield and lifetime; kfl = f/t and knr = (1-f)/t.

Lasing properties
Laser efficiency was evaluated from concentrated solutions ( Information about photostabilitiy was obtained by monitoring the decrease in laser-induced fluorescence (LIF) intensity after 130 000 pump pulses and 10 Hz repetition rate to speed up the experimental running. Laser emission emissions was monitored perpendicular to the exciting beam, collected by an optical fiber, and imaged onto a spectrometer (Acton Research corporation) and detected with a charge-coupled device (CCD) (SpectruMM:GS128B). Laserinduced emission was monitored in front-face configuration and recorded by feeding the signal to the boxcar (Stanford Research, model 250) to be integrated before being digitized and processed by a computer. The estimated error in the energy and photostability measurements was 10%.

Computational chemistry
Ground state geometries were optimized with the b3lyp hybrid functional, within the Density Functional Theory (DFT), using the double valence basis set with a polarization function (6-31G*). The geometries were considered as energy minimum when the corresponding frequency analysis did not give any negative value. The absorption spectra was simulated as a Franck-Condon vertical transition from the optimized ground state geometries using the time dependent method with the aforementioned functional and basis set (td b3lyp/6-31g*). All the theoretical calculations were carried out using the GAUSSIAN 16 program suite, implemented in the computational cluster provided by the SGIker resources of UPV-EHU.
The corresponding data of the commercially available BODIPYs 2 (PM567) in ethyl acetate are also added for comparison (in italics).
The corresponding data of the isolated red-emitting fragment 19 are also added for comparison. a) Dye concentration: 2 µM. Absorption (lab) and fluorescence (lfl) wavelength, molar absorption (emax), fluorescence quantum yield (f) and lifetime (t). b) Dye concentrations in ethyl acetate ranging from 1´10 -4 M to 1´ 10 -3 M to match the optical density at the irradiation wavelengths (532nm and 355 nm). Laser wavelength (lla) and efficiency (%Eff). EtOAc: ethyl acetate; ACN: acetonitrile *these fluorescence and laser parameters remain the same regardless of the excited fragment