Tuning the photophysical properties of luminescent lanthanide complexes through regioselective antenna fluorination †

Carbostyrils monofluorinated in the 3, 5, or 6 positions were synthesised from olefinic precursors via a photochemical isomerisation-cyclisation route, and incorporated into octadentate cyclen triacetate ligands that formed luminescent complexes with Tb( III ) and Eu( III ). The photophysical properties of the emitters were strongly dependent on the position of the fluorination.

The luminescence of the trivalent lanthanide (Ln) ions is applied in diverse biological and industrial settings ranging from the monitoring of the components of living cells to the thermometric analysis of materials. 1,2 Ln(III) luminescence is often sensitised by a light-harvesting antenna to avoid the need for direct excitation of the Laporte-forbidden 4f-4f transitions. 3 Optimisation of energy transfer (EnT) to the Ln(III) and elimination of processes that quench the antenna and Ln(III) excited states are essential for bright emitters.
Photoinduced electron transfer (PeT) from the excited antenna to Ln(III) is feasible for several Lns, 4,5 and for Eu(III) emission it can be an effective luminescence quenching process. 6 PeT is suppressed when the antenna is less reducing. Antenna substitution with electron-withdrawing groups (e.g. with CF 3 , Fig. 1) 4,5 or protonation 7,8 can increase the Eu(III) luminescence quantum yield, but may have unintended consequences on the antenna excited state energies. 5,9,10 Ln sensitisation commonly takes place via the antenna singlet (S 1 ) and triplet excited states (T 1 ). Even subtle changes to the antenna may alter the S 1 and T 1 energies and EnT. In the previous examples both antenna trifluoromethylation 4,5 and protonation proved detrimental to Tb(III) emission. 8 Here, we have prepared three monofluorinated 7aminocarbostyril regioisomers. Electronegative fluorine was expected to decrease PeT by making the antenna less reducing, a strategy that complements the use of C-F bonds to replace the more efficiently quenching C-H oscillators. 11 Fluorination has additional potential benefits. Fluorine is a hydrogen isostere conferring metabolic stability, H-bond acceptor ability, and altered lipophilicity on pharmaceuticals. 12 Diagnostic applications of fluorinated probes include multimodal 13 and responsive 14 systems. 19 F-MRI is a promising low-background technique, 15 and 18 F is an attractive PET label. 16,17 Fluorinated carbostyrils were incorporated into do3a (1,4,7,10tetraazacyclododecane-1,4,7-triacetate)-based octadentate ligands to enable comparison with previously reported structures. 4,5 The Eu(III), Tb(III), and Gd(III) chelates of the ligands were characterised using 1 H NMR spectroscopy, cyclic voltammetry, and UV-vis absorption and steady-state and time-resolved emission spectroscopies. Our results show fluorination meaningfully impacts the antenna and Ln(III) photophysical properties, and substitution at a remote antenna position could even influence the excited state behaviour of the Ln(III). Fluorinated antennae were synthesised as shown in Scheme 1 and Schemes S1-S6 (ESI †). The procedures were robust, scalable (e.g. 466 mg of CS 6F was obtained in one experiment), and reproducible. Olefins 5 F were prepared from commercially available starting materials as the Z isomers with excellent selectivity due to the steric clash between the ester group and the aromatic ring. 18 The stereochemical assignment was based on the 3 J HF = 33-38 Hz and 3 J HH = 15-16 Hz coupling constants. The key photochemical olefin isomerisationcyclisation was carried out by irradiating a 100 mM solution of 5 in MeOH or EtOH with 254 nm-UV light, giving CS 3F , CS 5F , and CS 6F in good to excellent yield. Regioisomer identities were confirmed by 1D and 2D NMR spectroscopy and single-crystal X-ray crystallography (Fig. S1-S6 and Tables S1-S3, ESI †). The analogous CS 4F could not be accessed via similar routes due to the instability of the intermediates (Schemes S3-S5, ESI †). CS/ CS F was acetylated with Ac 2 O or chloroacetyl chloride to yield reference compounds AcCS/AcCS F , or the reactive antennae 6, respectively. 6 were incorporated into LnL (Ln = Gd, Eu, Tb) using procedures previously developed for similar compounds. Synthetic details, compound characterisations, and the attempted syntheses of CS 4F are given in the ESI. † Analytical data were fully consistent with the assigned structures.
Solution structures of EuL F were studied by paramagnetic 1 H and 19 F NMR spectroscopy. In CD 3 OD at r.t. the 1 H NMR spectra of EuL 3F , EuL 5F , EuL 6F , and EuL H , were similar ( Fig. S7-S10, ESI †). The major isomer had square antiprismatic geometry (4 peaks at 432 ppm). Trace amounts of the twisted square antiprismatic isomer were also present (signals at 12-16 ppm). 19 F NMR spectra supported this interpretation, showing a single peak at À133.8, À118.8, and À134.1 ppm for EuL 3F , EuL 5F , and EuL 6F , respectively (Fig. S11-S13, ESI †). These data are consistent with the ligands imposing similar geometries on the Ln(III) ions in solution in the ground state, and is similar to what has been observed for other do3a-complexes carrying carbostyril antennae. 6 This was expected as fluorine is small, and the fluorination sites are quite distant from the Ln(III).
The photophysical properties of CS and CS F were recorded in acetonitrile due to their low aqueous solubility. The lowestenergy bands in the absorption spectra were assigned to p-p* transitions, and were located at 320-360 nm with l max = 335, 332, and 339 nm for CS 3F , CS 5F , and CS 6F , respectively (Fig. S18-S22, ESI †), non-fluorinated CS had l max = 337 nm. CS, CS 3F , CS 5F , and CS 6F excitation at l max resulted in fluorescence emission maxima at l em = 384, 400, 387, and 382 nm, respectively (Table 1 and Fig. S23-S27, ESI †). CS 3F had the highest fluorescence quantum yield, F L = 56%. Fluorination in the 5position had minimal effect on F L compared to CS (F L = 25 and 27%, respectively), while substitution in the 6-position lowered F L to 10%. CS F fluorescence lifetimes (t fl ) mirrored the observations made for F L (Table 1). CS 3F had the longest t fl (2.84 ns), and CS 6F the shortest, t fl = 0.41 ns. CS and CS 5F had very similar t fl , 1.15 and 1.09 ns, respectively (Table S5 and Fig. S49-S56, ESI †).
Gd(III) excited states are too high to accept energy from the antennae, therefore, GdL are useful for determining the Scheme 1 Preparation of CS F , AcCS, AcCS F , and LnL F .  antenna photophysical properties in LnL without interference from photo-or redox-active Ln(III). Carbostyril excitation in GdL returned antenna fluorescence that was blue-shifted and less intense than that of the corresponding 7-aminocarbostyril ( Fig. S33-S36, ESI †). F L was largest for GdL 3F (13%) and smallest for GdL 6F (5.9%), with F L (GdL 5F ) = 6.1% and F L (GdL H ) = 7.6% in between. Steady state emission spectra were recorded at 77 K to determine the antenna T 1 (Fig. S45-S48, ESI †).
Notably, fluorination in all three investigated positions lowered the antenna T 1 from 22 500 cm À1 in GdL H . GdL 3F had the lowest energy T 1 (22 100 cm À1 ), and GdL 5F had the highest, at only 300 cm À1 higher energy. These are small but impactful differences. The 5 D 4 emitting level of Tb(III) is located at 20 400 cm À1 , and the antenna T 1 must be at least B2000 cm À1 higher energy to avoid thermal back energy transfer (BET). Thus, TbL 3F and possibly even TbL 6F (but likely not TbL 5F ) may be susceptible to BET. Tb(III) complexes that undergo BET are oxygen sensitive, and are useful for O 2 -sensing and cytotoxic singlet oxygen generation. 19,20 T 1 are B5000 cm À1 higher than the emissive 5 D 0 level of Eu(III), which is suitable for Eu(III) sensitization. 21 T 1 in LnL F are closer to the accepting 5 D 2 Eu(III) level (21 500 cm À1 ) than in LnL H , which may result in better energy transfer in the fluorinated complexes. 21,22 Excitation of TbL and EuL at l max yielded green and red Ln(III) luminescence, respectively ( Fig. 2 and Fig. S37-S44, ESI, † Table 2), with residual antenna fluorescence. TbL had slightly lower F L than the analogous GdL likely due to some antenna S 1mediated EnT to Tb(III). 6 EuL had drastically diminished F L , which may be due to a combination of EnT from S 1 , and depopulation of S 1 by PeT. AcCS F oxidation potentials (E ox ) were found by cyclic voltammetry as +1.73, +1.86, and +1.77 V (vs. NHE, for AcCS 3F , AcCS 5F , AcCS 6F , respectively); only 5fluorination made antenna oxidation more difficult than in AcCS (E ox = +1.81 V). PeT was calculated to be slightly less thermodynamically favoured in EuL 5F , and EuL 6F than in EuL H , and more favoured in EuL 3F (DG(PeT) = À1.01, À1.14, À0.98, and À0.97 eV, for EuL H , EuL 3F , EuL 5F , and EuL 6F , respectively (see ESI † for details)). Thus, the effects of fluorination on the antenna S 1 , T 1 and E ox , and in turn on DG(PeT) can be difficult to predict.   The Ln(III) luminescence lifetimes (t H2O ) were measured by timeresolved emission spectroscopy. The decays were monoexponential. t H2O values varied for Ln = Tb but were almost identical for all EuL (B0.61 ms) (Table S4, ESI †). The number of Ln(III)-bound water molecules (q) were q = 1 for EuL. Deviations for TbL from q = 1 could be due to BET, which makes this method inapplicable, 24,25 or the result of the typical error of q AE0.5.
TbL 5F and TbL H had the highest Tb-centred luminescence quantum yields (F Ln = 21.7% and 22.5%, respectively, values identical within experimental error). The low F Ln of TbL 3F is presumably the result of BET. EuL 5F and EuL 6F had F Ln B5%, which is higher than most Eu(III) complexes with similar structures, i.e. uncharged do3a-based emitters with secondary amide-linked carbostyril antenna, including EuL H (F Ln = 4.34%). EuL 3F , however, had low F Ln = 1.09%. Unlike TbL 3F , EuL 3F does not suffer from BET, therefore, an alternative explanation for the poor performance of this emitter was necessary.
F Ln is the product of the intrinsic quantum yield of the Ln(III) (f Ln Ln ) and the Ln(III) sensitisation efficiency (Z sens , eqn (1)), i.e. the efficiency of Ln(III) excited state population. For Eu(III) f Ln Ln can be determined from the corrected emission spectrum. 26 In EuL 5F and EuL 6F Z sens is increased compared to EuL H , presumably due to a combination of the small adjustments in spectral overlap and PeT quenching. EuL 3F had markedly lower Z sens and f Ln Ln than the other EuL ( Table 2). The steady-state and timeresolved EuL 3F emission spectra have different shapes. Eu(III) spectra are sensitive to coordination environment, and these differences indicate the presence of several emissive species. 21 The signal of the slow-decaying component dominating the time-resolved spectrum resembles the EuL 5F /EuL 6F /EuL H spectra. Contribution from the fast-decaying species modifies the steady-state EuL 3F spectrum. If t obs is assumed unchanged, the steady-state spectral shape yields a lower overall f Ln Ln ( Table 2). The spectrum of TbL 3F is similarly time-dependent, but not those of Eu/TbL 5F and Eu/TbL 6F . The reasons for the diminished Z sens of EuL 3F are unclear. PeT is more favoured in EuL 3F than in EuL 5F and EuL 6F , and EuL F have much lower F L than the corresponding GdL F , which is consistent with PeT quenching. The t fl of EuL F and GdL F , however, cannot be compared directly. The biexponential decay of the EuL F antenna fluorescence suggested the presence of additional emitters to those seen in GdL F . Further work is therefore needed to understand the effect of fluorination on EnT and PeT.
In conclusion, monofluorinated 7-aminocarbostyrils, obtained via a photochemical cyclisation, were competent sensitisers of Eu(III) and Tb(III) emission. The position of the fluorine had a dramatic impact on the antenna and Ln(III) photophysical properties, rendering the emission oxygen-sensitive (TbL 3F , TbL 4F ), and increasing (EuL 5F , EuL 6F ), or decreasing F Ln , (TbL 3F , TbL 6F , EuL 3F ) compared to non-fluorinated LnL H . 5-Fluorination improved Eu(III) emission without negatively impacting Tb(III) luminescence. Remote fluorination influenced the excited-state behaviour of LnL 3F . Work towards the 4-fluorinated isomer, and ligands containing other EWGs than fluorine is ongoing. D. K. did all experiments except the crystallographic analysis, which was done by A. O. K. E. B. designed the project, secured funding, and supervised the work. All authors contributed to data analysis and manuscript writing.