Synthesis of a multichromophoric array by sequential CuAAC reactions

Highlights

• A multichromophore triad was synthesized by sequential CuAAC reactions.

• The triad showed FRET behaviour, with high energy transfer efficiencies.

• Computational modelling showed the three chromophores in close proximity.

Abstract

An easily synthesized α-hydroxy-β-azidotetrazole scaffold was used to build a three dimensional polychromic system. Different chromophores (coumarin, BODIPY and distyryl BODIPY) were incorporated into the structure by using sequential CuAAC reactions to form a series of dyads and a triad. A computational study of the resulting arrays showed that the predominant conformations brought the substituents into close spatial proximity. The triad exhibited FRET behaviour with notably efficient energy transfer values.

Introduction

Multifunctional chemical scaffolds which can be orthogonally substituted with varied chemical groups represent important tools in the fields of chemistry and biology[1,2]. From a relatively simple basic structure, complex chemical architectures can be created from such scaffolds in only a few steps, by using successive coupling reactions to associate diverse molecules, such as peptides, nucleotides, carbohydrates or fluorophores. “Click” reactions, which should be high-yielding and regiospecific, are ideal for use in this context[[3], [4], [5], [6], [7]]. The copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction has become the most popular of these reactions, as it is compatible with varied functional groups and requires only mild reaction conditions[[8], [9], [10]].

We recently reported the use of α-hydroxy-β-azidotetrazoles (AHBATs) as substrates for orthogonal CuAAC reactions[11]. These compounds are easily prepared from α,β-epoxynitriles by tin-catalyzed cycloaddition and ring opening with TMSN₃[12]. The azide moiety of these molecules may undergo a first CuAAC reaction with an alkyne, and the α-hydroxytetrazole part subsequently converted to an alkyne by treatment with a dehydrating agent (Scheme 1)[12,13]. This alkyne can then react with an azide in a second CuAAC reaction, leading to unsymmetrical bis-triazoles. This synthetic strategy was found to be compatible with a range of functional groups, and could be used to create structural diversity around the central carbon atom.

The previously described AHBATs constitute a bifunctional scaffold, but we reasoned that additional orthogonal attachment points could be created by introducing suitable reactive moieties at the central carbon atom (groups R¹/R² in Scheme 1) leading to a multifunctional platform, with the substituents placed in a three dimensional arrangement. We considered the use of a piperidine moiety in the AHBAT scaffold, giving an additional orthogonal attachment point, leading to a platform which could bear three different functional groups (Fig. 1). To demonstrate the possibilities of such a scaffold, we decided to functionalize this platform with three different chromophores, giving rise to a multichromophoric array.

Multichromophoric species have been extensively investigated in the last decade[[14], [15], [16]]. These assemblies, where chromophores are associated in covalently linked architectures, are able to harvest sunlight over a broad range of wavelengths, and subsequently concentrate photons at a preferred site by multiple electronic (or excitation) energy transfer (EET) processes. These properties are exploited for energy conversion in artificial photosynthesis and in solar cells[15,[17], [18], [19], [20], [21], [22]]. Moreover, multichromophoric species featuring EET properties are also sought for biomedical applications[23,24]. In addition, assemblies based on host-guest strategies have also led to efficient light harvesting materials[[25], [26], [27], [28]].

Numerous multichromophoric organic architectures with different combinations of chromophores have been described. Among the different chromophores, BODIPY dyes and their derivatives are of particular interest since they display high absorption coefficients, high fluorescent quantum yields and good photostability[[29], [30], [31], [32], [33]]. More importantly, the BODIPY core is easily functionalized, allowing tuning of absorption and emission properties, from the visible to the near infra-red region. Multi-BODIPY systems have been described using various pre-organized platforms [19,20], and the geometry of these scaffolds used to associate the chromophores has a direct influence on the outcome of EET processes. At the most simple level, BODIPY dyes can be directly linked together, or connected through the use of a saturated or unsaturated spacer, leading to basically linear systems[27,[34], [35], [36], [37], [38], [39]]. Two-dimensional systems, where the chromophores are arranged in a plane, can be formed from truxene scaffolds or by using a flat scaffold (including BODIPY) as a central core connecting to several others[[40], [41], [42], [43]]. Three-dimensional systems are more scarce, a few examples have been described using supports such as polymers, [44,45] carbohydrates[46], dendrimers[47,48], fullerene[49], rotaxane [50] and triptycene derivatives[[51], [52], [53]]. In this latter approach, the non-planar spatial arrangement of the multichromophoric arrays may prevent aggregation of the chromophores. However, as the complexity of these scaffolds increases, the need for lengthy synthetic pathways or the limited possibilities to combine different chromophores may become drawbacks.

In this work, we propose to use our AHBAT modified platform with its tetrahedral architecture for the construction of multichromophoric systems. This platform, featuring three different functional groups (piperidine, azide and masked alkyne) with their distinct chemical reactivities, permits the grafting of individual chromophores in an efficient manner. We chose to use as fluorophores 7-diethylaminocoumarin, BODIPY and distyrylBODIPY for their complementary absorptions, that cover the entire visible spectral range. Adequate spectral overlap between the fluorescence donor emission and the acceptor absorption of each pair of chromophores was also considered in this study. The coumarin derivative (Coum) was selected as the short-wavelength donor due to its strong absorption and intense fluorescence in the blue spectral region[54]. The BODIPY dye, (BDP), chosen on the basis of its strong absorption and emission in the green region[55], behaves both as donor and acceptor. Finally, the distyrylBODIPY (DSBDP, acceptor moiety) was selected due to its strong and highly efficient emission in the red/NIR spectral region[56]. The association of a coumarin donor with a BODIPY acceptor within an array has previously been investigated, notably for applications as laser dyes[57], as artificial photosynthetic systems[58], and for analyte detection in living cells[[59], [60], [61]]. Here we describe the synthesis and characterization of three dyads and a triad containing these three chromophores on the same platform. Absorption spectra and photophysical experiments were first conducted on the three dyads to characterise the energy transfer between each pair of chromophores. Finally, the same set of experiments was carried out on the Coum-BDP-DSBDP triad to elucidate the overall EET process in this multichromophoric system.