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Viscosity and temperature variations in the microscopic world are of paramount importance for diffusion and reactions. Consequently, a plethora of fluorescent probes have evolved over the years to enable fluorescent imaging of both parameters in biological cells. However, the simultaneous effect of both temperature and viscosity on the photophysical behavior of fluorophores is rarely considered, yet unavoidable variations in temperature can lead to significant errors in the readout of viscosity and vice versa. Here we examine the effect of temperature on the photophysical behavior of three classes of viscosity-sensitive fluorophores termed ‘molecular rotors’. For each of the fluorophores we decouple the effect of temperature from the effect of viscosity. In the case of the conjugated porphyrin dimer, we demonstrate that, uniquely, simultaneous dual-mode lifetime and intensity measurements of this fluorophore can be used for measuring both viscosity and temperature concurrently.

We report the synthesis of a series of hydrophilic butadiyne-linked conjugated zinc porphyrin dimers (1–7), designed as photodynamic therapy (PDT) agents. These porphyrin dimers exhibit exceptionally high two-photon absorption cross sections (δ_max≈ 8,000–17,000 GM) and red-shifted linear absorption spectra (λ_max≈ 700–800 nm) making them ideal candidates for one-photon and two-photon excited photodynamic therapy. Four polar triethyleneglycol substituents are positioned along the sides of each dimer, but, on their own, these TEG chains do not confer sufficient solubility in aqueous physiological media for reproducible delivery into live cells. Charged cationic (methylpyridinium and trimethylammonium) and anionic (sulfonate and carboxylate) substituents have been appended to the meso-positions of porphyrin dimers using three synthetic strategies: 1) Suzuki coupling, 2) Sonogashira coupling, and 3) nucleophilic Senge arylation. Approaches 1 and 3 both allow attachment of aromatic substituents directly to the meso-positions of porphyrins. Approach 2 provides a route to hydrophilic porphyrin dimers with an ethyne link between the porphyrin and the polar aromatic substituent. The palladium-catalysed approaches 1 and 2 allow the synthesis of a broader range of meso-capped porphyrins, as many aryl halides are available. However the synthesis of the intermediate required for these routes necessitates a statistical reaction step, which decreases the overall yield. On the other hand, Senge-arylation provides highly regioselective nucleophilic aromatic substitution, and offers higher overall yield than the other routes. All these charged dimers exhibit good solubility in polar solvents (e.g. methanol) and aqueous solvent mixtures (aqueous DMSO or DMF).