Cyanine dye labelling reagents with meso-substitution

摘要

Disclosed are cyanine dyes having meso-substituents in the polymethine chain linking the heterocyclic ring systems. The dyes are of formula (1): in which groups R³ and R⁴ are attached to the Z¹ ring structure and groups R⁵ and R⁶ are attached to the Z² ring structure, and n=1, 2 or 3; Z¹ and Z² independently represent the atoms necessary to complete one ring, or two fused ring aromatic or heteroaromatic systems, each ring having five or six atoms selected from carbon atoms and optionally no more than two atoms selected from oxygen, nitrogen and sulphur; X and Y are the same or different and are selected from oxygen, sulphur, -CH-CH- and the group: at least one of groups R¹, R², R³, R⁴, R⁵, R⁶ (and R⁸ and R⁹ if present) is the group -E-F where E is a spacer group and F is a target bonding group; one of groups R⁷ is selected from -CN, -Cl, -F, -CF₃ and -C(O)R¹⁰ wherein R¹⁰ is selected from H, C₁-C₆ alkyl and aryl. Preferred group R⁷ is meso-substituted -CN, which confers an unexpected hypsochromic shift of approximately 40 nm in the emission spectrum, when compared with the corresponding unsubstituted analogue. The dyes are useful for labelling and detecting a variety of target molecules.