A Near-IR Uncaging Strategy Based on Cyanine Photochemistry

Abstract

The development of photocaging groups activated by near-IR light would enable new approaches for basic research and allow for spatial and temporal control of drug delivery. Here we report a near-IR light-initiated uncaging reaction sequence based on readily synthesized C4′-dialkylamine-substituted heptamethine cyanines. Phenol-containing small molecules are uncaged through sequential release of the C4′-amine and intramolecular cyclization. The release sequence is initiated by a previously unexploited photochemical reaction of the cyanine fluorophore scaffold. The uncaging process is compatible with biological milieu and is initiated with low intensity 690 nm light. We show that cell viability can be inhibited through light-dependent release of the estrogen receptor antagonist, 4-hydroxycyclofen. In addition, through uncaging of the same compound, gene expression is controlled with near-IR light in a ligand-dependent CreERT/LoxP-reporter cell line derived from transgenic mice. These studies provide a chemical foundation that we expect will enable specific delivery of small molecules using cytocompatible, tissue penetrant near-IR light.

Role of Fluorophore Charge on the In Vivo Optical Imaging Properties of Near-Infrared Cyanine Dye/Monoclonal Antibody Conjugates

“…This was purified by preparative HPLC ( 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Molar absorption coefficients (ε) and quantum yields (Φ f ) for unconjugated FNIR-774 and FNIR-Z-759 were measured as previously described in 50 mM PBS (pH 7.4). 29 Fluorophore brightness is defined as the product of ε and Φ f . 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin (Life Technologies), in tissue culture flasks, and in a humidified incubator at 37 °C and an atmosphere of 95% ai...…”

A Comprehensive Analysis in Terms of Molecule-Intrinsic Quasi-Atomic Orbitals. IV. Bond Breaking and Bond Forming along the Dissociative Reaction Path of Dioxetane

“…To see whether letting the Op orbitals be active introduces significant changes, the present CAS (8,8) calculations were extended to CASCI (12,10) calculations by adding to the CAS (8,8) The inclusion of the Op orbitals in the active space makes no essential difference for the ground state because the Op orbitals remain doubly occupied also in the CASCI (12,10) calculation. Thus, the CAS (8,8) approach accounts for the same relevant interactions as the CASCI(12,10) approach along the entire reaction paths.…”

Rapid Bioorthogonal Chemistry Turn-on through Enzymatic or Long Wavelength Photocatalytic Activation of Tetrazine Ligation

“…17 While two-photon methods provide high spatial resolution, 18 their very small focal volumes currently limit many practical applications. Recently, near-IR photodecaging strategies have been described based on cyanine 19, BODIPY, 20 and phthalocyanine 21 dyes. 22 A current challenge for red- and near-IR photodecaging strategies lies is the need to improve the kinetics of photorelease.…”