Near-Infrared Fluorophores Containing Benzo[c]heterocycle Subunits

Abstract

The syntheses and spectroscopic properties of eight new push-pull type near-infrared fluorophores that contain either isobenzofuran or isothianapthene subunits are presented. The isobenzofuran dyes demonstrate significantly red-shifted absorption from their isothianaphthene counterparts, which is attributed to isobenzofuran's more potent pro-quinoidal character.In vivo near-infrared (NIR) fluorescence imaging is rapidly emerging as a powerful diagnostic method. 1 In the NIR region (650-900nm) biological chromophores exhibit low absorption and autofluorescence 2 thus allowing photons to pass through the tissue and rendering this technique relatively non-invasive. With applications such as vascular mapping of the heart 3 and brain 4 and visualization of various pathologies including tumors 5 , atherosclerosis 6 , and β-amyloid plaques 7 , the demand for new NIR fluorescent contrast agents is ever increasing.Our group resently reported the synthesis and in vivo imaging properties of NIAD-4 (1), NIM-1 (2), and NIM-2 (3), all donor-acceptor type dyes. 7a,8 In the case of 2 and 3, it was found that the incorporation of benzo [c] Isothianapthene has a relatively long history as a component in functional materials, with examples in fluorophores, 9 OLEDs, 10 photovoltaics, 11 and low band-gap polmyers, of which polyisothianaphthene (PITN) 12 is the progenitor. The smaller band-gap of these ITN containing materials over similar thiophene containing materials is a result of the increased contribution of the quinoid resonance structure (Figure 2) due to the stabilization achieved by aromatization of the benzene ring. 13 In contrast, only a few examples 14 of functional materials containing isobenzofuran are reported in the literature, presumably due its reduced stability. 15 For this reason, we predicted that IBF would prove even more pro-quinoidal and that its incorporation into donor-acceptor dyes would further reduce the band-gap of these materials.In order to test this principal, we synthesized a series of IBF and ITN dyes similar to NIAD-4 (Scheme 1). Four different electron donating (R) groups, H-, MeO-, HO-, and Me 2 N-, were incorporated in order to span a range of wavelengths. Appropriately substituted aryl-lactones 5a-d were either purchased or synthesized via acid mediated condensation 16 of 2-carboxybenzaldehyde and substituted benzenes. In the case of the phenol group (R = OH), TiPS protection was employed. Initially, the IBF framework was constructed with a free 5 position on the thiophene, which was subsequently lithiated and the formylated with DMF. However, these unsubstituted intermediate compounds proved relatively difficult to isolate and purify, resulting in poor yields for the formylation.Exploiting the acetal protected aldehydes allowed us to bypass these troublesome intermediates. Protected aldehydes 7a-d were produced in one step by reaction of the lactones with the lithio-derivative of 6 17 followed by dehydration with acetic anhydride and deprotection with aqueous acetic acid. Knoevenega...

Functional Oligothiophenes: Molecular Design for Multidimensional Nanoarchitectures and Their Applications

“…813 Push-pull-type fluorophores comprising MeO-, HO-, and Me 2 N-groups as donor and dicyanovinylene as acceptor were synthesized as NIR contrast agents for biomedical applications. 814 Hong et al synthesized two air-stable p-type organic semiconductors, which have a symmetrically substituted 2,7-divinylbenzothieno[3,2-b]benzothiophene backbone. They showed good electrical performances on a SiO 2 /Si substrate and high field-effect mobilities up to 0.4 cm 2 V -1 s -1 .…”

Synthesis, structure, and electronic study of some group VII furoyl substituted complexes

“…In other cases, the incorporation of furans led to materials with properties superior to those containing thiophenes. Meek and coworkers found that the use of IBFs over isothianapthenes (ITNs) led to improved dyes for near-infrared (NIR) fluorescence imaging [15]. Likewise, recent studies on oligofurans show better solid state and optical properties as compared to oligothiophenes [16].…”

Synthesis and characterization of naphth-annelated thiophene analogs

“…Emission values of the naphtho[c]thiophenes clearly indicated that they can be explored Far-IR fluorophore applications. 16 Research is in progress to synthesize push-pull systems involving naphtho[c]thiophene unit.…”

“…15 Recently, Swager and co-workers reported the synthesis of push-pull-type near-IR fluorophores containing isobenzofuran and isothianaphthene subunits. 16 Cava and co-workers reported the synthesis and electropolymerization of 1,3-dithienylnaphtho[c]thiophene 3. 17 Even after fifteen years of this first report, with the exception of parent naphtho[c]thiophene 18 till date any further derivative of isothiaanthracene (ITA) is yet to be explored.…”