Polydiacetylene-based ultrastrong bioorthogonal Raman probes for targeted live-cell Raman imaging

Sidan Tian,Shun Wang,Yage Chen,Liang Luo,Fanling Meng,Xiangliang Yang,Huajun Tang,Mingming Yin,Zhong Li,Yuting Gao,Haozheng Li,Ping Wang,Joseph W Lauher

doi:10.1038/s41467-019-13784-0

Abstract

Live-cell Raman imaging based on bioorthogonal Raman probes with distinct signals in the cellular Raman-silent region (1800–2800 cm−1) has attracted great interest in recent years. We report here a class of water-soluble and biocompatible polydiacetylenes with intrinsic ultrastrong alkyne Raman signals that locate in this region for organelle-targeting live-cell Raman imaging. Using a host-guest topochemical polymerization strategy, we have synthesized a water-soluble and functionalizable master polydiacetylene, namely poly(deca-4,6-diynedioic acid) (PDDA), which possesses significantly enhanced (up to ~104 fold) alkyne vibration compared to conventional alkyne Raman probes. In addition, PDDA can be used as a general platform for multi-functional ultrastrong Raman probes. We achieve high quality live-cell stimulated Raman scattering imaging on the basis of modified PDDA. The polydiacetylene-based Raman probes represent ultrastrong intrinsic Raman imaging agents in the Raman-silent region (without any Raman enhancer), and the flexible functionalization of this material holds great promise for its potential diverse applications.

Highlights

Live-cell Raman imaging based on bioorthogonal Raman probes with distinct signals in the cellular Raman-silent region (1800–2800 cm−1) has attracted great interest in recent years
Our approach to the preparation of diynedioic acid (DDA) co-crystals uses bis(pyridyl)oxalamide host 1, which is composed of terminal Lewis basic pyridyl groups and a central oxalamide group that forms a self-complementary hydrogen bonding framework with the required spacing
The complete polymerization of DDA and generation of PDDA within the host–guest co-crystals were characterized by a single crystal X-ray diffraction experiment, as exhibited in Fig. 2b and Fig. 2c

Summary

Introduction

Live-cell Raman imaging based on bioorthogonal Raman probes with distinct signals in the cellular Raman-silent region (1800–2800 cm−1) has attracted great interest in recent years. The C≡C bond Raman peak of the PDDA solution does not change upon irradiation under excitation with different wavelengths (785, 532, and 488 nm, Supplementary Fig. 3).

Results

Conclusion