A Facile and Reproducible Synthesis of Near-Infrared Fluorescent Conjugates with Small Targeting Molecules for Microbial Infection Imaging

Friederike Reeßing; Mafalda Bispo; Marina López-Álvarez; Marleen van Oosten; Ben L Feringa; Jan Maarten van Dijl; Wiktor Szymański

doi:10.1021/acsomega.0c02094

A Facile and Reproducible Synthesis of Near-Infrared Fluorescent Conjugates with Small Targeting Molecules for Microbial Infection Imaging

ACS Omega. 2020 Aug 26;5(35):22071-22080. doi: 10.1021/acsomega.0c02094. eCollection 2020 Sep 8.

Authors

Friederike Reeßing^{1

2}, Mafalda Bispo³, Marina López-Álvarez³, Marleen van Oosten³, Ben L Feringa^{1

2}, Jan Maarten van Dijl³, Wiktor Szymański^{1

2}

Affiliations

¹ Department of Radiology, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen 9713GZ, The Netherlands.
² Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, Groningen 9747 AG, The Netherlands.
³ Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen 9713GZ, The Netherlands.

Abstract

Optical imaging of microbial infections, based on the detection of targeted fluorescent probes, offers high sensitivity and resolution with a relatively simple and portable setup. As the absorbance of near-infrared (NIR) light by human tissues is minimal, using respective tracers, such as IRdye800CW, enables imaging deeper target sites in the body. Herein, we present a general strategy for the conjugation of IRdye800CW and IRdye700DX to small molecules (vancomycin and amphotericin B) to provide conjugates targeted toward bacterial and fungal infections for optical imaging and photodynamic therapy. In particular, we present how the use of coupling agents (such as HBTU or HATU) leads to high yields (over 50%) in the reactions of amines and IRDye-NHS esters and how precipitation can be used as a convenient purification strategy to remove excess of the targeting molecule after the reaction. The high selectivity of the synthesized model compound Vanco-800CW has been proven in vitro, and the development of analogous agents opens up new possibilities for diagnostic and theranostic purposes. In times of increasing microbial resistance, this research gives us access to a platform of new fluorescent tracers for the imaging of infections, enabling early diagnosis and respective treatment.