Recent advances in Gd-chelate based bimodal optical/MRI contrast agents

Verwilst, Peter,Park, Soyeon,Yoon, Byungkwon,Kim, Jong Seung The Royal Society of Chemistry 2015 Chemical Society reviews Vol.44 No.7

<P>Research on bimodal contrast agents in general and optical/MRI contrast agents in particular has attracted increased attention from the scientific community in recent years. Whereas optical contrast agents reveal pathologies at the cellular or sub-cellular level, MRI contrast agents generally report physiological differences at the level of tissues and organs. The complementary information obtained from these two techniques allows for a more precise diagnosis. Furthermore the emergence of near-infrared luminophores accommodates the simultaneous detection of optical and MRI signals. The current multitude and diversity in molecular architectures mirrors the ever increasing interest in the field. In this review the developments between 2010 and mid-2014 are highlighted.</P> <P>Graphic Abstract</P><P>Recent developments in the field of bimodal MRI/optical contrast agents, based on Gd<SUP>3+</SUP>-chelates are presented. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cs00336e'> </P>

The role of copper ions in pathophysiology and fluorescent sensors for the detection thereof

Verwilst, Peter,Sunwoo, Kyoung,Kim, Jong Seung The Royal Society of Chemistry 2015 Chemical communications Vol.51 No.26

<P>Copper ions are indispensible to life and maintaining tight control over the homeostasis of copper ions in the body is a prerequisite to sustaining health. Aberrations in normal copper levels, both systemic as well as on a tissue or cellular scale, are implicated in a wide range of diseases, such as Menkes disease, Wilson's disease, Alzheimer's disease, Parkinson's disease and transmissible spongiform encephalopathy (prion diseases). The current understanding of how copper influences these diseases is described. The field of fluorescent copper sensors both functioning <I>via</I> a reaction based mechanism as well as by directly binding copper ions has known an inflation in recent years, and the importance of this field to elucidating the role of copper in cell biology is pointed out. Progress in these tightly interwoven fields has resulted in a better understanding of a number of diseases related to copper imbalances and current developments might open the path for novel and innovating therapies to address these diseases.</P> <P>Graphic Abstract</P><P>Copper ions are crucial to life, and some fundamental roles of copper in pathophysiology have been elucidated using fluorescent sensors. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cc10366a'> </P>

Shedding light on tau protein aggregation: the progress in developing highly selective fluorophores

Verwilst, Peter,Kim, Hyeong Seok,Kim, Soobin,Kang, Chulhun,Kim, Jong Seung The Royal Society of Chemistry 2018 Chemical Society reviews Vol.47 No.7

<P>Historically, in Alzheimer's disease research, a lot of attention has been paid to the development of highly selective fluorophores for beta amyloid plaques. With a shift in the understanding of the disease and the importance of a network of cross-talk interactions, the development of small-molecule fluorescent dyes with high selectivity for (hyperphosphorylated) tau protein aggregates in neurofibrillary tangles has been gaining increasing attention. Fluorescent dyes for the selective labelling of tau aggregates in histological AD brain sections have been described, spanning the entire visible range of the electromagnetic spectrum. Despite the relatively early stages of the development of the field, a large diversity in probe architectures has been reported. Importantly, a handful of near-infrared-emissive dyes have been described as well, and some of these have exhibited good pharmacological profiles, with a significant blood-brain-barrier permeability, and a demonstrated ability to label tau tangles<I>in vivo</I>in small-animal models of Alzheimer's disease and other tauopathies. The developments summarized in the current work are expected to aid the unravelling of the diverse set of players in the etiology of Alzheimer's disease. In this tutorial review, we seek to provide the reader with an overview of the most important recent developments and hope to provide some guidelines for the design of future probes.</P>

Rational Design of <i>in Vivo</i> Tau Tangle-Selective Near-Infrared Fluorophores: Expanding the BODIPY Universe

Verwilst, Peter,Kim, Hye-Ri,Seo, Jinho,Sohn, Nak-Won,Cha, Seung-Yun,Kim, Yeongmin,Maeng, Sungho,Shin, Jung-Won,Kwak, Jong Hwan,Kang, Chulhun,Kim, Jong Seung American Chemical Society 2017 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.139 No.38

<P>The elucidation of the cause of Alzheimer's disease remains one of the greatest questions in neurodegenerative research. The lack of highly reliable low-cost sensors to study the structural changes in key proteins during the progression of the disease is a contributing factor to this lack of insight. In the current work, we describe the rational design and synthesis of two fluorescent BODIPY-based probes, named Tau 1 and Tau 2. The probes were evaluated on the molecular surface formed by a fibril of the PHF6 ((306)-vulyio(311)) tau fragment using molecular docking studies to provide a potential molecular model to rationalize the selectivity of the new probes as compared to a homologous A beta-selective probe. The probes were synthesized in a few steps from commercially available starting products and could thus prove to be highly cost-effective. We demonstrated the excellent photophysical properties of the dyes, such as a large Stokes shift and emission in the near-infrared window of the electromagnetic spectrum. The probes demonstrated a high selectivity for self-assembled microtubule-associated protein tau (Tau protein), in both solution and cell-based experiments. Moreover, the administration to an acute murine model of tauopathy clearly revealed the staining of self-assembled hyperphosphorylated tau protein in pathologically relevant hippocampal brain regions. Tau 1 demonstrated efficient blood brain barrier penetrability and demonstrated a clear selectivity for tau tangles over A beta plaques, as well as the capacity for in vivo imaging in a transgenic mouse model. The current work could open up avenues for the cost-effective monitoring of the tau protein aggregation state in animal models as well as tissue staining. Furthermore, these fluorophores could serve as the basis for the development of clinically relevant sensors, for example based on PET imaging.</P>

In Vivo Imaging of Endogenously Produced HClO in Zebrafish and Mice Using a Bright, Photostable Ratiometric Fluorescent Probe

Duan, Chong,Won, Miae,Verwilst, Peter,Xu, Junchao,Kim, Hyeong Seok,Zeng, Lintao,Kim, Jong Seung American Chemical Society 2019 ANALYTICAL CHEMISTRY - Vol.91 No.6

<P>A high brightness red fluorescent probe (<B>S-BODIPY</B>) has been developed for the sensitive and specific imaging of HClO/ClO<SUP>-</SUP> in vitro and in vivo. This probe exhibits some distinctive features such as excellent resistance to photobleaching, a high fluorescence brightness, high selectivity, as well as a good biocompatibility. Upon oxidation of the thio-ether group into sulfoxide, the probe showed a noticeable ratiometric fluorescence response toward ClO<SUP>-</SUP> with fast response (within 30 s) and a low detection limit (59 nM). The probe demonstrated the successful imaging of exogenous and endogenous HClO/ClO<SUP>-</SUP> in living HeLa cells, zebrafish, and mice with high signal-to-noise ratios. <B>S-BODIPY</B> allows for the real-time monitoring the level of ClO<SUP>-</SUP> in living cells by ratiometric fluorescence imaging, opening up exciting prospects to develop red and even near-infrared BODIPYs with high brightness and good photostability for in vivo imaging.</P> [FIG OMISSION]</BR>

Organelle-selective di-(2-picolyl)amine-appended water-soluble fluorescent sensors for Cu(II): synthesis, photophysical and in vitro studies

Lee, Yun Hak,Verwilst, Peter,Park, Nayoung,Lee, Joung Hae,Kim, Jong Seung Springer-Verlag 2015 JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHE Vol.82 No.1

Fluorescent and colorimetric sensors for the detection of humidity or water content

Jung, Hyo Sung,Verwilst, Peter,Kim, Won Young,Kim, Jong Seung The Royal Society of Chemistry 2016 Chemical Society reviews Vol.45 No.5

<P>In this tutorial review, we describe the current state of the art in water sensors and provide an overview of the major advances made in this field post 2000. The field is currently still in its early development stages and subject to continuous improvements, and the current work provides a structured approach describing different sensing mechanisms and potential future applications associated with each of these. With these developments and their potential implications for the diverse scientific fields requiring tight control over the water content, we strongly believe the discipline is potentially at the threshold of translation into more widespread application and we hope the current review might allow for an expedited process thereof.</P>

Coumarin-Based Small-Molecule Fluorescent Chemosensors

Cao, Duxia,Liu, Zhiqiang,Verwilst, Peter,Koo, Seyoung,Jangjili, Paramesh,Kim, Jong Seung,Lin, Weiying American Chemical Society 2019 Chemical reviews Vol.119 No.18

<P>Coumarins are a very large family of compounds containing the unique 2<I>H</I>-chromen-2-one motif, as it is known according to IUPAC nomenclature. Coumarin derivatives are widely found in nature, especially in plants and are constituents of several essential oils. Up to now, thousands of coumarin derivatives have been isolated from nature or produced by chemists. More recently, the coumarin platform has been widely adopted in the design of small-molecule fluorescent chemosensors because of its excellent biocompatibility, strong and stable fluorescence emission, and good structural flexibility. This scaffold has found wide applications in the development of fluorescent chemosensors in the fields of molecular recognition, molecular imaging, bioorganic chemistry, analytical chemistry, materials chemistry, as well as in the biology and medical science communities. This review focuses on the important progress of coumarin-based small-molecule fluorescent chemosensors during the period of 2012-2018. This comprehensive and critical review may facilitate the development of more powerful fluorescent chemosensors for broad and exciting applications in the future.</P> [FIG OMISSION]</BR>

Organic molecule-based photothermal agents: an expanding photothermal therapy universe

Jung, Hyo Sung,Verwilst, Peter,Sharma, Amit,Shin, Jinwoo,Sessler, Jonathan L.,Kim, Jong Seung The Royal Society of Chemistry 2018 Chemical Society reviews Vol.47 No.7

<P>Over the last decade, organic photothermal therapy (PTT) agents have attracted increasing attention as a potential complement for, or alternative to, classical drugs and sensitizers involving inorganic nanomaterials. In this tutorial review, we provide a structured description of the main classes of organic photothermal agents and their characteristics. Representative agents that have been studied in the context of photothermal therapy since 2000 are summarized and recent advances in using PTT agents to address various cancers indications are highlighted.</P>

Targeted combinational therapy inducing mitochondrial dysfunction

Shin, W.,Park, S.,Verwilst, P.,Koo, S.,Lee, J.,Chi, S. G.,Kim, J. Royal Society of Chemistry 2017 Chemical communications Vol.53 No.7

<P>We report on a mitochondria-specific combinational theranostic agent, 1. This system contains a chlorambucil prodrug and an aggregation induced emission dye. In addition, compound 1 bears both an intracellular thiol-triggered moiety and a mitochondria targeting unit (triphenylphosphonium). Glutathione (GSH) is the most abundant thiol and its concentrations are significantly higher in a great number of cancer cell lines, compared to normal cells. The GSH-induced prodrug 1 upon activation releases chlorambucil and exhibits mitochondria targeted aggregation induced emission (AIE) fluorescence, resulting in cell apoptosis via the caspase pathway due to mitochondrial dysfunction.</P>