Metal-based Probes Research Articles

Metal complexes in cells: from design of catalytic antioxidants to imaging metal ions and designing metal-based probes in X-ray fluorescence and IR-imaging, a multidisciplinary collaborative journey in bioinorganic chemistry and inorganic chemical biology

Metal complexes in cells: from design of catalytic antioxidants to imaging metal ions and designing metal-based probes in X-ray fluorescence and IR-imaging, a multidisciplinary collaborative journey in bioinorganic chemistry and inorganic chemical biology

A Concerted Enzymatic and Bioorthogonal Approach for Extra- and Intracellular Activation of Environment-Sensitive Ruthenium(II)-Based Imaging Probes and Photosensitizers.

In this article, we report a novel targeting strategy involving the combination of an enzyme-instructed self-assembly (EISA) moiety and a strained cycloalkyne to generate large accumulation of bioorthogonal sites in cancer cells. These bioorthogonal sites can serve as activation triggers in different regions for transition metal-based probes, which are new ruthenium(II) complexes carrying a tetrazine unit for controllable phosphorescence and singlet oxygen generation. Importantly, the environment-sensitive emission of the complexes can be further enhanced in the hydrophobic regions offered by the large supramolecular assemblies, which is highly advantageous to biological imaging. Additionally, the (photo)cytotoxicity of the large supramolecular assemblies containing the complexes was investigated, and the results illustrate that cellular localization (extracellular and intracellular) imposes a profound impact on the efficiencies of photosensitizers.

Advances in assembled micro- and nanoscale mechanical contact probes

The micro- and nanoscale characterization and mapping of surface properties and surface behaviour is critical to both physical and biological science. Mechanical contact probes are a critical tool for investigating surface and interface science, and have seen greater development and a diversification in recent years. In particular, mechanical contact probes that have been fabricated from the bottom-up by the assembly of synthesized nano- or microscale materials can provide enhanced functionality and sensitivity over traditional microcantilevers. This work provides an overview of recent developments in the field of assembled micro- and nanoscale mechanical contact probes, with a specific focus on three probe types: colloidal particle probes with high aspect ratio and a high lateral sensitivity, one-dimensional probes comprising of nanotube and/or nanowire deflection elements, and liquid metal-based probes. For each probe type, the state-of-the-art is reviewed, and their assembly, design, functionality and capabilities are discussed. An outlook on the future direction of probe development and potential applications is also given.

Metal-Based G-Quadruplex Binders for Cancer Theranostics.

The ability of fluorescent small molecules, such as metal complexes, to selectively recognize G-quadruplex (G4) structures has opened a route to develop new probes for the visualization of these DNA structures in cells. The main goal of this review is to update the most recent research efforts towards the development of novel cancer theranostic agents using this type of metal-based probes that specifically recognize G4 structures. This encompassed a comprehensive overview of the most significant progress in the field, namely based on complexes with Cu, Pt, and Ru that are among the most studied metals to obtain this class of molecules. It is also discussed the potential interest of obtaining G4-binders with medical radiometals (e.g., 99mTc, 111In, 64Cu, 195mPt) suitable for diagnostic and/or therapeutic applications within nuclear medicine modalities, in order to enable their theranostic potential.

Metal-Free Organo-Theranostic Nanosystem with High Nitroxide Stability and Loading for Image-Guided Targeted Tumor Therapy.

The desire for all-organic-composed nanoparticles (NPs) of considerable biocompatibility to simultaneously diagnose and treat cancer is undeniably interminable. Heretofore, metal-based agents dominate the landscape of available magnetic resonance imaging (MRI) contrast agents and photothermal therapeutic agents, but with associated metal-specific downsides. Here, an all-organic metal-free nanoprobe, whose appreciable biocompatibility is synergistically contributed by its tetra-organo-components, is developed as a viable alternative to metal-based probes for MRI-guided tumor-targeted photothermal therapy (PTT). This rationally entails a glycol chitosan (GC)-linked polypyrrole (PP) nanoscaffold that provides abundant primary and secondary amino groups for amidation with the carboxyl groups in a nitroxide radical (TEMPO) and folic acid (FA), to obtain GC-PP@TEMPO-FA NPs. Advantageously, the appreciably benign GC-PP@TEMPO-FA features high nitroxide loading (r1 = 1.58 mM-1 s-1) and in vivo nitroxide-reduction resistance, prolonged nitroxide-systemic circulation times, appreciable water dispersibility, potential photodynamic therapeutic and electron paramagnetic resonance imaging capabilities, considerable biocompatibility, and ultimately achieves a 17 h commensurate MRI contrast enhancement. Moreover, its GC component conveys a plethora of PP to tumor sites, where FA-mediated tumor targeting enables substantial NP accumulation with consequential near-complete tumor regression within 16 days in an MRI-guided PTT. The present work therefore promotes the engineering of organic-based metal-free biocompatible NPs in synergism, in furtherance of tumor-targeted image-guided therapy.

From Zn(II) to Cu(II) Detection by MRI Using Metal-Based Probes: Current Progress and Challenges.

Zinc and copper are essential cations involved in numerous biological processes, and variations in their concentrations can cause diseases such as neurodegenerative diseases, diabetes and cancers. Hence, detection and quantification of these cations are of utmost importance for the early diagnosis of disease. Magnetic resonance imaging (MRI) responsive contrast agents (mainly Lanthanide(+III) complexes), relying on a change in the state of the MRI active part upon interaction with the cation of interest, e.g., switch ON/OFF or vice versa, have been successfully utilized to detect Zn2+ and are now being developed to detect Cu2+. These paramagnetic probes mainly exploit the relaxation-based properties (T1-based contrast agents), but also the paramagnetic induced hyperfine shift properties (paraCEST and parashift probes) of the contrast agents. The challenges encountered going from Zn2+ to Cu2+ detection will be stressed and discussed herein, mainly involving the selectivity of the probes for the cation to detect and their responsivity at physiologically relevant concentrations. Depending on the response mechanism, the use of fast-field cycling MRI seems promising to increase the detection field while keeping a good response. In vivo applications of cation responsive MRI probes are only in their infancy and the recent developments will be described, along with the associated quantification problems. In the case of relaxation agents, the presence of another method of local quantification, e.g., synchrotron X-Ray fluorescence, single-photon emission computed tomography (SPECT) or positron emission tomography (PET) techniques, or 19F MRI is required, each of which has its own advantages and disadvantages.

Luminescence approaches for the rapid detection of disease-related receptor proteins using transition metal-based probes.

Protein biomarkers, particularly abnormally expressed receptor proteins, have been proved to be one of the crucial biomarkers for the rapid assessment, diagnosis, prognosis and prediction of specific human diseases. Transition metal based strategies in particular possess delightful strengths in the in-field and real-time visualization of receptor proteins owing to their unique photophysical properties. In this review, we highlight recent advances in the development of detection methods for receptor protein biomarkers using transition metal based approaches, particularly those employing transition metal complexes. We first discuss the strengths and weaknesses of various strategies used for protein biomarker monitoring in live cells. We then describe the principles of the various sensing platforms and their application for receptor protein detection. Finally, we discuss the challenges and future inspirations in this specific field.

BIOBOARD

ASIA – New findings reveal a key cause of failed pregnancies and birth defects. ASIA – Uncontrolled hypertension in rural communities. ASIA – HKBU develops world-first metal-based probes for detection of dopamine receptors, a cancer biomarker. ASIA – Activation switch for cancer metastasis discovered. ASIA – NUS researchers uncover novel pathway in development of acute myeloid leukemia with poor prognosis. ASIA – Southern Campus of Academia Sinica officially breaks ground. ASIA – Singapore team finds new molecule that can grow blood stem cells for transplant. ASIA – Faster genome evolution methods to transform yeast for industrial biotechnology. ASIA – Cometh the cyborg: improved integration of living muscles into robots. ASIA – Pigs that digest their nutrients could reduce pork industry’s carbon footprint.

Mapping neuroreceptors with metal-labeled radiopharmaceuticals.

The growing epidemiological and economic burden of neurological diseases on society is tremendous. A correct and timely diagnosis can help in lowering the burden and improving the life quality of both the diseased person and the caretaker. Imaging of the brain (neuroimaging) using CT, MRI, and nuclear imaging methods can provide anatomical and functional information. Neuroreceptors are central to neurotransmission and neuromodulation in the CNS. In vivo imaging of receptors in the brain provides powerful tools for the functional study of the central nervous system (CNS) in normal or diseased states. Presently, PET imaging using non-metallic radiotracers dominates the imaging of neuroreceptors. Metal-based probes for SPECT and PET can be economical and logistically easier to use without compromising the information. This review focuses on the development of metallic radiotracers for (99mTc) SPECT and (68Ga) PET along with future directions based on the metallic probes developed for other imaging modalities namely MRI.

Achieving Reversible Sensing of Nitroxyl by Tuning the Ligand Environment of Azamacrocyclic Copper(II) Complexes.

To elucidate the factors that impart selectivity for nitroxyl (HNO) over nitric oxide (NO), thiols, and H2S in metal-based fluorescent probes, we investigated five Cu(II)-cyclam (14-N4) derivatives. Upon exposure to NO gas at pH 7, no changes occur in the UV-vis spectra of any of the complexes. Addition of Angeli's salt to generate HNO promotes reduction of Cu(II) only in the case of [Cu(II)(14-N4-Ts)(OTf)2], which has the most positive reduction potential of the series. To gain insight into the observed reactivity, we prepared the Cu(II) complex of the mixed thia/aza 14-N2S2 ligand. [Cu(II)(14-N2S2)(OTf)2] reacts reversibly with HNO at pH 7, although nonselectively over thiols and H2S. The recurrent sensing of HNO uncovered with the study of Cu(II) azamacrocyclic complexes is a remarkable feature that opens the door for the design of a new generation of metal-based probes.

Advances in Metal-Based Probes for MR Molecular Imaging Applications

The role of MRI in the armory of diagnostic modalities for the medicine of the forthcoming years largely depends on how chemistry will provide advanced tools to meet the medical needs. This review aims at outlining the most innovative approaches that have been undertaken in the recent history of MRI contrast agents for tackling the challenges of sensitivity and specificity required by the new generation of contrast agents that should allow the visualization of pathological processes occurring on cellular and molecular scale (the so-called Molecular Imaging). Most of the classes of MRI agents clinically approved or currently under investigation in a preclinical phase exploit peculiar magnetic properties of metals. The conventional agents acting as T(1) or T(2)/T(2)* relaxation enhancers are primarily based on the paramagnetic or the superparamagnetic properties of Gd(III)-, Mn(II)- and iron oxides systems. Recently, there has been a renewed interest towards paramagnetic lanthanide complexes with an anisotropic electronic configuration thanks to their ability to induce strong effect on the resonance frequency of the spins dipolarly coupled with them. Such systems, formerly mainly used as shift reagents, have now attracted much attention in the emerging field of Chemical Exchange Saturation Transfer (CEST) MRI agents.

Synthesis, characterization, DFT studies and DNA binding of mixed platinum (II) complexes containing quinoxaline and 1,2-dithiolate ligands

The complexes Pt(pq)Cl 2 (1) and Pt(pq)(bdt) (2) (where pq = 2-(2′pyridyl)quinoxaline and bdt = benzene-1,2-dithiolate) have been synthesized and fully characterized by UV–visible (UV–Vis), Fourier Transformer Infrared Spectra (FTIR), 1 and 2D NMR and cyclic voltammetry (CV). Interactions of the tested systems (the aforementioned complexes 1 and 2) and the free ligands pq and bdt with double stranded calf thymus DNA (CT-DNA) were studied by UV-spectrophotometric (melting curves) and circular dichroism (CD) measurements. The results suggest that both complexes 1 and 2, are able to form adducts with DNA and to distort the double helix by changing the base stacking. Complex 2 forms stronger adducts to CT-DNA than complex 1 and this is probably due to the substitution of the chlorine atoms of 1 by the 1,2-dithiolate ligand (bdt) in 2. The latter induces an extensive distortion in the planarity of 2 as density functional theory (DFT) calculations reveal. Besides, the light absorbing complex 2 possess intense mixed metal ligand to ligand charge transfer (MM′LLCT) transition in the visible region of the spectrum and could act as photoluminescent metal-based probe for the study of DNA binding. Thus, the photocleavage of DNA by 2 has been studied by UV–Vis and CD spectra and monitored by agarose gel electrophoresis. Under our experimental conditions, it is unclear that complex 2 can photocleave DNA. Furthermore, the ability of 2 to inhibit proliferation of human tumor cell lines was tested and the results indicate some cytoxytic effect on the SF-286 cells.

Cell surface binding of colloidal iron and Limax flavus agglutinin compared by X‐ray microanalysis.

The surface characteristics of tumour cells and T-cell hybridoma variants were examined by quantitative X-ray microanalysis using metal-based probes. Comparisons of populations of cells differing in invasive potential revealed differences in the binding of positive colloidal iron hydroxide, a general probe for anionic sites. Substantial differences between populations were also detected by the binding of Limax flavus agglutinin, which was used in conjunction with fetuin-gold as a specific marker for sialic acid.