NIR‐Emissive Alkynylplatinum(II) Terpyridyl Complex as a Turn‐On Selective Probe for Heparin Quantification by Induced Helical Self‐Assembly Behaviour

Abstract

Platinum(II) polypyridyl complexes, adopting squareplanar geometry, have exhibited interesting spectroscopic and luminescence properties, dependent on the extent of d 8 -d 8 metal-metal interaction and p-p stacking of the polypyridyl ligand. [1, 2] With the utilisation of the self-assembly and disassembly processes through such Pt···Pt and p-p interactions of the alkynylplatinum(II) terpyridyl complexes, induced by the multiple negatively charged synthetic polyelectrolytes or biopolymers, recent work by our group has demonstrated the differentiation of various single-stranded nucleic acids, [2b] detection of the conformational changes in G-quadruplexes, [2e, f] probing of enzymatic activities, [2e, g] and the quantification of important proteins and sugars [2f, g] in aqueous media by monitoring the UV/Vis absorption, nearinfrared (NIR) emission and circular dichroism (CD) spectral changes. Such NIR emission and large Stokes shift would make this label-free sensing protocol desirable as the problems of autofluorescence and light scattering arising from the biological environment could be effectively avoided. [3] Heparin, a linear unbranched polydispersed polysaccharide consisting of repeating disaccharide units of iduronic acid and glucosamine (Scheme 1), is prevalent and possesses one of the highest negative charge densities amongst the biological macromolecules due to the presence of numerous sulfate and carboxylate groups.[4] Most importantly, heparin is pharmacologically functional as an anticoagulant because of its capability to accelerate the antithrombin III (ATIII)-mediated inactivation of serine proteases in the coagulation cascade upon its electrostatic interaction with ATIII through a specific pentasaccharide sequence.[4-6] Unfractionated heparin (UFH) and the chemically or enzymatically fractionated low-molecular-weight heparin (LMWH) are the two forms of heparin in clinical use. In order to prevent the catastrophic hemorrhagic complications and heparin-induced thrombocytopenia (HIT) arising from over usage, [5,7] the control of heparin dosage levels in surgery and postoperative treatment is of pivotal importance. Therefore, various traditional clinical heparin administration assays, such as activated partial thromboplastin time (aPTT), have been established, yet these indirect methods are not accurate and suffer from potential interference from other factors.[8] Recently, a list of fluorescent, colorimetric and electrochemical methods [9] have been designed for the quantification of heparin, of which only few can measure both UFH and LMWH within the clinical range and effectively differentiate heparin from structurally similar analogues as well.[9e] Moreover, striking clinical evidence has revealed the prominent inhibiting effect of heparin treatment on tumour metastasis, [4,10] and thus there is a strong demand for the design of selective and practical detection techniques.With the utilisation of such high anionic charge density, we herein demonstrate the heparin-induced self-assembly of an N...

Conjugated Polyelectrolyte‐Induced Self‐Assembly of Alkynylplatinum(II) 2,6‐Bis(benzimidazol‐2′‐yl)pyridine Complexes

“…6e, 7, 8d Extension of the work to the design of systems which self‐assemble into supramolecular architectures, for example metallogels,4b,c, 6b, g and molecular architectures like nanostructures,6d–f, 7b hairpin structures,6a,b helices,3 and molecular tweezers,8 has also been made. Recently, our group has demonstrated the self‐assembly of cationic alkynylplatinum(II) terpyridine complexes induced by the electrostatic interactions with polyanionic synthetic polyelectrolytes9a–d, 10 and biopolymers such as single‐stranded nucleic acids, aptamers, heparin and carboxylic curdlan,9e–g,k which shows remarkable UV/Vis absorption and near‐infrared (NIR) emission spectral changes. Label‐free detection and quantification of various biologically important macromolecules, including their conformational changes and enzymatic activities, can be achieved through the exploitation of such significant spectral changes arising from the assembly‐disassembly behavior of the platinum(II) complexes 9d–j.…”

Supramolecular Assembly of Metal‐Ligand Chromophores for Sensing and Phosphorescent OLED Applications

“…In light of the fact that linear, unbranched polydispersed polysaccharides possess the highest negative charge densities amongst the biological macromolecules, heparin has been employed in the self‐assembly of supramolecular nanostructures based on a water‐soluble alkynylplatinum(II) terpyridine complex, [Pt(terpy){C≡C‐C 6 H 4 ‐CH 2 O‐C 6 H 3 ‐(CH 2 OH) 2 ‐3,5}]OTf, which can be extended for use as a luminescence probe for the development of a convenient sensing protocol for the quantification of unfractionated heparin (UFH) and the chemically or enzymatically fractionated low‐molecular‐weight heparin (LMWH) in buffer and biological medium ( Figure a) . On the basis of the luminescence spectral changes in the NIR region arising from the induced self‐assembly of the platinum(II) complexes, the extent of this self‐assembly in the presence of heparin with such high anionic charge density has been employed for the sensing of the heparin macromolecule in high sensitivity and versatility.…”

“…Schematic cartoon showing the aggregation of platinum(II) complex molecules onto (a) heparin, (b) PAAPBA formed upon glucose binding, (c) G‐quadruplex formed upon K + ion binding, and (d) schematic cartoon showing the disassembly of platinum(II) complex molecules from LA upon lysozyme binding or from TBA‐hemin upon thrombin binding. Reproduced with permission . Copyright 2009, 2010 and 2011, The Royal Society of Chemistry; Copyright 2011, Wiley‐VCH.…”

Effect of buffer on heparin binding and sensing in competitive aqueous media

“…This sensor relies on well-organised electrostatic interactions between its cationic groups and the anionic sites on the heparin, and can operate at clinically relevant concentrations in highly competitive conditions, such as the presence of 150 mM NaCl and/or human serum. In this field of research, there has been considerable focus on developing systems which operate effectively in competitive media (33)(34)(35)(36)(37)(38)(39) Given the fact that different aqueous solutions can be very different, and buffer may have significant impacts on binding, we therefore wanted to explore the impact of buffer on MalB. In particular we wished to compare the binding and sensing in different buffers.…”