Tetra-phosphonate Calix[4]pyrrole Cavitands as Multitopic Receptors for the Recognition of Ion Pairs

Ciardi, Moira; Galán, Albano; Ballester, Pablo

doi:10.1021/ja512590j

Cited by 60 publications

(34 citation statements)

References 31 publications

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“…Development of this field is driven by promising applications 23 of these systems in supramolecular catalysis 24 – 29 , protein binding 3 , 30 , cellar imaging 31 , and bio-process monitoring 32 . Although strong binding of choline by artificial receptors has been widely reported 33 – 35 , good selectivity for choline has not yet been achieved 36 – 38 . In nature, the ChoX protein is a specific high-affinity choline transporter and various choline derivatives present no or much weaker binding affinity.…”

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confidence: 99%

Selective binding of choline by a phosphate-coordination-based triple helicate featuring an aromatic box

et al. 2017

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In nature, proteins have evolved sophisticated cavities tailored for capturing target guests selectively among competitors of similar size, shape, and charge. The fundamental principles guiding the molecular recognition, such as self-assembly and complementarity, have inspired the development of biomimetic receptors. In the current work, we report a self-assembled triple anion helicate (host 2) featuring a cavity resembling that of the choline-binding protein ChoX, as revealed by crystal and density functional theory (DFT)-optimized structures, which binds choline in a unique dual-site-binding mode. This similarity in structure leads to a similarly high selectivity of host 2 for choline over its derivatives, as demonstrated by the NMR and fluorescence competition experiments. Furthermore, host 2 is able to act as a fluorescence displacement sensor for discriminating choline, acetylcholine, l-carnitine, and glycine betaine effectively.

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Section: Introductionmentioning

confidence: 99%

Selective binding of choline by a phosphate-coordination-based triple helicate featuring an aromatic box

et al. 2017

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“…Therefore, to gain insight into the host-guest binding modes, various NMR studies were performed on the diamagnetic yttrium(III) analogue, YL. 18 High-resolution 1 H NMR spectra were recorded with YL in the presence of 20 equiv. of Glu or HCO 3 À (Fig.…”

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A low-molecular-weight ditopic MRI probe for ratiometric sensing of zwitterionic amino acid neurotransmitters

Toljić

Angelovski

2019

Chem. Commun.

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We report a novel ditopic Gd(III)-based probe selective to zwitterionic amino acid neurotransmitters (ZNTs) crafted for ratiometric MRI imaging. The probe displayed increased binding affinity to ZNTs and non-synchronized concentration-dependent changes of the r 1 -and r 2 -relaxivity. Through the application of a T 2 /T 1 weighted MRI strategy, we demonstrated signal enhancement for cooperatively bound glutamate and c-aminobutyric acid ZNTs over competitive hydrogencarbonate, which remained MR silent.A wide variety of neuronal diseases are characterized by the overexpression of zwitterionic amino acid neurotransmitters (ZNTs) into the synaptic cleft, which in abnormal amounts trigger a plethora of processes resulting in the partial impairment or death of nerve cells. 1 Excess secretion of the major excitatory glutamate (Glu) or inhibitory g-aminobutyric acid (GABA) ZNTs causes an imbalance in the excitation level of the brain, leading to various diseases, such as epileptic seizures that result in the degeneration of neuronal tissue. Thus, decoding the spatiotemporal patterns of brain chemodynamics could imply connection with related diseases. For this reason, ZNTs are recognized as irreplaceable biomarkers for monitoring neuronal activity. Currently, non-invasive imaging techniques based on magnetic resonance (MR), i.e. diamagnetic chemical exchange saturation transfer (diaCEST) or 13 C MR spectroscopy, are preferably used due to good spatio-temporal resolution and depth of penetration. However, they do not distinguish between intra-and extracellular concentration of ZNTs, and have insufficient chemical resolution and low sensitivity. 2,3 A promising way to address these issues involves the introduction of a paramagnetic sensor capable of altering image contrast upon interaction with the target metabolite. 4 Therefore, the development of MR imaging (MRI) probes responsive to extracellular ZNTs is of emerging importance.Molecular recognition between magnetic host sensors and guest molecules occurs via the formation of a ternary adduct, and is evaluated via its binding affinity. In the case of a 'turn-off' response, the interaction of biomarkers with the coordination cage of an MRI probe restricts inner-sphere water accessibility to the paramagnetic center resulting in a signal decrease. 5 So far, the direct sensing of NTs has been approached with two distinct designs, via genetically engineered metalloproteins and by small-molecule ditopic paramagnetic probes. 6-8 Although large molecule CAs tailored for monoamine neurotransmitters were shown to be capable of detecting target metabolites in the mM range, further improvement of small-sized probes is imperative due to issues associated with translation into biological systems. In terms of host-guest interaction, the low-molecular-weight sensors are bismacrocyclic Gd(III)-based complexes with a 1,4,7,10tetraazacyclododecane-1,7-dicarboxylic acid (DO2A) chelator, whose geometry allows for easy access to small anions. 9 In particular, the selectivity of the current sen...

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“…[16,17] In the cone conformation, the tetra-a-isomers feature adeep aromatic cavity that is open at one end and closed at the opposite one by four pyrrole NH moieties.W ea lso reported the installation of bridging polar phosphonate groups at the upper rim of phenoxy tetra-a-calix [4]pyrroles. [18,19] Simple molecular-modelling studies predicted that the neutral creatinine tautomer 2 would be ap erfect fit in terms of size and hydrogen-bonding complementarity to the polar aromatic cavity offered by monophosphonate-bridged cavitand 1. Receptor 1 was prepared starting from apreviously reported aryl-extended tetrol calix [4]pyrrole.…”

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Recognition and Sensing of Creatinine

et al. 2016

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Current methods for creatinine quantification suffer from significant drawbacks when aiming to combine accuracy, simplicity,and affordability.Here,anunprecedented synthetic receptor,a na ryl-substituted calix [4]pyrrole with am onophosphonate bridge,i sr eported that displays remarkable affinity for creatinine and the creatininium cation. The receptor works by including the guest in its deep and polar aromatic cavity and establishing directional interactions in three dimensions.When incorporated into asuitable polymeric membrane, this molecule acts as an ionophore.Ahighly sensitive and selective potentiometric sensor suitable for the determination of creatinine levels in biological fluids,such as urine or plasma, in an accurate,f ast, simple,a nd cost-effective way has thus been developed.Considering the importance of creatinine levels with respect to human health, the methods that are currently available for its quantification are surprisingly suboptimal. Them ost widely used approach is based on the JaffØ method,[1] which was developed more than 100 years ago,a nd is rather complex, tedious,a nd suffers from problems with interference.[2] Alternative enzyme-based assays with either colorimetric or electrochemical detection have become more common during the last decades and have overcome many issues,b ut still show analytical and practical weaknesses. [3] Highly accurate results are obtained by using isotope-dilution gas chromatography mass spectrometry (ID-GC-MS). Unfortunately,t his approach cannot be applied in ah ightraffic routine laboratory. [4,5] In the mid 1990s,supramolecular approaches for the recognition of creatinine began to appear.Thed esigned synthetic receptors comprised an edge functionalized with convergent hydrogen-bonding sites that were complementary to creatinine. [6][7][8][9][10][11] On the other hand, ionselective electrodes (ISEs) are among the simplest and most robust gauges of ion concentration that are already in use in routine clinical laboratories.[12] Thekey hurdle in the development of ISEs for relatively complex analytes,s uch as creatinine,i st he availability of "ionophores", synthetic receptors that preferentially bind the target molecule. [13] Ionophores are responsible for an increase in ISE sensitivity and selectivity.T ot he best of our knowledge,t here are only two examples of neutral synthetic ionophores that are used in the potentiometric analysis of creatinine levels. [14,15] Unfortunately,t he resulting ISEs did not exhibit selectivities and detection limits suitable for the analysis of biological samples.Herein, we introduce an ovel ISE that is suitable for the simple and accurate determination of creatinine levels in body fluids.T his ISE hinges on anovel calix[4]pyrrole-based ionophore, 1,w hich has as trong affinity towards creatinine (2)and the creatinine cation 2·H + (Figure 1). In contrast to its synthetic flat ("two-dimensional") predecessors, [6][7][8][9][10][11] receptor 1 has at hree-dimensional shape and includes the creatinine guest 2 in its ar...

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Tetra-phosphonate Calix[4]pyrrole Cavitands as Multitopic Receptors for the Recognition of Ion Pairs

Cited by 60 publications

References 31 publications

Selective binding of choline by a phosphate-coordination-based triple helicate featuring an aromatic box

Selective binding of choline by a phosphate-coordination-based triple helicate featuring an aromatic box

A low-molecular-weight ditopic MRI probe for ratiometric sensing of zwitterionic amino acid neurotransmitters

Recognition and Sensing of Creatinine

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