The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small series of thiosquaramides was synthesised and their pH-dependent chloride binding and anion transport behaviour was investigated using 1H NMR titrations, single crystal X-ray diffraction and a variety of vesicle-based techniques. Spectrophotometric titrations and DFT calculations revealed that the thiosquaramides are significantly more acidic than their oxosquaramide analogues, with pKa values between 4.0 and 9.0. This led to the observation that at pH 7.2 the anion transport ability of the thiosquaramides is fully switched OFF due to deprotonation of the receptor, but is completely switched ON at lower pH.

This review covers recent advances in the use of the squaramide moiety in chemical research. We focus on the varied applications of squaramides under the broad headings of self-assembly, organocatalysis, molecular recognition, medicinal chemistry, and bioconjugation and highlight several examples of each application.

Macrocyclic squaramide derivatives bind sulfate ions with high selectivity and affinity in aqueous mixtures.

ABSTRACT:The synthesis and photophysical and biological investigation of Ru(II)-polypyridyl stabilized watersoluble, luminescent gold nanoparticles (AuNPs) are described. These structures bind to DNA and undergo rapid cellular uptake, being localized within the cell cytoplasm and nucleus within 4 h. T he development of functional supramolecular nanostructures for applications in photonics, 1 sensing, 2 catalysis 3 and medicine, 4 etc. is a fast emerging interdisciplinary research field. The design and synthesis of nanoparticles 5 and, in particular, functionalized gold nanoparticles (AuNPs) has been at the forefront of this effort in recent times, with many examples being developed for use in biological and medical applications, 6 due to their biocompatibility, unique size-and shape-dependence, and optoelectronic properties. Similarly, Ru(II)-polypyridyl complexes have been intensively studied due to their photophysical properties, 7 where they have been employed for example in luminescent recognition and sensing, 8 as sensitive and structurespecific DNA probes.9 Luminescent d 6 transition metal ion complexes have often been proposed as useful fluorophores for cellular imaging, 10,11 but until very recently their use in actual applications has remained scarce. With our interest in the development of luminescent novel cellular targeting (therapeutic/ imaging) agents 7a,b,12 and surface modified AuNPs, 13 we envisaged that the combination of Ru(II)-polypyridyl complexes, spatially separated from the surface of AuNPs, by a covalent spacer, could be employed as luminescent probes/imaging agents for various biological applications.15 Herein we describe the synthesis of the Ru(II) complexes 1À3, Figure 1, all of which possess a terminal alkyl thiol group which facilitates their adsorption onto AuNPs, leading to the formation of the three water-soluble systems AuNP-1, AuNP-2 and AuNP-3 (Figure 1). We demonstrate that these luminescent AuNPs offer attractive photophysical properties, ideal for application in cellular imaging, which we demonstrate using HeLa cells. These are, to the best of our knowledge, the first examples of such Ru(II)-polypyridyl functionalized AuNPs to be employed for such cellular applications.The syntheses of 1, 2, and 3 are shown in Scheme S1 (see also full details in Supporting Information) and were achieved in a few steps. The common ligand for all of these complexes is 4, the synthesis of which was achieved by employing peptidic (carbodiimide) coupling of 11-mercaptoundecanoic acid 14a with 5-amino,-1,10 phenanthroline in CH 2 Cl 2 , yielding 4 as an offwhite solid in 78% yield. The microwave irradiation of 4 in the presence of the Ru(II) bispolypyridyl dichlorides Ru(bpy) 2 Cl 2 , Ru(phen) 2 Cl 2 , and Ru(TAP) 2 Cl 2 gave 1, 2, and 3, respectively, after 40 min.14b These were isolated, by precipitation from water, using excess NH 4 PF 6 , followed by purification using automatic column chromatography [flash silica; 40:4:1 CH 3 CN/H 2 O/ NaNO 3 (sat)], yielding 1À3 in 75%, 65%, and 54%, respec...

The synthesis and photophysical properties of four squaramide based fluorescent anion sensors (1À4) are described. These luminescent compounds showed selectivity for Cl À over various other anions with concomitant changes in both their UV/visible and fluorescence properties upon Cl À addition, attributed to initial H-bonding followed by NH deprotonation in the presence of excess Cl À , signaled by a color change. The nature of the electron withdrawing aryl substituents is directly related to the H-bonding ability/acidity of the squaramide protons and can be used to tune the deprotonation behavior.Colorimetric and luminescent sensors provide a visual method for detection of a wide range of chemical species. Substantial effort has recently been invested in the synthesis of such chemosensors for detection of anions in many diverse areas including biology, industry, and the environment. 1À3 In particular, the design of charge neutral sensors capable of binding anions in competitive media, where the spectroscopic properties arising from the sensors, e.g. a color change, are modulated by addition of the external analyte has become a popular method of sensing chemical species. 4 Anion recognition has been successfully achieved through the use of numerous neutral receptors including imidazoles,