Squaramide-based receptors in anion supramolecular chemistry: insights into anion binding, sensing, transport and extraction.

Over the last 15 years, squaramide-based receptors have attracted the attention of supramolecular chemists working in the field of anion recognition. Herein, we highlight examples of squaramide-based receptors that are able to bind, sense, extract and transport anions.

Fluorescent sensing of non-steroidal anti-inflammatory drugs naproxen and ketoprofen by dansylated squaramide-based receptors.

Bis-squaramide receptors L1-L4 bearing a dansyl moiety were synthesised and their potential applications as fluorescent probes towards non steroidal anti-inflammatory drugs naproxen and ketoprofen was investigated. A detailed photophysical characterization in CH3CN/DMSO solution (9 : 1 v/v) was conducted and demonstrated that the two macrocyclic receptors L1 and L2 show good sensitivity towards ketoprofen with an ON-OFF fluorescent response, while the two open chain receptors L3 and L4 behave similarly with the three guests considered. DFT theoretical calculations carried out on L2 and L4 as model receptors allowed to propose a possible coordination mode towards the guests. Finally, 1H-NMR spectroscopy in DMSO-d6/0.5% water solution demonstrated that the four receptors interact with the considered guests via H-bonds.

Role of the Solvent in the Reactivity of Bis-4-imidazoline-2-selone Derivatives toward I2: An Experimental and Theoretical Approach.

The reactivity of 1,1'-bis(3-methyl-4-imidazolin-2-selone)methane (L1) and 1,2-bis(3-methyl-4-imidazolin-2-selone)ethane (L2) toward I2 has been explored in MeCN under different experimental conditions and compared with that in CH2Cl2. The compounds [L1'](I)2 (I), [L1I]n(I)n (II), [L1(µ-Se)](I)2·1/2H2O (III), [L1I](I3)·2I2 (IV), and [L2](I)2·MeCN (V) were obtained and characterized. X-ray diffraction analyses point out an ionic nature for these compounds, which is presumably favored by the polarity of the solvent used. In particular, [L1I]n(I)n (II) represents the first example of an iodonium complex of imidazoline-2-selone derivatives, while [L1(µ-Se)](I)2·1/2H2O (III) represents a unique example of a dicationic [RSeSeSeR] triselane. Density functional theory calculations have allowed us to better understand the nature of the obtained compounds and to justify their formations in polarizing reaction conditions rather than in low polar solvents.

The role of indolyl substituents in squaramide-based anionophores.

A new family of squaramide-based anionophores (L1-L8) have been synthesised and fully characterised with the aim to investigate the effect of indolyl substituents on their anion binding and transmembrane transport properties. L1, L2, L6, and L8, bearing a 7-indolyl/indol-7-yl moiety as the substituent, were found to be the most efficient of the series in binding chloride with high stability constants. L1, L6, and L8 were also found to be the most potent anionophores of the series, able to mediate transmembrane anion transport. In particular, L6 bearing the 3,5-bis(trifluoromethyl)phenyl group was found to be the most active transporter, and its efficiency as an anionophore/anion transporter was favourably compared with that of their symmetrically-substituted squaramide analogues L9 and L10, previously reported in the literature.

Supramolecular self-associating amphiphiles: determination of molecular self-association properties and calculation of critical micelle concentration using a high-throughput, optical density based methodology.

Supramolecular self-associating amphiphiles are a class of amphiphilic salt, the anionic component of which is 'frustrated' in nature, meaning multiple hydrogen bonding modes can be accessed simultaneously. Here we derive critical micelle concentration values for four supramolecular self-associating amphiphiles using the standard pendant drop approach and present a new high-throughput, optical density measurement based methodology, to enable the estimation of critical micelle concentrations over multiple temperatures. In addition, we characterise the low-level hydrogen bonded self-association events in the solid state, through single crystal X-ray diffraction, and in polar organic DMSO-d6 solutions using a combination of 1H NMR techniques. Moving into aqueous ethanol solutions (EtOH/H2O or EtOH/D2O (1 : 19 v/v)), we also show these amphiphilic compounds to form higher-order self-associated species through a combination of 1H NMR, dynamic light scattering and zeta potential studies.

Advances in applied supramolecular technologies.

Supramolecular chemistry is a comparatively young field that to date has mainly been focused on building a foundation of fundamental understanding. With much progress in this area, researchers are seeking to apply this knowledge to the development of commercially viable products. In this review we seek to outline historical and recent developments within the field of supramolecular chemistry that have made the transition from laboratory to market, and to bring to light those technologies that we believe have commercial potential. In doing so we hope we may illuminate pathways to market for research currently being conducted.

Anion-Responsive Fluorescent Supramolecular Gels.

Three novel bis-urea fluorescent low-molecular-weight gelators (LMWGs) based on the tetraethyl diphenylmethane spacer-namely, L1, L2, and L3, bearing indole, dansyl, and quinoline units as fluorogenic fragments, respectively, are able to form gel in different solvents. L2 and L3 gel in apolar solvents such as chlorobenzene and nitrobenzene. Gelator L1 is able to gel in the polar solvent mixture DMSO/H2O (H2O 15% v/v). This allowed the study of gel formation in the presence of anions as a third component. An interesting anion-dependent gel formation was observed with fluoride and benzoate inhibiting the gelation process and H2PO4-, thus causing a delay of 24 h in the gel formation. The interaction of L1 with the anions in solution was clarified by 1H-NMR titrations and the differences in the cooperativity of the two types of NH H-bond donor groups (one indole NH and two urea NHs) on L1 when binding BzO- or H2PO4- were taken into account to explain the inhibition of the gelation in the presence of BzO-. DFT calculations corroborate this hypothesis and, more importantly, demonstrate considering a trimeric model of the L1 gel that BzO- favours its disruption into monomers inhibiting the gel formation.

Can Serendipity Still Hold Any Surprises in the Coordination Chemistry of Mixed-Donor Macrocyclic Ligands? The Case Study of Pyridine-Containing 12-Membered Macrocycles and Platinum Group Metal Ions PdII, PtII, and RhIII.

This study investigates the coordination chemistry of the tetradentate pyridine-containing 12-membered macrocycles L1-L3 towards Platinum Group metal ions PdII, PtII, and RhIII. The reactions between the chloride salts of these metal ions and the three ligands in MeCN/H2O or MeOH/H2O (1:1 v/v) are shown, and the isolated solid compounds are characterized, where possible, by mass spectroscopy and 1H- and 13C-NMR spectroscopic measurements. Structural characterization of the 1:1 metal-to-ligand complexes [Pd(L1)Cl]2[Pd2Cl6], [Pt(L1)Cl](BF4), [Rh(L1)Cl2](PF6), and [Rh(L3)Cl2](BF4)·MeCN shows the coordinated macrocyclic ligands adopting a folded conformation, and occupying four coordination sites of a distorted square-based pyramidal and octahedral coordination environment for the PdII/PtII, and RhIII complexes, respectively. The remaining coordination site(s) are occupied by chlorido ligands. The reaction of L3 with PtCl2 in MeCN/H2O gave by serendipity the complex [Pt(L3)(m-1,3-MeCONH)PtCl(MeCN)](BF4)2·H2O, in which two metal centers are bridged by an amidate ligand at a Pt1-Pt2 distance of 2.5798(3) Å and feature one square-planar and one octahedral coordination environment. Density Functional Theory (DFT) calculations, which utilize the broken symmetry approach (DFT-BS), indicate a singlet d8-d8 PtII-PtII ground-state nature for this compound, rather than the alleged d9-d7 PtI-PtIII mixed-valence character reported for related dinuclear Pt-complexes.

Switching-On Fluorescence by Copper (II) and Basic Anions: A Case Study with a Pyrene-Functionalized Squaramide.

The new symmetric acyclic N,N'-bis(1-pyrenyl) squaramide (H2L) functionalized with the pyrene moiety as a fluorogenic fragment has been designed and its ability to selectively detect specific anions and metals investigated. H2L selectively binds Cl- both in solution (DMSO 0.5% H2O and MeCN) and in the solid state, and allows to selectively detect Cu2+ in MeCN with the formation of a 2:1 metal-receptor complex, with a green intense emission appreciable by naked eye under the UV lamp. The H2L copper complex preserves its emission properties in the presence of Cl-. The addition of basic anions (OH-, CN-, and F-) up to 10 equivalents caused the deprotonation of the squaramide NHs and a dramatic change of the emission properties of the H2L copper complex.

An Area-Specific, International Community-Led Approach to Understanding and Addressing Equality, Diversity, and Inclusion Issues within Supramolecular Chemistry.

Diversity, equality, and inclusion (DEI/EDI) are pressing issues in chemistry and the natural sciences. In this Essay we share how an area-specific approach is "calling in" the community so that it can act to address EDI issues, and support those who are marginalised. Women In Supramolecular Chemistry (WISC) is an international network that aims to support equality, diversity, and inclusion within supramolecular chemistry. WISC has taken a field-specific approach using qualitative research methods with scientists to identify the support that is needed and the problems the supramolecular community needs to address. Herein, we present survey data from the community which highlight the barriers that are faced by those who take career breaks for any reason, a common example is maternity leave, and the importance of mentoring to aid progression post-PhD. In conclusion, we set out an interdisciplinary and creative approach to addressing EDI issues within supramolecular chemistry.

Multifunctional cubic liquid crystalline nanoparticles for chemo- and photodynamic synergistic cancer therapy.

With the aim of engineering multifunctional nanoparticles useful for cancer therapy, a diketopyrrolopyrrole-porphyrin based photosensitizer was here conjugated to a block copolymer (Pluronic F108), and used to stabilize in water lipidic cubic liquid crystalline nanoparticles (cubosomes), also loaded with the antineoplastic agent docetaxel. The physicochemical characterization by SAXS, DLS, and cryo-TEM demonstrated that the formulation consisted of cubosomes, about 150 nm in size, possessing a bicontinuous cubic structure (space group Pn3m). The cellular imaging experiments proved that these nanoparticles localized in lysosomes and mitochondria, while cytotoxicity tests evidenced a slight but significant synergistic effect which, after irradiation, increased the toxicity induced by docetaxel alone, allowing further reduction of cell viability.

Diradical Character of Neutral Heteroleptic Bis(1,2-dithiolene) Metal Complexes: Case Study of [Pd(Me2timdt)(mnt)] (Me2timdt = 1,3-Dimethyl-2,4,5-trithioxoimidazolidine; mnt2- = 1,2-Dicyano-1,2-ethylenedithiolate).

The reaction of the bis(1,2-dithiolene) complex [Pd(Me2timdt)2] (1; Me2timdt•- = monoreduced 1,3-dimethyl-2,4,5-trithioxoimidazolidine) with Br2 yielded the complex [Pd(Me2timdt)Br2] (2), which was reacted with Na2mnt (mnt2- = 1,2-dicyano-1,2-ethylenedithiolate) to give the neutral mixed-ligand complex [Pd(Me2timdt)(mnt)] (3). Complex 3 shows an intense solvatochromic near-infrared (NIR) absorption band falling between 955 nm in DMF and 1060 nm in CHCl3 (ε = 10700 M-1 cm-1 in CHCl3). DFT calculations were used to elucidate the electronic structure of complex 3 and to compare it with those of the corresponding homoleptic complexes 1 and [Pd(mnt)2] (4). An in-depth comparison of calculated and experimental structural and vis-NIR spectroscopic properties, supported by IEF-PCM TD-DFT and NBO calculations, clearly points to a description of 3 as a dithione-dithiolato complex. For the first time, a broken-symmetry (BS) procedure for the evaluation of the singlet diradical character (DC) of heteroleptic bis(1,2-dithiolene) complexes has been developed and applied to complex 3. The DC, predominant for 1 (nDC = 55.4%), provides a remarkable contribution to the electronic structures of the ground states of both 3 and 4, showing a diradicaloid nature (nDC = 24.9% and 27.5%, respectively). The computational approach developed here clearly shows that a rational design of the DC of bis(1,2-ditiolene) metal complexes, and hence their linear and nonlinear optical properties, can be achieved by a proper choice of the 1,2-dithiolene ligands based on their electronic structure.

Heavy metal tolerance of orchid populations growing on abandoned mine tailings: A case study in Sardinia Island (Italy).

Understanding how environmental pollutants influence plant occurrence, growth, and development is key for effective management plans and potential bioremediation. Rare plants, such as orchids, may occur in modified habitats and on soils containing heavy metals, yet their ecological and physiological responses to heavy metals is poorly understood. We investigated the influence of heavy metal pollution on orchid growth rates and interactions with soil fungal mutualists by comparing a large population of the orchid Epipactis helleborine (L.) Crantz subsp. tremolsii (Pau) E. Klein that grows on mine tailings in south-west Sardinia (Italy) with a population that grows on non-contaminated soils in central Sardinia. Soils of the contaminated site had high levels of heavy metals and low organic matter and nutritive elements content. We performed a morphological analysis on twenty individuals that have been subjected to measurement of bioaccumulation and translocation of heavy metals. Fungi associated with the roots of plants from the contaminated and uncontaminated site were grown and identified by DNA barcoding approach. Plants from the contaminated site were smaller than the ones growing in the uncontaminated site and were found to be able to tolerate heavy metals from the soil and to accumulate and translocate them into their organs. Fungi belonging to the genus Ilyonectria (Ascomycota) were found both in contaminated and uncontaminated sites, while an unidentified fungus was isolated from roots in the contaminated site only. These results are discussed in terms of orchids' tolerance to heavy metals and its physiological and ecological mechanisms. The role of contaminated habitats in harbouring orchids and peculiar taxa is also discussed.

Cubosomes for in vivo fluorescence lifetime imaging.

Herein we provided the first proof of principle for in vivo fluorescence optical imaging application using monoolein-based cubosomes in a healthy mouse animal model. This formulation, administered at a non-cytotoxic concentration, was capable of providing both exogenous contrast for NIR fluorescence imaging with very high efficiency and chemospecific information upon lifetime analysis. Time-resolved measurements of fluorescence after the intravenous injection of cubosomes revealed that the dye rapidly accumulated mainly in the liver, while lifetimes profiles obtained in vivo allowed for discriminating between free dye or dye embedded within the cubosome nanostructure after injection.

Anion sensing by small molecules and molecular ensembles.

This Tutorial Review provides a short survey of anion sensing by small molecule anion receptors, molecular ensembles and chemodosimeters. The review highlights the many different mechanisms and approaches employed by supramolecular chemists for anion sensing and the wide structural variety present in these systems.

Silica-based nanoparticles: a versatile tool for the development of efficient imaging agents.

This review describes the recent advances in the development of imaging agents based on silica nanoparticles. Different techniques (magnetic resonance imaging, optical imaging, positron emission tomography, X-ray computed tomography, and ultrasound imaging) are described as well as the possibility of combining together different imaging techniques in the same nanoplatform and simultaneously performing imaging and therapy.

Docetaxel-Loaded Fluorescent Liquid-Crystalline Nanoparticles for Cancer Theranostics.

Here, we describe a novel monoolein-based cubosome formulation engineered for possible theranostic applications in oncology. The Docetaxel-loaded nanoparticles were stabilized in water by a mixture of commercial Pluronic (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer) F108 (PF108) and rhodamine- and folate-conjugated PF108 so that the nanoparticles possess targeting, therapeutic, and imaging properties. Nanoparticles were investigated by DLS, cryo-TEM, and SAXS to confirm their structural features. The fluorescent emission characterization of the proposed formulation indicated that the rhodamine conjugated to the PF108 experiences an environment less polar than water (similar to chloroform), suggesting that the fluorescent fragment is buried within the poly(ethylene oxide) corona surrounding the nanoparticle. Furthermore, these nanoparticles were successfully used to image living HeLa cells and demonstrated a significant short-term (4 h incubation) cytotoxicity effect against these cancer cells. Furthermore, given their analogy as nanocarriers for molecules of pharmaceutical interest and to better stress the singularities of these bicontinuous cubic nanoparticles, we also quantitatively evaluated the differences between cubosomes and multilamellar liposomes in terms of surface area and hydrophobic volume.

Cancer-cell-targeted theranostic cubosomes.

This work was devoted to the development of a new type of lipid-based (cubosome) theranostic nanoparticle able to simultaneously host camptothecin, a potent anticancer drug, and a squarain-based NIR-emitting fluorescent probe. Furthermore, to confer targeting abilities on these nanoparticles, they were dispersed using mixtures of Pluronic F108 and folate-conjugated Pluronic F108 in appropriate ratios. The physicochemical characterization, performed via SAXS, DLS, and cryo-TEM techniques, proved that aqueous dispersions of such cubosomes can be effectively prepared, while the photophysical characterization demonstrated that these nanoparticles may be used for in vivo imaging purposes. The superior ability of these innovative nanoparticles in targeting cancer cells was emphasized by investigating the lipid droplet alterations induced in HeLa cells upon exposure to targeted and nontargeted cubosomes.

Crystal structure of 4,4'-(disulfanedi-yl)dipyridinium chloride triiodide.

4,4'-(Disulfanedi-yl)dipyridinium chloride triiodide, C10H10N2S2 2+·Cl-·I3 -, (1) was synthesized by reaction of 4,4'-di-pyridyl-disulfide with ICl in a 1:1 molar ratio in di-chloro-methane solution. The structural characterization of 1 by SC-XRD analysis was supported by elemental analysis, FT-IR, and FT-Raman spectroscopic measurements.

Multimodal use of new coumarin-based fluorescent chemosensors: towards highly selective optical sensors for Hg(2+) probing.

Despite several types of fluorescent sensing molecules have been proposed and examined to signal Hg(2+) ion binding, the development of fluorescence-based devices for in-field Hg(2+) detection and screening in environmental and industrial samples is still a challenging task. Herein, we report the synthesis and characterization of three new coumarin-based fluorescent chemosensors featuring mixed thia/aza macrocyclic framework as receptors units, that is, ligands L1-L3. These probes revealed an OFF-ON selective response to the presence of Hg(2+) ions in MeCN/H2 O 4:1 (v/v), which allowed imaging of this metal ion in Cos-7 cells in vitro. Once included in silica core-polyethylene glycol (PEG) shell nanoparticles or supported on polyvinyl chloride (PVC)-based polymeric membranes, ligands L1-L3 can also selectively sense Hg(2+) ions in pure water. In particular we have developed an optical sensing array tacking advantage of the fluorescent properties of ligand L3 and based on the computer screen photo assisted technique (CSPT). In the device ligand L3 is dispersed into PVC membranes and it quantitatively responds to Hg(2+) ions in natural water samples.