Nanostructured Luminescent Micelles: Efficient “Functional Materials” for Sensing Nitroaromatic and Nitramine Explosives

Luminescent micelles are extensively studied molecular scaffolds used in applied supramolecular chemistry. These are particularly important due to their uniquely organized supramolecular structure and chemically responsive physical and optical features. Various luminescent tags can be incorporated with these amphiphilic micelles to create efficient luminescent probes that can be utilized as “chemical noses” (sensors) for toxic and hazardous materials, bioimaging, drug delivery and transport, etc. Due to their amphiphilic nature and well-defined reorganized self-assembled geometry, these nano-constructs are desirable candidates for size and shape complementary guest binding or sensing a specific analyte. A large number of articles describing micellar fluorogenic probes are reported, which are used for cation/anion sensing, amino acid and protein sensing, drug delivery, and chemo-sensing. However, this particular review article critically summarizes the sensing application of nitroaromatic (e.g., trinitrotoluene (TNT), trinitrobenzene (TNB), trinitrophenol (TNP), dinitrobenzene (DNB), etc.) and nitramine explosives (e.g., 1,3,5-trinitro-1,3,5-triazinane, trivially named as “research department explosive” (RDX), 1,3,5,7-tetranitro-1,3,5,7-tetrazocane, commonly known as “high melting explosive” (HMX) etc.). A deeper understanding on these self-assembled luminescent “functional materials” and the physicochemical behavior in the presence of explosive analytes might be helpful to design the next generation of smart nanomaterials for forensic applications. This review article will also provide a “state-of-the-art” coverage of research involving micellar–explosive adducts demonstrating the intermolecular charge/electron transfer (CT/ET) process operating within the host–guest systems.

Molecular Dynamic Simulation Analysis on the Inclusion Complexation of Plumbagin with β-Cyclodextrin Derivatives in Aqueous Solution

Stable encapsulation of medically active compounds can lead to longer storage life and facilitate the slow-release mechanism. In this work, the dynamic and molecular interactions between plumbagin molecule with β-cyclodextrin (BCD) and its two derivatives, which are dimethyl-β-cyclodextrin (MBCD), and 2-O-monohydroxypropyl-β-cyclodextrin (HPBCD) were investigated. Molecular dynamics simulations (MD) with GLYCAM-06 and AMBER force fields were used to simulate the inclusion complex systems under storage temperature (4 °C) in an aqueous solution. The simulation results suggested that HPBCD is the best encapsulation agent to produce stable host–guest binding with plumbagin. Moreover, the observation of the plumbagin dynamic inside the binding cavity revealed that it tends to orient the methyl group toward the wider rim of HPBCD. Therefore, HPBCD is a decent candidate for the preservation of plumbagin with a promising longer storage life and presents the opportunity to facilitate the slow-release mechanism.

A General Picture of Cucurbit[8]uril Host-Guest Binding: Recalibrating Bonded Interactions

Atomic-level understanding of the dynamical feature of host-guest interactions remains a central challenge in supramolecular chemistry. The remarkable guest binding behavior of the Cucurbiturils family of supramolecular containers makes them promising drug carriers. Among Cucurbit[n]urils, Cucurbit[8]uril (CB8) has intermediate portal size and cavity volume. It can exploit almost all host-guest recognition motifs formed by this host family. In our previous work, an extensive computational investigation of the binding of 7 commonly abused and structurally diverse drugs to the CB8 host was performed and a general dynamical binding picture of CB8-guest interactions was obtained. Further, two widely used fixed-charge models for drug-like molecules were investigated and compared in great detail, aiming at providing guidelines in choosing an appropriate charge scheme in host-guest modelling. Iterative refitting of atomic charges leads to improved binding thermodynamics and the best root-mean-squared deviation from the experimental reference is 2.6 kcal/mol. In this work, we focus on a thorough evaluation of the remaining parts of classical force fields, i.e., the bonded interactions. The widely used general Amber force fields are assessed and refitted to improve the intra-molecular conformational preference and thus the description of inter-molecular host-guest interactions. The interaction pattern and binding thermodynamics show significant dependence on the modelling parameters. The refitted system-specific parameter set improves the consistency of the modelling results and the experimental reference significantly. Finally, combining the previous charge-scheme comparison and the current force-field refitting, we provide general guidelines for the theoretical modelling of host-guest binding.

Tetraphenylethene-Embedded Pillar[5]arene and [15]Paracyclophane: Distorted Cavities and Host–Guest Binding Properties

Two aggregation-induced emission (AIE) macrocycles (DMP[5]-TPE and PCP[5]-TPE) were prepared by embedding Tetraphenylethene (TPE) unit into the skeletons of Dimethoxypillar[5]arene (DMP[5]) and [15]Paracyclophane ([15]PCP) at meso position, respectively. In crystal, the PCP[5]-TPE showed a distorted cavity, and the incubation of hexane inside the DMP[5]-TPE cavity caused a distinct change in the molecular conformation compared to PCP[5]-TPE. There was no complexation between PCP[5]-TPE and 1,4-dicyanobutane (DCB). UV absorption experiments showed the distorted cavity of DMP[5]-TPE hindered association with DCB.

Estimation of Enantiomeric Excess Based on Rapid Host–Guest Exchange

Chiral molecules possess enantiomers that have non-superimposable chemical structures but exhibit identical nuclear magnetic resonance (NMR) spectra. This feature prevents the use of NMR spectroscopic methods for the determination of enantiomeric excesses (ee) of chiral molecules, using simple mixtures of their enantiomers. Recently, however, it was reported that the addition of a symmetrical prochiral molecule (a reporter or host) into a solution of chiral analyte can lead to estimation of ee through interactions involving rapid exchange of the chiral analyte (guest) in the formed host–guest complex. This is due to the ee-dependent splitting of NMR resonances of the prochiral host molecule based on averaging the chemical shift non-equivalency caused by the presence of a chiral guest. The mechanism is not dependent on diastereomer formation, and 1:1 host–guest complexes can also show ee-dependent NMR peak splitting. Prochiral molecules capable of ee sensing using the NMR technique are now referred to as so-called prochiral solvating agents (pro-CSAs). pro-CSAs represent a family of reagents distinct from the commonly used NMR chiral derivatizing reagents (where chiral auxiliaries are used to derivatize enantiomers to diastereomers) or chiral solvating agents (where chiral auxiliaries interact in an asymmetric manner with analyte enantiomers). pro-CSA methods are unique since neither pro-CSA nor NMR contains chiral factors, making the technique neutral with respect to chirality. Here, we review our recent work on this matter involving several different nominally achiral receptor molecules whose unique guest binding properties and solution characteristics (especially with regard to NMR spectroscopy) allow for the estimation of ee in the corresponding chiral guests.

Light-gated binding in double-motorized porphyrin cages

Molecular motors change conformation under the influence of light and when attached to host molecules they may find applications as sensors and switchable catalysts. Here we present a porphyrin macrocyclic host functionalized with two motor appendages for future catalytic applications. The compound is formed as a mixture of six stereoisomers (three sets of enantiomers), which have been separated by (chiral) chromatography. 1H NMR and chiral spectroscopy revealed that in one set of diastereomers the two motors interact with the cavity of the host (bound-bound), whereas in a second set one interacts and the other one does not (bound-loose). In the third set both motors do not interact with the host compound (loose-loose). The motorized hosts bind guest molecules in the order: (loose-loose) > (bound-loose) > (bound-bound). They can be switched with light to pseudo-identical diastereomers, leading to orthogonal behavior in the light-gated binding of guest molecules. Whereas the photo-isomerization of the diastereomer set loose-loose significantly lowers the binding affinity for viologen guests, the opposite is true for the diastereomer set bound-bound, i.e. the binding affinity increases. For the diastereomer set bound-loose no influence on guest binding is observed as the effect of photoisomerization on the motors is cancelled out.