Publications

There is a growing need for workers with STEM-aligned training in the modern global economy, but a paucity of workers to fill these positions. One important contributor to this issue is low student persistence in STEM. Nontraditional science courses that utilize more active-participation and learning are attractive as tools to increase student persistence and engender more interest in STEM. Herein is described the content and implementation of the undergraduate chemistry-based service-learning course, Chemistry 1898: Service Learning, that was offered in Spring 2019 at Tulane University. The goal of the course was to increase self-efficacy in chemistry and sustain undergraduate interest in STEM. The course also serves to increase STEM interest in the New Orleans public-school students. Chemistry 1898 features a well-rounded curriculum and diverse activities. The enrolled undergraduate students were not only taught chemistry concepts (general chemistry and supramolecular chemistry) but also asked to present the chemical concepts using attention-grabbing demonstrations to public-school students in the New Orleans area. In addition, the course covered multiple nonscience topics, including the pedagogy of service-learning, background on the New Orleans public-school system, and a guide for how to work with the community. The course also involved student reflection activities/surveys and interfaced with the Tulane Center for Public Service. Preliminary qualitative results from a set of anonymous pre- and poststudent surveys indicated that the undergraduate students gained self-efficacy in the general chemistry concepts covered in the course. Although the course did not have an effect on the career choices of the undergraduate students, the majority of the students were already very interested in a STEM career. Further, some students mentioned gaining a benefit in public speaking skills, and some considered the possibility of teaching and working with children in the future.

Modular allosteric aptamers with discrete recognition and signaling regions provide a facile method of carrying out label-free detection by forgoing complex target labeling requirements. Herein, we describe the design and function of an aptamer scaffold capable of forming a hairpin loop in the presence of FAD (the signaling trigger). The aptamer includes a recognition region for the microRNA (miR) Let-7i. Upon selective miR hybridization, the aptamer undergoes a conformational shift to release FAD and thus produce a measurable response. As a result, the described method can sensitively and selectively detect miR Let-7i with a wide linear range of 0.1 pM to 1 μM and a detection limit of 150 fM. Additionally, this strategy was able to selectively discriminate between sequences with 1- and 2-nucleotide (nt) differences.

The recent discovery of ultra-high binding affinities in cucurbit[7]uril (CB7)-based host–guest pairs in an aqueous environment has rendered CB7 a rather attractive material in analytical and biomedical applications. Due to the lack of a molecular platform that can follow the same host–guest complex during repetitive mechanical measurements, however, mechanical stabilities of the CB7 system have not been revealed, hindering its potential to rival widely used conjugation pairs, such as streptavidin–biotin. Here, we assembled a DNA template in which a flexible DNA linker was exploited to keep the host (CB7) and guest (adamantane) in proximity. This platform not only increased the efficiency of the single-molecule characterization in optical tweezers but also clearly revealed mechanical features of the same host–guest complex. We found that positively charged adamantane guest demonstrated higher mechanical stability (49 pN) than neutral adamantane (44 pN), a trend consistent with the chemical affinity between guest molecules and the CB7 host. Surprisingly, we found that a hexyl group adjacent to the adamantane served as a chaperone to assist the formation of the adamantane–CB7 pairs. The discovery of an unprecedented chaperone-assisted interaction mechanism provides new approaches to efficiently assemble host–guest-based supramolecules with increased mechanical stabilities, which can be exploited in various biomedical, biosensing, and materials fields.

The intricate arrangement of numerous and closely placed chromophores on nanoscale scaffolds can lead to key photonic applications ranging from optical waveguides and antennas to signal-enhanced fluorescent sensors. In this regard, the self-assembly of dye-appended DNA sequences into programmed photonic architectures is promising. However, the dense packing of dyes can result in not only compromised DNA assembly (leading to ill-defined structures and precipitates) but also to essentially nonfluorescent systems (due to π–π aggregation). Here, we introduce a two-step “tether and mask” strategy wherein large porphyrin dyes are first attached to short G-quadruplex-forming sequences and then reacted with per-O-methylated β-cyclodextrin (PMβCD) caps, to form supramolecular synthons featuring the porphyrin fluor fixed into a masked porphyrin lantern (PL) state, due to intramolecular host–guest interactions in water. The PL–DNA sequences can then be self-assembled into cyclic architectures or unprecedented G-wires tethered with hundreds of porphyrin dyes. Importantly, despite the closely arrayed PL units (∼2 nm), the dyes behave as bright chromophores (up to 180-fold brighter than the analogues lacking the PMβCD masks). Since other self-assembling scaffolds, dyes, and host molecules can be used in this modular approach, this work lays out a general strategy for the bottom-up aqueous self-assembly of bright nanomaterials containing densely packed dyes.

Transport of vibrational energy via linear alkyl molecular chains can occur efficiently and with a high speed. This study addresses the question of how such transport is changed if an amide group is incorporated in the middle of such chain. A set of four compounds, Amn-4, was synthesized such that an amide group is connected to two alkyl chains. The alkyl chain on one side of the amide, featuring 4, 7, 11, or 15 CH₂ units, is terminated by an azido group, while the alkyl chain on another side is of fixed length with four methylene groups terminated with a methyl ester group. The energy transport in Amn-4 in CD₃CN solution, measured by relaxation-assisted two-dimensional infrared spectroscopy, was initiated and recorded using various combinations of tags and reporters, which included N₃ and C═O stretching modes of the end groups and amide-I and amide-II modes at the amide. It was found that the transport initiated by the amide-I mode in the alkyl chain attached to C═O side of the amide proceeds with a constant speed of 4.2 Å/ps, supported by the CH₂ rocking band of the chain. The end group-to-end group energy transport times for compounds with uneven alkyl chain length fragments appears to be additive. The transport from either end group of the molecule started as ballistic transport. The passage through the amide was found to be governed by intramolecular vibrational relaxation steps. After it passed the amide group, the transport was found to occur with constant but different speeds, dependent on the passage direction. The transport toward the ester was found to occur with the speed of 4.2 Å/ps, similar to that for the amide-I mode initiation and supported by the CH₂ rocking band. The transport toward the azido group occurred with the speed of 8.0 Å/ps, which matches the speed supported by the CC stretching band. The results suggest that, after the C═O group initiation, the excess energy reaches the amide group ballistically, redistributes at the amide, and reforms a wavepacket, which propagates further with a high speed of 8 Å/ps. This observation opens opportunities of controlling the energy transport process in molecules by affecting the alien group via specific interactions, including hydrogen bonding.

With this Feature Article we review, for the first time, the development of DNA–host conjugates—a nascent yet rapidly growing research focus within the ambit of DNA supramolecular chemistry. Synthetic hosts (such as cyclodextrins, cucurbiturils, and calixarenes) are well-suited to be partnered with DNA, since DNA assembly and host–guest binding both thrive in aqueous media, are largely orthogonal, and exhibit controllable and input-responsive properties. The covalent braiding of these two supramolecular synthons thus leads to advanced self-assemblies and nanostructures with exciting function that range from drug delivery agents to input-triggered switches. The latter class of DNA–host conjugates have been demonstrated to precisely control protein activity, and have also been used as modulable catalysts and versatile biosensors.

A series of water-soluble fluorescent perylene dyes (perylenemonoimides PMI1, PMI2, and PMI3) with two aromatic binding units (a perylene-core and a phenyl group) as guest molecules for binding with cucurbit[8]uril (CB8) were synthesized. The guest structure was varied by modifying the phenyl group and the spacer between the two binding units. Differences in binding, self-assembly, and optical properties of the corresponding host-guest complexes were observed. At low micromolar concentrations, a highly emissive 1:1 CB8•PMI1 complex with high binding affinity (K_a=1.5 x 10⁷ M^–1) was formed in water. Interestingly, at higher concentrations of the CB8•PMI1 complex (e. g., >10^–4 M), non-emissive self-assembled nanowires were formed. In comparison, the binding affinity of CB8•PMI2 and CB8•PMI3 was determined to be only 5.0 x 10⁵ M^–1 and 1.7 x 10⁴ M^–1, respectively. The host-guest complexes with various binding affinities could serve as fluorescent displacement probes for the detection of a range of CB8-binding guest analytes.

A test compound featuring azido and cyano end groups linked by an alkyl spacer, az-(CH₂)₁₁-CN (az11CN), was designed as a probe of mobility of synthetic lipid membrane interiors and mobility of solvents accessed via 2DIR spectral diffusion measurements. The results indicate that the az11CN compound is oriented in lipid membranes such that the azido group is well inside the membrane, while the cyano group resides in the region of moderate polarity around the carbonyl groups of the lipid. The lineshape of the azido moiety transition at 2100 cm⁻¹ shows significant broadening in nonpolar solvents such as hexane. In silico analysis demonstrated that the structural softness of the azido group, intrinsic Fermi resonance at the azido site, and broad wagging, twisting, and rocking vibrational CH₂ bands of the alkane chain result in a large number of Fermi resonances with the fundamental transition at 2100 cm⁻¹, thus providing a smooth and featureless linewidth.

Supramolecular Chemistry takes significant inspiration from nature, with common terms that populate the introduction to many original articles including biomimetic, bioinspired, and the like. This is to be expected given the diversity of structure and function prevalent in the biological playground that arises as a consequence of noncovalent structure. Thus, to replicate biology with designed synthetic systems and to intervene in biological systems should be seen as a major objective in supramolecular chemistry along the road toward the ultimate goal of creating functional architecture(s) not found in nature. The companion volume to this—Bioinspired and Biomimetic Supramolecular Chemistry—includes inter alia chapters describing the community’s efforts to reproduce biology with model systems whereas this volume—Supramolecular Medicinal Chemistry and Chemical Biology—describes the progress made in exploiting our collective knowledge of supramolecular chemistry to intervene in biological systems and/or control materials behavior through well-refined understanding of noncovalent chemistry to achieve therapeutic or diagnostic benefit.