Selected Research Publications

Selected Research Publications | 85 Publications
Liu, S.; Gan, H.; Hermann, A. T.; Rick, S. W.; Gibb, B. C. Kinetic resolution of constitutional isomers controlled by selective protection inside a supramolecular nanocapsule. Nature Chemistry 2010, 2, 847-852.
Publisher's Version
The concept of self-assembling container molecules as yocto-litre reaction flasks is gaining prominence. However, the idea of using such containers as a means of protection is not well developed. Here, we illustrate this idea in the context of kinetic resolutions. Specifically, we report on the use of a water-soluble, deep-cavity cavitand to bring about kinetic resolutions within pairs of esters that otherwise cannot be resolved because they react at very similar rates. Resolution occurs because the presence of the cavitand leads to a competitive binding equilibrium in which the stronger binder primarily resides inside the host and the weaker binding ester primarily resides in the bulk hydrolytic medium. For the two families of ester examined, the observed kinetic resolutions were highest within the optimally fitting smaller esters.
Grayson, S. M.; Gibb, B. C. Dendronized cavitands: A step towards a synthetic viral capsid?. Soft Matter 2010, 6, 1377-1382.
Publisher's Version
Dendronized cavitands represent unique macromolecular hosts for encapsulation of biologically relevant guests. They combine the highly specific guest binding exhibited by deep-cavity cavitands, with the modular yet monodisperse macromolecular structure provided by dendrimers. Because these structures retain the ability to assemble into dimeric capsules, they resemble a simplified synthetic analog of viral capsids, displaying a modular, functionalizable outer coating while providing a protective cavity for a range of small-molecule payloads. This article highlights their preparation, their characterization, and their unique potential for probing in vivo drug delivery.
Sundaresan, A. K.; Kaanumalle, L. S.; Gibb, C.; Gibb, B. C.; Ramamurthy, V. Chiral photochemistry within a confined space: diastereoselective photorearrangements of a tropolone and a cyclohexadienone included in a synthetic cavitand. Dalton Transactions 2009, 4003-4011.
Publisher's Version
The value of a supramolecular assembly to enforce a closer interaction between a chiral auxiliary and a reaction center has been established using photoreactions of tropolone and cyclohexadienone derivatives. Two probe molecules utilized to establish the concept undergo 4 e− electrocyclization and oxa-di-π-methane rearrangement from excited singlet and triplet state, respectively. The chiral auxiliaries investigated here has no/little effect in acetonitrile solution during phototransformations of the probe molecules to yield products with new chiral centers. On the other hand the same ones are able to enforce diastereoselectivities to the extent of ∼30% when the reactions occur within the restricted space of a capsule made up of a synthetic cavitand commonly known as octa acid. Extensive NMR studies have been utilized to characterize the guest–host supramolecular structures. The results presented here should be of value in the overall understanding of chiral induction in photochemical reactions.
Sundaresan, A. K.; Gibb, C. L.; Gibb, B. C.; Ramamurthy, V. Chiral photochemistry in a confined space: torquoselective photoelectrocyclization of pyridones within an achiral hydrophobic capsule. Tetrahedron 2009, 65, 7277-7288.
Publisher's Version
Chiral induction during the photoelectrocyclization of pyridones included within octa acid (OA) capsule has been established. Chiral induction is brought about by a chiral auxiliary appended to the reactive pyridone moiety. Importantly, the same chiral auxiliary while ineffective in acetonitrile solution is found to be effective within the confined space of OA capsule. The diastereomeric excess of 92% obtained here is comparable only to that in solid state. OA capsule, we believe, provides restriction to the rotational motions of the reactant pyridone and chiral auxiliary and thus places the chiral auxiliary in a selective conformation with respect to the reactive pyridone part. A correlation between the position of the methyl group on the pyridone ring and diastereoselectivity was noted. Structures of the host–guest complexes were examined by 1H NMR and the data were used to obtain preliminary information concerning the mechanism of chiral induction within the confined spaces of OA capsule.
Gibb, C. L. D.; Gibb, B. C. Guests of Differing Polarities Provide Insight into Structural Requirements for Templates of Water-Soluble Nano-Capsules.. Tetrahedron 2009, 65, 7240-7248.
Publisher's Version

Guests covering a range of polarities were examined for their ability to bind to a water-soluble cavitand and trigger its assembly into a supramolecular capsule. Specifically the guests examined were: tridecane 2, 1-dodecanol 3, 2-nonyloxy ethanol (ethylene glycol monononyl ether) 4, 2-(2-hexyloxyethoxy) ethanol (Di(ethylene glycol) hexyl ether) 5, 2-[2-(2 propoxyethoxy)ethoxy] ethanol (Tri(ethylene glycol) propyl ether 6, and bis [2-(2-hydroxyethoxy)ethyl] ether (tetra(ethylene glycol)) 7. In this series, guest 6 proved to signify the boundary between assembly and the formation of 2:1 complexes, and simple 1:1 complexation. Thus, guests 2-5 formed relatively kinetically stable capsules, guest 6 formed a capsule that was unstable relative to the NMR timescale, and guest 7 formed a simple 1:1 complex.

Giles, M. D.; Liu, S.; Emanuel, R.; Gibb, B.; Grayson, S. Divergent Dendronization of Deep-Cavity Cavitands to Tune Host Solubility. Israel Journal of Chemistry 2009, 49, 31-40.
Publisher's Version
Abstract Resorcinarene-based deep-cavity cavitands (DCCs) are useful components in supramolecular chemistry because their extended cavity enables the encapsulation of relatively large guests. To provide H2O solubility, they have been modified with hydroxyl functionalized dendrons. This has been carried out by the divergent dendronization of aliphatic poly(ester) dendrons through the third dendritic generation. The resultant macromolecule demonstrated the desired H2O solubility.
Srinivasan, K.; Gibb, B. C. Synthesis of nanoscale carceplexes from deep-cavity cavitands. Chem. Commun. 2008, 4640-4642.
Publisher's Version
Deep-cavity cavitands were shown to undergo carceplex reactions in which two cavitand tetrols were covalently linked using bromochloromethane; the efficiency of the “dimerization” was closely tied to the templating guest molecule incarcerated within the host.
Srinivasan, K.; Laughrey, Z. R.; Gibb, B. C. Broad Functionalization of Deep-Cavity Cavitands by Directed ortho Metalation. European Journal of Organic Chemistry 2008, 2008, 3265-3271.
Publisher's Version
Abstract The endo- and exo-rim positions of deep-cavity cavitand 1 were functionalized by directed ortho metalation (DoM) procedures. A range of electrophilic quenchers led to hosts with ester, phenol and thioether functionality. In each case, a combination of host pre-organization and reaction control resulted in far fewer products than the theoretical sixty-nine. In addition to the nature of the lithiate, functionalization patterns were also dependent on the electrophile, with a general trend that the non-carbon electrophiles examined gave higher degrees of substitution. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Gibb, C.; Sundaresan, A. K.; Ramamurthy, V.; Gibb, B. C. Templation of the Excited-State Chemistry of α-(n-Alkyl) Dibenzyl Ketones:  How Guest Packing within a Nanoscale Supramolecular Capsule Influences Photochemistry. Journal of the American Chemical Society 2008, 130, 4069-4080.
Publisher's Version

Excited-state behavior of eight α-alkyl dibenzyl ketones (alkyl = CH3 through n-C8H17) that are capable of undergoing type II and/or type I photoreactions has been explored in isotropic solution and within a water-soluble capsule. The study consisted of two parts:  photochemistry that explored the excited-state chemistry and an NMR analysis that revealed the packing of each guest within the capsule. The NMR data (COSY, NOESY, and TOCSY experiments) revealed that ternary complexes between α-alkyl dibenzyl ketones and the capsule formed by two cavitands are kinetically stable, and the guests fall into three packing motifs modulated by the length of the α-alkyl chain. In essence, the host is acting as an external template to promote the formation of distinct guest conformers. The major products from all eight guests upon irradiation either in hexane or in buffer solution resulted from the well-known Norrish type I reaction. However, within the capsule the excited-state chemistry of the eight ketones was dependent on the alkyl chain length. The first group consisted of α-hexyl, α-heptyl, and α-octyl dibenzyl ketones that yielded large amounts of Norrish type II products within the host, while in solution the major products were from Norrish type I reaction. The second group consists of α-butyl and α-pentyl dibenzyl ketones that yield equimolar amounts of two rearranged starting ketones within the capsule (combined yield of ca 60\%), while in solution no such products were formed. The third group consisted of α-methyl, α-ethyl, and α-propyl dibenzyl ketones that within the capsule yielded only one (not two) rearranged starting ketone in larger amounts (21−35\%) while in solution no rearrangement product was obtained. Variation in the photochemistry of the guest within the capsule, with respect to the α-alkyl chain length of the guest, highlights the importance of how a small variation in supramolecular structure can influence the selectivity within a confined nanoscale reactor. 

Srinivasan, K.; Gibb, B. C. Electrophilic Substitution of Deep Cavity Cavitands:  Selective Exo Functionalization of Molecular Concavity. Organic Letters 2007, 9, 745-748.
Publisher's Version
The functionalization of deep-cavity cavitands via electrophilic substitution was investigated. In the parent structures, substitution occurs both at the exo position of the bowl-shaped hosts and on the convex face. Little or no endo substitution was observed. In contrast, derivatives in which methyl groups blocked the reaction sites on the convex face reacted selectively at the exo positions.
Kaanumalle, L. S.; Gibb, C. L. D.; Gibb, B. C.; Ramamurthy, V. Photo-Fries reaction in water made selective with a capsule. Org. Biomol. Chem. 2007, 5, 236-238.
Publisher's Version
The water soluble capsule formed by a deep cavity cavitand with eight carboxylic acid groups controls product distribution during photo-Fries rearrangement of naphthyl esters in water by restricting the mobility of primary singletradical pair.
Gibb, C. L. D.; Gibb, B. C. Templated Assembly of Water-Soluble Nano-Capsules:  Inter-Phase Sequestration, Storage, and Separation of Hydrocarbon Gases. Journal of the American Chemical Society 2006, 128, 16498-16499.
Publisher's Version
In aqueous solution, a deep-cavity cavitand was shown to self-assemble into dimeric nano-capsules via the sequestration of gaseous-phase hydrocarbons. The sequestration, assembly, and entrapment process was shown to be dependent on the hydrocarbon. Thus, by way of example, butane could be selectively sequestered from a propane−butane mixture.
Laughrey, Z. R.; Gibb, B. C. Directed Ortho Metallation of Deep Cavity Cavitands:  Functionalizing Molecular Concavity. The Journal of Organic Chemistry 2006, 71, 1289-1294.
Publisher's Version
Directed ortho metallation (DOM) processes have been used to functionalize the cavity and rim of title cavitand 1. The preorganization of the host resulted in a considerable reduction in the range of products produced. Thus, whereas sixty-nine products are possible from per-functionalization, only twelve were observed when the host was treated with three different alkyllithiums.
Kaanumalle, L. S.; Gibb, C. L. D.; Gibb, B. C.; Ramamurthy, V. A Hydrophobic Nanocapsule Controls the Photophysics of Aromatic Molecules by Suppressing Their Favored Solution Pathways. Journal of the American Chemical Society 2005, 127, 3674-3675.
Publisher's Version
A combination of hydrophobic forces and guest templation drive the assembly of cavitands into molecular capsules. Remarkably, anthracene that dimerizes with unit efficiency in solution does not dimerize within the capsule despite forming 2:2 complex. The capsule allows an unprecedented examination of the anthracene excimer.
Gong, J.; Gibb, B. C. A new macrocycle demonstrates ditopic recognition properties. Chem. Commun. 2005, 1393-1395.
Publisher's Version

The synthesis and binding properties of a new macrocycle is reported. The host, comprised of three basic pyridines, four hydrogen bond accepting carbonyls, and two hydrogen bond donating amide groups, binds mono-alkyl ammonium salts in a manner that is dependent on the counter-ion of the ammonium guest.

Kaanumalle, L. S.; Gibb, C. L. D.; Gibb, B. C.; Ramamurthy, V. Controlling Photochemistry with Distinct Hydrophobic Nanoenvironments. Journal of the American Chemical Society 2004, 126, 14366-14367.
Publisher's Version
A combination of hydrophobic forces and guest templation drive the assembly of cavitands into molecular capsules. Encapsulated guests such as dibenzyl ketones reside in an essentially dry environment, and upon irradiation, undergo rearrangement processes that are templated by the shape of the 1 nm × 2 nm cavity.
Gibb, C. L. D.; Gibb, B. C. Well-Defined, Organic Nanoenvironments in Water:  The Hydrophobic Effect Drives a Capsular Assembly. Journal of the American Chemical Society 2004, 126, 11408-11409.
Publisher's Version
The synthesis of a water-soluble, deep-cavity cavitand is reported. A blend of molecular curvature and amphiphilicity, this molecule has a hydrophobic concave surface and a hydrophilic convex surface. As a result, in aqueous solution and in the presence of a guest molecule, the host self-assembles to form a capsular assembly with an interior cavity large enough to entrap steroidal guests.