François P. Gabbaï

Fluoride Ion Complexation and Sensing Using Organoboron Compounds

Fluoride is often added to drinking water and toothpaste because of its beneficial effects in dental health. It is also administered in the treatment of osteoporosis.1 While the beneficial effects of fluoride are well documented, chronic exposure to high levels of this anion can lead to dental or even skeletal fluorosis.2-4 Taking into account these adverse effects, a great deal of attention has been devoted to the discovery of improved analytical methods for the detection of fluoride, especially in water. This field of research has also been stimulated by the potential use of such methods for the detection of phosphorofluoridate nerve agents such as Sarin or uranium hexafluoride, which release fluoride upon hydrolysis. In addition to these applications, the capture of fluoride, especially in water, is a stimulating academic challenge because of the high hydration enthalpy of this anion (∆H° ) -504 kJ mol-1). * To whom correspondence should be addressed. E-mail: simon.aldridge@ chem.ox.ac.uk (S.A.) and francois@tamu.edu (F.P.G.). † Texas A&M University. ‡ University of Oxford. Casey Wade was born in 1983 in Lynch, Nebraska. He earned a B.S. degree from the University of NebraskasLincoln in 2006. During his time there, he worked as an undergraduate researcher under the supervision of J. A. Belot and participated in a joint research internship at the American Air Liquide Chicago Research Center. In 2007, he joined the group of F. P. Gabbaı̈ at Texas A&M University, where he currently studies anion recognition using main group Lewis acids.

Fluoride Ion Recognition by Chelating and Cationic Boranes

Because of the ubiquity of fluoride ions and their potential toxicity at high doses, researchers would like to design receptors that selectively detect this anion. Fluoride is found in drinking water, toothpaste, and osteoporosis drugs. In addition, fluoride ions also can be detected as an indicator of uranium enrichment (via hydrolysis of UF(6)) or of the chemical warfare agent sarin, which releases the ion upon hydrolysis. However, because of its high hydration enthalpy, the fluoride anion is one of the most challenging targets for anion recognition. Among the various recognition strategies that are available, researchers have focused a great deal of attention on Lewis acidic boron compounds. These molecules typically interact with fluoride anions to form the corresponding fluoroborate species. In the case of simple triarylboranes, the fluoroborates are formed in organic solvents but not in water. To overcome this limitation, this Account examines various methods we have pursued to increase the fluoride-binding properties of boron-based receptors. We first considered the use of bifunctional boranes, which chelate the fluoride anion, such as 1,8-diborylnaphthalenes or heteronuclear 1-boryl-8-mercurio-naphthalenes. In these molecules, the neighboring Lewis acidic atoms can cooperatively interact with the anionic guest. Although the fluoride binding constants of the bifunctional compounds exceed those of neutral monofunctional boranes by several orders of magnitude, the incompatibility of these systems with aqueous media limits their utility. More recently, we have examined simple triarylboranes whose ligands are decorated by cationic ammonium or phosphonium groups. These cationic groups increase the electrophilic character of these boranes, and unlike their neutral analogs, they are able to complex fluoride in aqueous media. We have also considered cationic boranes, which form chelate complexes with fluoride anions. Our work demonstrates that Coulombic and chelate effects are additive and can be combined to boost the anion affinity of Lewis acidic hosts. The boron compounds that we have investigated present a set of photophysical and electrochemical properties that can serve to signal the fluoride-binding event. We can also apply this approach to cyanide complexation and are continuing our investigations in that area.

Cationic Boranes for the Complexation of Fluoride Ions in Water below the 4 ppm Maximum Contaminant Level

In search of a molecular receptor that could bind fluoride ions in water below the maximum contaminant level of 4 ppm set by the Environmental Protection Agency (EPA), we have investigated the water stability and fluoride binding properties of a series of phosphonium boranes of general formula [p-(Mes(2)B)C(6)H(4)(PPh(2)R)](+) with R = Me ([1](+)), Et ([2](+)), n-Pr ([3](+)), and Ph ([4](+)). These phosphonium boranes are water stable and react reversibly with water to form the corresponding zwitterionic hydroxide complexes of general formula p-(Mes(2)(HO)B)C(6)H(4)(PPh(2)R). They also react with fluoride ions to form the corresponding zwitterionic fluoride complexes of general formula p-(Mes(2)(F)B)C(6)H(4)(PPh(2)R). Spectrophotometric acid-base titrations carried out in H(2)O/MeOH (9:1 vol.) afford pK(R+) values of 7.3(+/-0.07) for [1](+), 6.92(+/-0.1) for [2](+), 6.59(+/-0.08) for [3](+), and 6.08(+/-0.09) for [4](+), thereby indicating that the Lewis acidity of the cationic boranes increases in following order: [1](+) < [2](+) < [3](+) < [4](+). In agreement with this observation, fluoride titration experiments in H(2)O/MeOH (9:1 vol.) show that the fluoride binding constants (K = 840(+/-50) M(-1) for [1](+), 2500(+/-200) M(-1) for [2](+), 4000(+/-300) M(-1) for [3](+), and 10 500(+/-1000) M(-1) for [4](+)) increase in the same order. These results show that the Lewis acidity of the cationic boranes increases with their hydrophobicity. The resulting Lewis acidity increase is substantial and exceeds 1 order of magnitude on going from [1](+) to [4](+). In turn, [4](+) is sufficiently fluorophilic to bind fluoride ions below the EPA contaminant level in pure water. These results indicate that phosphonium boranes related to [4](+) could be used as molecular recognition units in chemosensors for drinking water analysis.

Fluoride ion chelation by a bidentate phosphonium/borane Lewis acid.

The phosphonium borane [1-Mes2B-2-MePh2P-(C6H4)]+ ([2]+) has been synthesized as an iodide salt by alkylation of 1-Mes2B-2-Ph2P-(C6H4) with MeI. This novel cationic borane complexes fluoride to afford the corresponding zwitterionic fluoroborate complex 1-FMes2B-2-MePh2P-(C6H4) (2-F) with a binding constant in MeOH exceeding that of 1-Mes2B-4-MePh2P-(C6H4) ([1]+) by at least 4 orders of magnitude. Structural and computational results indicate that the high fluorophilicity of [2]+ arises from both Coulombic and cooperative effects which lead to formation of a B-F-->P interaction with a F-->P distance of 2.666(2) A. These results, which are supported by NBO and AIM analyses, show that the latent phosphorus-centered Lewis acidity of the phosphonium moiety in [2]+ can be exploited to enhance fluoride binding via chelation.

A bidentate borane as colorimetric fluoride ion sensor.

The bright yellow bidentate diborane (3), obtained by reaction of 10-bromo-9-thia-10-boraanthracene (1) with dimesityl-1,8-naphthalenediylborate (2), serves as a colorimetric anion sensor and selectively complexes fluoride with an association constant greater than 5 × 109 M−1 in THF.

Turn-On Fluorescence Sensing of Cyanide Ions in Aqueous Solution at Parts-per-Billion Concentrations

Cyanide is a highly toxic anion that has become a key component of many industrial processes. It is also produced naturally by a number of higher plants, which use it as a protection against predators. Release of this anion in the environment and an increase in the farming and consumption of cyanogenic plants such as cassava have served to spark a renewed interest in methods that can be used to sense the presence of this anion, especially in aqueous media. One of the current strategies adopted for the design of cyanide sensors is based on the use of electrophilic organic derivatives, which interact with the cyanide anion through formation of a new covalent bond. Although advantageous properties have been discovered, only a limited number of receptors function in water. f,m,7] Some of these receptors necessitate basic pH and high cyanide concentrations. Because of these limitations, strategies that rely on the use of Lewis acidic derivatives have been considered. Such derivatives include zinc–porphyrins, iron–hemes, corrins, and transition-metal complexes that interact with the cyanide anion through formation of a strong coordination bond. This approach, which is typically characterized by elevated binding constants, has been successfully applied to the detection of cyanide at the ppm level. Some of these receptors have also been shown to be compatible with biological matrices, making the detection of cyanide possible directly in plants. As demonstrated by a series of recent contributions, three-coordinate boranes possessing an accessible boron center can also be used as sensors for cyanide anions. Whereas neutral boranes can only be used in mostly organic environments, we and others have demonstrated that the incorporation of peripheral cationic groups in such compounds could be used to enhance their cyanide ion affinity. Although the cyanide affinity displayed by some of these boranes is very high, their practical use remains limited by the nature of the photophysical response observed during the recognition event. Indeed, cyanide coordination leads to population of the empty p orbital of boron, thus quenching the absorbance and fluorescence of the triarylboron chromophore. The turn-off rather than turn-on response observed in these complexes is not ideal from an analytical point of view and constitutes one of the major limitations affecting the practical use of cationic boranes as cyanide sensors. In order to overcome this limitation, we have now synthesized para-phenylene phosphonium borane/fluorophore conjugates, which behave as highly sensitive fluorescence turn-on sensors for the cyanide anion in aqueous solutions. Reaction of p-Ph2P-C6H4-BMes2 (Mes=mesityl) with 9bromomethyl anthracene in toluene, which was heated to reflux, afforded [1]Br in 82% yield (Scheme 1). A similar reaction involving p-Ph2P-C6H4-BMes2 and N-(3-bromo-

Sulfonium Boranes for the Selective Capture of Cyanide Ions in Water

Going fishing! The sulfonium borane [1](+) complexes cyanide in pure water at the maximum allowable concentration of 50 ppb recommended by the European Union. The high cyanide ion affinity displayed by this compound arises from favorable Coulombic effects augmented by a direct bonding interaction between the cyano and sulfonio groups.

A bidentate Lewis acid with a telluronium ion as an anion-binding site

The search for receptors that can selectively capture small and potentially toxic anions in protic media has sparked a renewed interest in the synthesis and anion-binding properties of polydentate Lewis acids. Seeking new paradigms to enhance the anion affinities of such systems, we synthesized a bidentate Lewis acid that contains a boryl and a telluronium moiety as Lewis acidic sites. Anion-complexation studies indicate that this telluronium borane displays a high affinity for fluoride in methanol. Structural and computational studies show that the unusual fluoride affinity of this bidentate telluronium borane can be correlated with the formation of a B-F → Te chelate motif supported by a strong lone-pair(F) → σ*(Te-C) donor-acceptor interaction. These results, which illustrate the viability of heavier chalcogenium centres as anion-binding sites, allow us to introduce a novel strategy for the design of polydentate Lewis acids with enhanced anion affinities.

Lewis acidity enhancement of triarylboranes via peripheral decoration with cationic groups.

The cationic boranes [Ar(N+)BMes(2)](+), [Ar(N+)(2)BMes](2+), and [Ar(N+)(3)B](3+) (Ar(N+) = [4-(Me(3)N)-2,6-Me(2)-C(6)H(2)](+); Mes = mesityl) have been synthesized and studied by cyclic voltammetry. The results obtained in this study show that the reduction potential of these derivatives in THF is increased by 0.36 V upon each substitution of a mesityl by a cationic Ar(N+) anilium group. Remarkably, the trication [3](3+), whose triflate salt is water soluble, complexes cyanide anions in pure water at pH 7. These properties underscore the dramatic effects caused by the increased number of cationic groups.

Sensing of Aqueous Fluoride Anions by Cationic Stibine–Palladium Complexes

Turn on the lantern! The stibine donor ligand of a cationic palladium complex acts as a Lewis acid and reacts with a fluoride anion to afford the corresponding fluorostiboranyl-palladium species (see scheme). Bindung of the fluoride anion to the antimony center induces a change in denticity of the triphosphine unit and leads to a bright-orange trigonal-bipyramidal d(8) lantern complex.