Fluorous Molecules Research Articles

Highly stable mixed halide perovskite quantum dots synthesized in the presence of fluorous ligands

AbstractThis work probes the potential of fluorous fatty acids as stabilizing ligands in the synthesis of mixed halide perovskite quantum dots (MHP QDs). Traditionally, MHP QDs are synthesized in the presence of oleic acid (OA) and oleyl amine (OAm). Here fluorous fatty acids have been used along with OA and OAm to yield MHP QDs with higher stability. Increased fractions of fluorous molecules in reaction mixture require the process to be carried out at a higher temperature due to the distinctive temperature‐dependent mixing behavior of perfluorinated ligands. Best of fluorous acid functionalized QDs in solution showed a 9% decrease in their photoluminescence quantum yield (PLQY) over 30 days compared to 27% in those without. The composition of fluorous fatty acids during synthesis influences the size, form and optical properties of MHP QDs. Further in situ addition of non‐carboxylic acid fluorous ligands (thiols) are also shown to the give similar improvements in stability and optical properties of MHP QDs. The in situ fluorous ligand functionalization studied in this work presents a new method to improve the stability of MHP‐QD while providing a thermally controlled handle to tune the structure of nanoparticle films.

Design and synthesis of fluorinated peptides for analysis of fluorous effects on the interconversion of polyproline helices

The unique interaction between fluorine atoms has been exploited to alter protein structures and to develop synthetic and analytical applications. To expand such fluorous interaction for novel applications, polyproline peptides represent an excellent molecular nanoscaffold for controlling the presentation of perfluoroalkyl groups on their unique secondary structure. We develop approaches to synthesis fluorinated peptides to systematically investigate how the number, location and types of the fluorous groups on polyproline affect the conformation by monitoring the transition between the two major polyproline structures PPI and PPII. This work provides valuable information on how fluorous interaction affects the peptide structure and also benefits the design of functional fluorous molecules.

Emergent Fluorous Molecules and Their Uses in Molecular Imaging.

This Account summarizes recent advances in the chemistry of fluorocarbon nanoemulsion (FC NE) functionalization. We describe new families of fluorous molecules, such as chelators, fluorophores, and peptides, that are soluble in FC oils. These materials have helped transform the field of in vivo molecular imaging by enabling sensitive and cell-specific imaging using magnetic resonance imaging (MRI), positron emission tomography (PET), and fluorescence detection. FC emulsions, historically considered for artificial blood substitutes, are routinely used for ultrasound imaging in clinic and have a proven safety profile and a well-characterized biodistribution and pharmacokinetics. The inertness of fluorocarbons contributes to their low toxicity but makes functionalization difficult. The high electronegativity of fluorine imparts very low cohesive energy density and Lewis basicity to heavily fluorinated compounds, making dissolution of metal ions and organic molecules challenging. Functionalization is further complicated by colloidal instability toward heat and pH, as well as limited availability of biocompatible surfactants.We have devised new fluorous chelators that overcome solubility barriers and are able to bind a range of metal ions with high thermodynamic stability and biocompatibility. NE harboring chelators in the fluorous phase are a powerful platform for the development of multimodal imaging agents. These compositions rapidly capture metal ions added to the aqueous phase, thereby functionalizing NEs in useful ways. For example, Fe3+ encapsulation imparts a strong paramagnetic relaxation effect on 19F T1 that dramatically accelerates 19F MRI data acquisition times and hence sensitivity in cell tracking applications. Alternatively, 89Zr encapsulation creates a sensitive and versatile PET probe for inflammatory macrophage detection. Adding lanthanides, such as Eu3+, renders NE luminescent. Beyond chelators, this Account further covers our progress in formulating NEs with fluorophores, such as cyanine or BODIPY dyes, with their utility demonstrated in fluorescence imaging, biosensing, flow cytometry and histology. Fluorous dyes soluble in FC oils are also key enablers for nascent whole-body imaging technologies such as cryo-fluorescence tomography (CFT). Additionally, fluorous cell-penetrating peptides inserted on the NE surface increase the uptake of NE by ∼8-fold in weakly phagocytic stem cells and lymphocytes used in immunotherapy, resulting in significant leaps in detection sensitivity in vivo.

Dissecting the packing forces in mixed perfluorocarbon/aromatic co-crystals

The nature and role of non-covalent interactions involving fluorous molecules and aromatic molecules are studied by a combined theoretical/crystallographic approach.

Fluorous molecules for dye-sensitized solar cells: synthesis and properties of di-branched, di-anchoring organic sensitizers containing fluorene subunits

Four organic sensitizers having a di-branched molecular structure D–(π–A)2 were applied in the development of dye-sensitized solar cells (DSSCs).

ChemInform Abstract: Highly Selective Perfluoroalkylation of Unsaturated Molecules Upon Photoirradiation in BTF as an Organic/Fluorous Hybrid Solvent

AbstractReview: 74 refs.

Highly Selective Perfluoroalkylation of Unsaturated Molecules upon Photoirradiation in BTF as an Organic/Fluorous Hybrid Solvent

Benzotrifluoride (BTF), an eco-friendly solvent, can dissolve many organic and fluorous molecules because of the organic and fluorous motifs in its structure. Using BTF as solvent, we have developed a series of reactions for perfluoroalkylation of various unsaturated compounds upon photoirradiation with a Xe lamp through Pyrex. For example, alkynes, allenes, vinylcyclopropanes, isocyanides, diynes, dienes, and enynes successfully undergo regioselective perfluoroalkyliodination, perfluoroalkylselenation, and perfluoroalkyltelluration in BTF. In addition, the present photoinitiation procedure can be applied to trifluoromethylation

Rhodamine F: a novel class of fluorous ponytailed dyes for bioconjugation

Incorporation of fluorous ponytails such as polyfluorinated alkyl residues (CH2)m(CF2)nCF3 leads to a novel class of bright rhodamine-based fluorescence dyes. These dyes combine the excellent photophysical properties of the frequently used rhodamine dyes with the unique features of "light" fluorous molecules. One of those features is the possibility to separate substances utilizing fluorous solid-phase extraction (F-SPE), which is based on the specific intermolecular interaction between fluorous compounds. Thus, molecules, which are labeled with these new dyes, are not only accessible to fluorescence experiments, but can also be easily purified (via so-called FluoroFlash columns) prior to use. The dyes were bound to a cell penetrating peptoid (polycationic oligo(N-substituted) glycine) on solid supports. These conjugates were purified with F-SPE before their photophysical and biological properties were investigated.

Fluorous Molecules for Dye-Sensitized Solar Cells: Synthesis and Characterization of Fluorene-Bridged Donor/Acceptor Dyes with Bulky Perfluoroalkoxy Substituents

A series of structurally related sensitizers containing fluorene as a π-conjugated central core have been synthesized, characterized, and applied in the development of dye-sensitized solar cells (DSSCs). The new electron donor (diphenylamine)–acceptor (cyanoacrylic acid) D-π-A molecular structures hold perfluoro-tert-butyl substituents in different positions. It is demonstrated that the fluorous substitution pattern remarkably affects the behavior of dyes as photosensitizers in DSSCs, leading to an improvement in the power conversion efficiencies with respect to analogous nonfluorous molecules.

ChemInform Abstract: Structural, Physical, and Chemical Properties of Fluorous Compounds

AbstractReview: 87 refs.

Fluorous Molecules for Dye-Sensitized Solar Cells: Synthesis and Photoelectrochemistry of Unsymmetrical Zinc Phthalocyanine Sensitizers with Bulky Fluorophilic Donor Groups

Two sterically hindered zinc phthalocyanines bearing fluorous alkoxy substituents and carboxylic acid groups acting respectively as electron donor and electron acceptor/anchoring units, were synthesized and their ability to photosensitize nanocrystalline TiO2 films was investigated. The electronic properties of these new dyes were characterized by combining UV−vis spectroscopy, electrochemical techniques and DFT computation. Nanocrystalline TiO2 electrodes treated with the fluorous dyes were assembled in dye-sensitized solar cells (DSCs) and further characterized by photocurrent action spectroscopy, photocurrent-photovoltage measurements and electrochemical impedance spectroscopy. The maximum photon-to-current conversion efficiencies (IPCE) in the near IR region compared favorably with those achieved with some of the best phthalocyanine dyes investigated so far, thus highlighting the potential of fluorous molecules as DSC components. A maximum power conversion efficiency (η) of 1.3% was attained in the ab...

Themed series in organo-fluorine chemistry

It is a great pleasure to be able to introduce this Themed series on organo-fluorine chemistry in the Beilstein Journal of Organic Chemistry. The introduction of fluorine into organic molecules is widely practiced particularly when tuning the properties of molecules for specialist functions. Of particular prominence is the role fluorine substitution finds in pharmaceutical development [1], and selective fluorination has made a major contribution to the bioactivity of a wide range of agrochemical products [2]. Organo-fluorine compounds have also found a significant role in soft materials chemistry such as liquid crystals, photoresist polymers and self assembling monolayers [3]. Allied to this breadth of activity is a steady development in the number and range of fluorination reagents and methodologies. DAST/Deoxofluor, HF:amine reagents and TBAF have secured a central role in the armory of organic chemists and the ready availability and improvements in their formulations are allowing these reagents to be incorporated beyond the research lab and into process development. Indeed micro-reactor technology is enabling elemental fluorine to be used in large scale organo-fluorine production [4]. The introduction in the early 1990's of air stable electrophilic fluorinating reagents such as Selectfluor [5] has been revolutionary and has opened up many new methods for fluorine introduction, and provided the foundation for intense research efforts into asymmetric fluorinations leading now to some exquisite catalytic asymmetric methodologies [6]. The changes in behaviour of a molecule after the introduction of a fluorine atom continue to be unpredictable, and understanding such behaviour remains a driver in organo-fluorine research [7]. Investigations into the stereoelectronic influence of fluorine and the nature of weak interactions between fluorine and other substituents remains an active area of research and for example important insights into how fluorinated drugs interact with proteins are emerging as a result of accumulating crystallographic data of protein-drug interactions [8]. Exploring the role and nature of fluorous molecules has been an intense area of research internationally [9], one which has had a relatively short lead time since the seminal paper of Horvath and Rabai in 1994 [10]. In the area of medical imaging, positron emission tomography (PET) has undergone a step change in growth across all developing countries, with an exponential increase in the installation of PET cameras and cyclotrons to generate isotope for labelling ligands and diagnostic probes. 18F is an important isotope in PET because it has a relatively long half life (t1/2 = 110 min) and methods for introducing fluorine, appropriate to PET synthesis are in demand and will continue to grow. So the field is active and exciting and it is in that context that the BJOC feels it appropriate to profile a themed series in the area. Contributions to the series come from an international grouping of noted experts in fluorine chemistry and we are delighted that they have agreed to contribute their papers for such a successful launch.

ライトフルオラスタグを基点とする有機反応プロセスの簡略化

Organic molecules bearing small fluorous tags (C6F13, C8F17) are called light fluorous molecules. Light fluorous reagents, scavengers and catalysts are especially convenient since they typically induce reactions of organic substrates under the same conditions as their non-fluorous relatives, but are reliably removed from crude reaction products by fluorous solid phase extraction. Herein we report light fluorous versions of Grubbs-Hoveyda metathesis catalysts, Mukaiyama reagent, and Fmoc reagent. These exhibit the expected reactivity profile, are readily recovered from reaction mixtures by fluorous solid phase extraction. In addition, we describe reverse-fluorous solid phase extraction. In a reversal of the roles of solid and liquid phases in standard fluorous solid phase extraction, a mixture is charged to a polar solid phase (standard silica gel) and then eluted with a fluorous solvent. The organic components of the mixture are retained, while the fluorous components pass.

Fluorous Tagging Strategy for Solution‐Phase Synthesis of Small Molecules, Peptides and Oligosaccharides

AbstractFor Abstract see ChemInform Abstract in Full Text.

Increasing Fluorous Partition Coefficients by Solvent Tuning

Low partition coefficients of fluorous components have been a persistent problem in liquid-liquid separations using perfluoroalkanes as the fluorous phase. Solvent tuning of both the nonfluorous and the fluorous phase dramatically enhances the partitioning of light or polar fluorous molecules into the fluorous liquid phase, while minimally effecting partition coefficients of nonfluorous molecules. These findings suggest an expanded scope for liquid-based separations in fluorous biphasic catalysis, fluorous-tagged reagents, fluorous-supported oligomer synthesis, and related areas. [reaction: see text]

Prediction of Partition Coefficients of Fluorous and Nonfluorous Solutes in Fluorous Biphasic Solvent Systems by Mobile Order and Disorder Theory

The universal model for predicting lipophilicity based on the mobile order and disorder (MOD) solution thermodynamics was used for the successful prediction of the partition coefficient of 88 fluorous and nonfluorous chemicals in fluorous biphasic PFMCH/toluene and FC-72/benzene binary solvent systems at 25 °C. A general thermodynamic expression aimed to calculate the distribution of substances in any fluorous biphasic system at any temperature is presented. Interestingly, the predictive expression requires the knowledge of only the molar volume and the nonspecific cohesion parameter of the solute allowing valuable estimation of log P of nonexisting fluorous molecules. The present partition model predicts that grafting more and/or longer perfluoroalkyl tails on a given substance does not automatically result in higher partition coefficients.

A green protocol for the silylation of alcohols using bonded fluorous phase catalysisThis work was presented at the Green Solvents for Catalysis Meeting, held in Bruchsal, Germany, 13–16th October 2002.

The surface of a solid silica support has been functionalized with long perfluoroalkyl chains. The resulting surface layer readily adsorbs fluorous molecules from organic solutions. In this way, dirhodium(II) perfluorocarboxylate catalysts can be conveniently immobilized on a solid support. The resulting Bonded Fluorous Phase (BFP) catalysts display a high activity in the silane alcoholysis reaction using a solventless procedure and are easily recycled.

An improved design of fluorophilic molecules: prediction of the ln P fluorous partition coefficient, fluorophilicity, using 3D QSAR descriptors and neural networks

A combination of 3D QSAR molecular descriptors and artificial neural networks have been used to predict fluorophilicities, the natural logarithm of the perfluoro(methylcyclohexane)/toluene partition coefficients, for a wide range of partially fluorinated organic compounds. The average error of the predictions was less than twice the 0.2 experimental error. Multiple linear regression proved to be much less efficient. To better characterise the fluorous partition phenomenon, specific fluorophilicity was defined as the product of fluorophilicity and of the ratio of the van der Waals volumes of the expelled fluorous solvent and the entering solute molecules. This dimensionless term correlates well in a compound family with the calculated Hildebrand parameters of the fluorous molecules. The trifluoromethyl group was found highly effective for increasing the fluorous phase affinities of model compounds when used in combination with longer perfluoroalkyl groups.

Supramolecular potentials and embraces for fluorous aromatic molecules

In order to understand better the supramolecular chemistry of fluorous molecules, and particularly coordination complexes and organometallic molecules with perfluoroaromatic substituents, the relevant intermolecular potentials have been parametrised. It is shown that density functional calculations using the Perdew–Wang PWC functional and numerical basis sets adequately describe weak intermolecular attractive energies [e.g. (C6H6)2], but that gradient corrected BP or BLYP functionals do not. Due to a dearth of experimental data on intermolecular energies for perfluoroaromatic systems, these density functional calculations of the supramolecular isomers of (C6F6)2 are used to parametrise the Lennard-Jones plus electrostatic potential for fluoroaromatic and derivative molecules. Intermolecular energies for local interactions in the crystal structures of C6F6, C6F6·C6D6, and octafluoronaphthalene are reported. Strong directionality is not observed in the supramolecular forces between fluoroaromatics and the electrostatic components of the intermolecular energies are small, <15% of the total; the polarisation of the C–F bond is also less than expected from electronegativity differences. Perfluorinated molecules and ions such as [B(C6F5)4]− engage in multiple phenyl embrace motifs, comparable to those of phenylated molecules, despite the reversed polarity of aromatic C–F relative to C–H bonds (and the opposite quadrupole moments of C6F6 and C6H6). Examples of the sixfold perfluorophenyl embrace (6PFE), the hexagonal array of sixfold perfluorophenyl embraces (HA6PFE), and fourfold perfluorophenyl embraces (4PFE) are described. The intermolecular attractive energies of some of these motifs comprised of concerted edge-to-face and offset-face-to-face interactions are in the range −5.5 to −11.7 kcal mol−1. It is concluded that there are no major differences between the supramolecular motifs and energies of perfluorinated- and hydroaromatics.

Fluorous synthesis: a fluorous-phase strategy for improving separation efficiency in organic synthesis.

Recovery and purification difficulties can limit the yield and utility of otherwise successful organic synthesis strategies. A "fluorous synthesis" approach is outlined in which organic molecules are rendered soluble in fluorocarbon solvents by attachment of a suitable fluorocarbon group. Fluorocarbon solvents are usually immiscible in organic solutions, and fluorous molecules partition out of an organic phase and into a fluorous phase in a standard liquid-liquid extraction. Simple yet substantive separations of organic reaction mixtures are achieved without resorting to chromatography. Because fluorous synthesis combines in many respects the favorable purification features of solid-phase synthesis with the favorable reaction, identification, and analysis features of traditional organic synthesis, it should prove valuable in the automated synthesis of libraries of individual pure organic compounds.