Christopher G. Clark

Phase separation and affinity between a fluorinated perylene diimide dye and an alkyl-substituted hexa-peri-hexabenzocoronene

Fluorination of alkyl groups is a known strategy for hindering miscibility, thus promoting phase separation, when blends are prepared with a hydrocarbon compound. A new perylene bis(dicarboximide) derivative functionalized with branched N-perfluoroalkyl moieties (BPF-PDI) has been synthesized as electron acceptor to be potentially used in conjunction with the electron donor hexakis(dodecyl)hexabenzocoronene (HBC-C12) in bulk heterojunction solar cells. Aiming at controlling self-assembly between the two components at the supramolecular level, stoichiometric blends in CHCl3 have been prepared either by spin- or drop-casting onto silicon surfaces, and further subjected to solvent vapour annealing (SVA) treatment in a CHCl3-saturated atmosphere. Spectroscopic investigation in solution shows the formation of supramolecular BPF-PDI–HBC-C12 dimers, with an association constant Kass = (2.1 ± 0.3) × 104 M−1, pointing to a strong and unexpected affinity between the two species within the mixture. Characterization through optical and atomic force microscopies of the deposited samples revealed that the self-assembly behaviour of the blends on SiOx is remarkably different from mono-component films, thus confirming the absence of a macroscopic phase-separation between the two components featuring isolated domains of the neat acceptor or donor compound. In addition, X-ray studies provided evidence for the existence of a local-scale phase separation. These findings are of importance for organic photovoltaics, since they offer a new strategy to control the phase separation at different scales in electron acceptor–donor blends.

Molecularly tethered amphiphiles as 3-D supramolecular assembly platforms: unlocking a trapped conformation.

A fluorous biphasic hexa(3,5-substituted-phenyl)benzene (HPB), analogous to semifluorinated alkanes, was synthesized such that precise chemical and orthogonally directed, supramolecular placement of amphiphilic side chains at their bulk density was achieved. The grafting or tethering of incommensurate hydrocarbon and fluorocarbon chains to the rotationally flexible HPB core inextricably links intermolecular phase separation with intramolecular conformational behavior and results in rich self-assembly. The self-assembled structure was studied with polarized optical microscopy, differential scanning calorimetry, X-ray scattering, and (19)F magic-angle spinning solid-state NMR and found to be kinetically trapped with mixed fluorocarbon and hydrocarbon side chains, despite packing into a lattice defined by the HPB scaffold. The addition of 1% of the parent biphasic diphenylacetylene unlocks the frustrated conformation in the HPB, resulting in the formation of a thermodynamically favorable bilayer structure.

Tris(2,2′‐bipyridyl)ruthenium(II) with Branched Polyphenylene Shells: A Family of Charged Shape‐Persistent Nanoparticles

Polyphenylene dendrimers with poly(pentaphenylbenzene) branches (PPDs) are special within dendrimer chemistry because of their stiff, mostly radial arms that do not allow backfolding, thus rendering the molecules shapepersistent. As a result, their overall shapes are defined by the geometry of the particular core unit, and different cores (Figure 1a–c) have been proven to generate structural diversity. The highest core symmetry that approaches spherical PPDs has, however, been limited to a four-armed, tetrahedral tetraphenylmethane core (Figure 1c), since higher symmetries, such as octahedral, are challenging to achieve in organic chemistry. A powerful tool for building structures with controlled symmetry is instead provided by the use of organometallic complexes as core units such as the wellknown tris(2,2’-bipyridyl)ruthenium(II) complex ({Ru(bpy)3}, Figure 1d). This complex has already been employed as a functional core in a variety of non-shape-persistent dendrimers, mainly for investigating the effect that site isolation has on the properties of the ruthenium-based chromophore (for example, excited-state lifetimes) or for the design of light-harvesting systems. Moreover, it possesses an almost perfect octahedral coordination geometry and is shapepersistent itself, and thus can serve as the desired PPD core when dendritic wedges are attached to the six positions para to its nitrogen atoms (Figure 1d). In addition, the {Ru(bpy)3} core provides valuable synthetic handles: First, it introduces two positive charges within the center of the stiff and nonpolar PPD backbone, thus giving the dendrimer the character of a large, weakly coordinating dication. Second, this core is constructed by metal complexation, which is expected to deliver a facile and versatile tool for the synthesis of desymmetrized PPDs if the ligand (dendron) attachment is performed stepwise. The reaction sequence established for the synthesis of high-generation, monodisperse polyphenylene dendrimers is based on a [4+2] Diels–Alder cycloaddition of a triisopropylsilyl (TIPS) protected ethynyl-substituted cyclopentadienone branching unit to an ethynyl-substituted core or dendrimer, followed by removal of the TIPS groups, which activates the molecule for further growth. Since 2,2’bipyridine has no known reactivity under Diels–Alder conditions, it offers the opportunity to either grow the dendrimer divergently or to synthesize the polyphenylene dendrons first and then build the dendrimer by metal complexation in the final step (“convergent” approach). The key component in the two synthetic strategies for {Ru(bpy)3}-cored PPDs is 4,4’-bis(ethynyl)-2,2’-bipyridine (1). The reported synthesis of 1 consists of six steps and is complicated by weakly soluble 2,2’-bipyridine (bpy) intermediates. Therefore, a new five-step synthesis was develFigure 1. PPD cores (the arrows indicate the positions for dendrimer growth): a) biphenyl, b) hexaphenylbenzene, c) tetraphenylmethane (Td), and d) {Ru(bpy)3}.

Thermodynamic, structural, and nanomechanical properties of a fluorous biphasic material

The dynamics of the amphiphilic semifluorinated F(CF2)12(CH2)12H (F12H12) alkane that undergoes two condensed phase transitions have been investigated by Brillouin light spectroscopy, shear rheometry, small- (SAXS) and wide-angle (WAXS) X-ray scattering, and thermodynamic PVT measurements. The solid (I)-solid (II) transition (Ts) is marked by a stronger temperature dependence of the sound velocity in phase II and by a 2 orders of magnitude drop of the shear modulus. Between the Ts and the melting transition (Tm), the presence of two phonons implies a coexistence of solid (II) and amorphous (liquid) regions in the submicrometer range at thermal equilibrium as revealed by the SAXS pattern of a single reflection superimposed on a very broad amorphous halo. This intriguing finding of a transient, very slow (over 10 h) solid/liquid coexistence within phase II is rationalized by a two-stage mechanism for melting of the smectic phase (II) of F12H12. A refinement of the known packing motifs for the two solid-state structures is proposed.

Solid-state organization of semifluorinated alkanes probed by 19F MAS NMR spectroscopy.

Bulk-phase self-assembly of a series of semifluorinated alkanes (SFAs) with hydrocarbon chains of varying length has been investigated by 19F NMR spectroscopy. At room temperature, a single 19F resonance for the terminal sCF3 group was observed at -81.7 ppm for perfluorododecylhexane (F12H6), whereas a sCF3 resonance was seen at -82.5 ppm for perfluorododecyldodecane (F12H12) and perfluorododecyleicosane (F12H20). This difference in chemical shift position is ascribed to the different molecular packing geometries, i.e., a monolayer lamellar structure for F12H6 vs a bilayer lamellar organization for F12H12 and F12H20. Moreover, in F12H12, a solid-solid phase transition from bilayer to monolayer lamellae can be followed by 19F NMR spectroscopy. 1H/19F-->13C CPMAS experiments indicated that the phase transition is accompanied by disordering of hydrocarbon chains, but does not involve a significant conformational change in the fluorocarbon chains. Yet, a change in the 19F T1 relaxation times was found to occur at the phase transition temperature, suggesting a change in the packing environments of the fluorocarbon chains. Two-dimensional exchange NMR experiments yielded cross-peaks between terminal sCF3 and inner sCF2CH2s moieties for the high-temperature monolayer phase, providing clear evidence for the spatial proximity between these groups. On the basis of these findings, we propose a model for the phase transition involving bilayer lamellae and monolayer lamellae with hydrocarbon and fluorocarbon interdigitation.

Dynamics and Kinetics of Structure Formation in Molecularly Tethered Fluorocarbon/Hydrocarbon Amphiphiles

Biphasic fluorocarbon/hydrocarbon amphiphiles tethered to cores at distances commensurate with their packing requirement can provide thermodynamic pathways toward equilibrium. This contrasts with the analogous semifluorinated alkanes. The dynamics of a fluorous biphasic hexa(3,5-substituted-phenyl)benzene (HPB) is studied with dielectric spectroscopy as a function of temperature and pressure in comparison to the parent biphasic diphenylacetylene (DPA). Dielectric spectroscopy is a sensitive probe of the fluorocarbon environment through the end C-F dipole. Four dielectrically active processes were observed that associate with the CF(3) environment within the different phases (isotropic, liquid-like lamellar, solid lamellar, glassy state). Pressure facilitates the construction of the equilibrium phase diagram. The kinetic pathways to fluorocarbon organization are explored by pressure-jump experiments. A highly cooperative process was found that is atypical of a nucleation and growth process expected for first-order transitions.

Viscoelasticity of semifluorinated alkanes at the air/water interface

As semifluorinated alkanes (SFA) present an unusual class of mesogenic units for supramolecular structure formation, the study of their physical properties and self-assembly at fluid interfaces is of substantial relevance. To this end, the two-dimensional phase behavior and the viscoelastic properties of semifluorinated alkanes with symmetric number of carbon atoms in the fluorinated and hydrogenated side chains (F(CF2)12–(CH2)12H and F(CF2)11CH2–core–(CH2)12H with dibromophenyl core were investigated at the air/water interface and compared to the asymmetric F(CF2)12(CH2)20H system. Surface pressure/area isotherms and compression–expansion cycles were recorded at 20 °C, 40 °C, and 50 °C. Depending on the molecular details, an unexpected phase transition and hysteresis in compression–expansion cycles could be observed. Interfacial rheology revealed for all monolayer systems a solid-like viscoelastic response over the investigated range of surface pressures. The interfacial storage modulus G′i and interfacial loss modulus G′′i increased with increasing surface pressure. More importantly, at constant surface pressure the simple semifluorinated alkanes, forming nearly circular 2D micellar structures at the interface, exhibited rheological properties reminiscent of glass-like colloid systems. On the other hand, the SFA with the dibromophenyl core formed 2D interfacial micelles of highly elongated shape with dendritic domains and exhibited gel-like rheological properties, similar to those of the asymmetric alkane. Moreover, with increasing surface pressure the response of the asymmetric system alters from glassy to gel-like. These findings suggest that fine differences in the molecular structure are reflected in the linear viscoelastic response of the Langmuir films, and hence offer the possibility to molecularly tune the rheology of fluid interfaces.

Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: Results from the ETOP Lungscape Project

Background Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods Clinically annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is >1% for most of the ∼150 (13 genes) mutations covered in the multiplex test. Results Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63 µg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases. Conclusion Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I-III NSCLC cohort, none of the mutations characterized showed prognostic significance.

Viscoelasticity of Semifluorinated Alkanes at the Air—Water Interface

We have studied the viscoelastic properties of semifluorinated alkanes F(CF2)n(CH2)mH (referred as FnHm) confined at the air‐water interface. These specially synthesized model doubly‐hydrophobic macromolecules of varying architecture reside at the air‐water interface in the form of well‐defined disk‐like surface micelles that minimize the free energy. Pressure area isotherms performed on Langmuir monolayers of these micelles indicated two transitions: one at about 4 mN/m and a second at about 8 mN/m. In both regimes a solid‐like viscoelastic response was probed. In each regime the values of both the storage and the loss surface moduli increased with surface pressure. These findings are discussed in view of recent theoretical developments and provide opportunities for manipulating surface structure and rheology of such types of complex macromolecules. Finally, the effect of architecture on this surface structure—rheology interplay has been also addressed.