Lukáš Severa

Helquats: A Facile, Modular, Scalable Route to Novel Helical Dications

The synthesis and properties of helical extended diquat (helquat), and derivatives that bear resemblance to diquat and azoniahelicene, was reported. Triyne with elongated tethers connecting the heterocyclic moiety with the pendant alkyne functionalities undergoing cycloisomerization give helquat featuring two seven-membered rings. The seven helquats reported are accessed uniformly in three steps from commercially available starting materials, entailing a Sonogashira coupling, bisquaternization, cycloisomerization, and 2+2+2 cycloisomerization. The evidence for the reversible electrochemical Weiz-type manifold and regular columnar stacks in crystal structures suggest the potential of helquats as electroactive functional elements.

Chiral analysis of helquats by capillary electrophoresis: resolution of helical N-heteroaromatic dications using randomly sulfated cyclodextrins.

Enantiomers of helical N‐heteroaromatic dications, helquats, were separated by CE. An acidic 22/35 mM sodium/phosphate background electrolyte, pH 2.4, with addition of randomly sulfated α‐, β‐ and γ‐ cyclodextrins allowed enantioresolution of a series of helquats, which comprised 5, 6 and 7 fused rings participating in the helical backbone. In general, at least one of the chiral selectors was found to provide baseline separation for 22 out of 24 helquats and partial separation for the remaining two. Individually, the sulfated γ‐cyclodextrin turned out to separate 79% of the helquats, followed by the β‐ and α‐congeners with 54 and 42% of the resolved compounds, respectively. Migration order of enantiomers was inspected for selected helquats and a relation of molecular size of the analytes to a cavity of the cyclodextrin selectors is discussed.

Resolution of a configurationally stable [5]helquat: enantiocomposition analysis of a helicene congener by capillary electrophoresis

Racemic [5]helquat as a triflate salt has been synthesized using a robust, three-step procedure. Subsequent exchange of triflate anions for inexpensive (R,R)-dibenzoyltartrate anions via an ion exchange resin afforded two diastereoisomeric salts. Crystallization led to the resolution of the helquat (ee > 98%). This is the first time that a non-racemic helquat has been obtained; its helicity having been assigned and its racemization barrier determined. Capillary electrophoresis with a sulfated β-cyclodextrin chiral selector is introduced for the first time as a straightforward method to analyze the enantiocomposition of charged, helicene-like species.

[6]Saddlequat: a [6]helquat captured on its racemization pathway

A dicationic [6]helicene congener captured on the racemization pathway in its saddle-shaped geometry is introduced. Synthesis, structure, resolution, and dynamic properties of this chiral [6]saddlequat in-between and its highly stereocontrolled transformation into enantiopure [6]helquat are discussed and demonstrated. The dynamic aspects established by experiment and supported by detailed DFT-D calculations are presented visually in the form of a movie (electronic table-of-contents and electronic supplementary information). The title [6]saddlequat was found to be an isolable chiral species on the entirely chiral enantiomerization pathway of a [6]helquat that is discussed as an example of Mislows “rubber glove” molecule.

Helquat-Induced Chiroselective Aggregation of Au NPs

Au nanoparticles (NPs) are functionalized with chiral (R) or (S) binaphthol phenylboronic acid ligands, (1a) or (1b). The (R)- or (S)-binaphthol phenylboronic acid ligands form donor-acceptor complexes with the chiral dicationic helicene, helquat (P)-HQ(2+) or (M)-HQ(2+), (2a) or (2b). The association constants between (1a)/(2a) and (1a)/(2b) correspond to (7.0 ± 0.5) × 10(5) M(-1) and (2.5 ± 0.3) × 10(5) M(-1), respectively, whereas the association constants between (1b)/(2b) and (1b)/(2a) correspond to (4.0 ± 0.5) × 10(5) M(-1) and (1.8 ± 0.3) × 10(5) M(-1), respectively. Chiroselective aggregation of chiral binaphthol phenylboronic acid-capped Au NPs triggered by the chiral helquats, is demonstrated.

Can Hindered Intramolecular Vibrational Energy Redistribution Lead to Non-Ergodic Behavior of Medium-Sized Ion Pairs?†

Ergodicity, that is, the ability to predict the behavior of an ensemble from the behavior of its components, is a key concept in various areas of science, while in daily life nonergodic behavior is quite common. In chemistry, ergodicity is typically associated with energy partitioning at a molecular level. Given the selective excitation of a certain rovibrational mode, for example, it is generally assumed that intramolecular vibrational energy redistribution (IVR) is much faster than interactions with the environment. Chemical systems are hence generally assumed to behave ergodically, that is, their properties and in particular their reactivities do not depend on the way of activation, but only on the total energy content, irrespective of the initial state. In turn, nonergodic behavior refers to chemical systems in which the outcome of a reaction is determined by the initial conditions. Most known examples for non-ergodic behavior in chemistry involve systems containing very few atoms, and even systems only slightly larger (e.g. ionized acetone) typically behave ergodically. In recent years, however, electron-capture induced dissociation (ECID) of biomolecules, that is, the recombination of an electron with a multiply charged cation, has been proposed to involve highly excited states of the charged-reduced species, whose dissociations are fast and may not follow ergodicity. Similar arguments have been put forward for highly exothermic electron-transfer reactions between dications and neutral molecules or rapid dissociation/abstraction reactions. However, for thermal reactions of medium-sized molecules, not only associated with the cleavage of existing, but also with the formation of new chemical bonds, many chemists (including ourselves) would generally deny a non-ergodic behavior. In the context of possible correlations between gaseous ions and condensed-phase properties, we recently identified a case which challenges the general assumption of ergodic behavior. Specifically, we investigated the noncovalent ion pairs of a triflate ion (TfO =CF3SO3 ) with a bispyridinium ion that exists in two separable conformers (see structures in Figure 1), which have been termed as helquat (h-1) and saddlequat (s-1), respectively. Amongst a series of other mass spectrometric studies, we have recorded the infrared-multiphoton dissociation (IRMPD) spectra of the mass-selected ion pairs [h1·TfO ] and [s-1·TfO ] . The exclusive fragmentation in IRMPD is a loss of triflic acid through a kinetically controlled Hofmann elimination and is thus associated with the formation of an O H bond. Surprisingly, the IRMPD spectra do not agree with either the experimental IR spectra of the solid salts [h-1·2TfO ] and [s-1·2TfO ], respectively, or the computed IR spectra of the singly charged, binary ion pairs [h-1·TfO ] and [s-1·TfO ] (Figure 1). Favorable agreement is obtained, however, if only the S=O stretching modes (scaling factor 1.0325) are allowed to be active in IRMPD. In this respect it is important to realize that IRMPD is an action spectroscopy, in which the infrared absorption of a gaseous ion is monitored through the amount of fragmentation induced. While this may lead to significant discrimination of certain modes, a situation as profound as in Figure 1, that is, the practical absence of all modes other than certain heteronuclear stretches, has not been addressed before. One possible explanation for the exclusive response of the S=O modes to the infrared irradiation in the IRMPD experiments is a non-ergodic behavior of the ion pairs [h1·TfO ] and [s-1·TfO ]. Thus, the hypothesis is that the S= O bands experience limited intramolecular vibrational energy redistribution (IVR) with the other modes of the molecule such that the triflate unit “overheats”, until proton abstraction becomes kinetically feasible. In turn, adsorption of IR photons in the organic backbone is associated with rapid IVR and hence dissipation of the excess energy across the molecule. While the argument involving non-ergodicity appears fascinating, a problem is that—much like with other [*] Dr. C. J. Shaffer, Dr. . R v sz, Dr. D. Schrcder, Ing. L. Severa, Dr. F. Teplý Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Flemingovo n m. 2, 16610 Prague 6 (Czech Republic) E-mail: schroeder@uochb.cas.cz

Search for conglomerate in set of [7]helquat salts: multigram resolution of helicene-viologen hybrid by preferential crystallization.

Investigation of a set of 12 [7]helquat salts by X-ray crystal diffraction led to identification of conglomerate behavior in bis(trifluoroacetate) salt [2][CF(3)CO(2)](2). This is to demonstrate that a systematic search for conglomerates can be performed for a given helicenoid enabling straightforward multigram resolution via preferential crystallization. Subsequently, preferential crystallization of this chiral helicene-viologen hybrid has been established to obtain pure P and M enantiomers on a multigram scale, 5 g each. Furthermore, preparation of nonracemic samples of [7]helquat 2 via diastereomeric (R,R)-dibenzoyltartrate salts is described, and determination of absolute configuration and racemization barrier is also reported.

Tunable Chiral Second-Order Nonlinear Optical Chromophores Based on Helquat Dications

Fourteen new dipolar cations have been synthesized, containing methoxy or tertiary amino electron donor groups attached to helquat (Hq) acceptors. These Hq derivatives have been characterized as their TfO- salts by using various techniques including NMR and electronic absorption spectroscopies. UV-vis spectra show intense, relatively low energy absorptions with λmax ≈ 400-600 nm, attributable to intramolecular charge-transfer (ICT) excitations. Single-crystal X-ray structures have been solved for two of the chromophores, one as its PF6- salt, revealing centrosymmetric packing arrangements (space groups Pbca and P1̅). Molecular quadratic nonlinear optical (NLO) responses have been determined directly by using hyper-Rayleigh scattering (HRS) with a 800 nm laser, and indirectly via Stark (electroabsorption) spectroscopy for the low energy absorption bands. The obtained static first hyperpolarizabilities β0 range from moderate to large: (9-140) × 10-30 esu from HRS in MeCN and (44-580) × 10-30 esu from the Stark data in PrCN. The magnitude of β0 increases upon either extending the π-conjugation length or replacing a methoxy with a tertiary amino electron donor substituent. Density functional theory (DFT) and time-dependent DFT calculations on selected tertiary amino chromophores confirm that the low energy absorptions have ICT character. Relatively good agreement between the simulated and experimental UV-vis absorption spectra is achieved by using the CAM-B3LYP functional with the 6-311G(d) basis set. The βtot values predicted by using DFT at the same level of theory are large ((472-1443) × 10-30 esu in MeCN). Both the theoretical and experimental results show that para-conjugation between Hq and electron donor fragments is optimal, and enlarging the Hq unit is inconsequential with respect to the molecular quadratic NLO response.

Single‐Crystal‐to‐Single‐Crystal Transition in an Enantiopure [7]Helquat Salt: The First Observation of a Reversible Phase Transition in a Helicene‐Like Compound

Here it is reported that crystals of an enantiopure [7]helquat salt undergo reversible thermal solid-solid phase transition at 404 K. Differential scanning calorimetry (DSC), capillary electrophoresis (CE), and X-ray diffraction analysis were used to unravel the mechanistic details of this process. The single-crystal-to-single-crystal course enabled direct monitoring of the structural changes by in situ variable-temperature X-ray diffraction, thus providing the first direct evidence of a solid phase transition in a helicene-like compound.

Dutch Resolution of a configurationally stable [5]helquat

Synthesis and nontrivial optical resolution of a helicene-like dication, helquat 1, has been accomplished. Starting with gram scale of the racemic helquat 1 sample, Dutch Resolution using family of 3 tartrate anions was key to achieve successful separation of M and P helical enantiomers of 1. Hundreds of milligrams of each enantiomer of this configurationally stable C2 -symmetric helquat have been obtained. Racemization barrier of 1 has been determined. To our knowledge this is the first report on Dutch Resolution performed with a helicene-like compound. Moreover, there are no literature precedents for Dutch Resolution of chiral quaternary ammonium cations.