Gebhard Haberhauer

A Bridged Azobenzene Derivative as a Reversible, Light‐Induced Chirality Switch

Photochromic molecules, which can be switched reversibly between two isomeric forms having different structures and properties, are of great interest for the development of optical memory devices, and molecular motors and machines. A prominent example of a light-induced switching process is the trans!cis isomerization of azobenzene and its derivatives. The high-amplitude change between the stretched trans form and the compact cis isomer, the relatively high reversibility, and the photostability which allows a multitude of switching cycles, make azobenzene derivatives among the most frequently used switching devices. A closer look at the switching process of azobenzene shows that the transition of the trans to the cis isomer implies not only a structural change but also the generation of helical chirality; that is, two enantiomeric cis isomers are formed (Scheme 1). The development of a unidirectional switching process that takes place exclusively between the achiral, planar trans isomer and only one of the chiral cis isomers would extend the range of applications of azobenzenes tremendously. Such a process would provide a switch with which, in addition to the amplitude change, a useful helical chirality element can be switched on and off. Azobenzene derivatives have been used for several switching processes in which chirality is critical, for example in molecular scissors, switchable peptides, and chiral nematic phases, and for the stabilization of helical structures. 11] However, the unidirectional switching of the azobenzene unit and thus a targeted use of the helical chirality element has not been possible so far. The use of circularly polarized light leads to a partially unidirectional switching of the azobenzene unit; however, in solution this is followed by fast racemization of the cis isomers. Only in the case of tetrasubstituted alkenes with sterically demanding substituents could unidirectional light-induced switching be achieved without subsequent racemization. 14] By implementation of a chiral clamp this could be, in principle, also achieved with azobenzenes (2 in Scheme 1). The clamp should be flexible enough to allow a strong amplitude change upon trans!cis isomerization, but should simultaneously destabilize one of the cis conformations (here the cis-(M) isomer) to such an extent that only one isomer (here the cis-(P)-isomer) is present in solution under standard conditions. As we had already succeeded in accomplishing a unidirectional switching of bipyridine derivatives by means of chiral cyclic imidazole peptides, we decided to use the chiral clamp 3 also for the synthesis of the unidirectionally switchable azobenzene 2 (Scheme 2). Simple alkylation of 3 with dibromide 4 using Cs2CO3 as the base in acetonitrile provided the desired azo compound 2 in 22% yield. To clarify whether the azo compound 2 combines both desired properties—high amplitude change along with the energetic discrimination of one of the cis isomers—the structures of trans1, trans-2, cis-(P)-1, cis-(P)-2, and cis-(M)-2 were determined by geometry optimization using B3LYP and the 6-31G* basis set. We found that the difference in energy between trans-1 and cis-(P)-1, which amounts to 63.4 kJmol , is similar to that between trans-2 and cis-(P)-2 (57.7 kJmol ) (Table 1). Hence, also for azobenzene 2, a trans!cis isomerization should be possible under standard conditions. The high amplitude change found in azobenzene 1, which is reflected, for example, in the change of the C2–C2’ and C5–C5’ distances, is also present in the switching process from trans2 to cis-(P)-2. For both azobenzenes (1 and 2), the trans!cis isomerzation results in a reduction of the C5–C5’ distance by Scheme 1. Light-induced switching of azobenzene (1; bidirectional) and of the chiral azobenzene derivative 2 (unidirectional).

Synthesis of a new class of imidazole-based cyclic peptides.

A new class of cyclic peptides based on dipeptidyl imidazoles is presented. Their structure consists of imidazole units alternating with std. amino acid residues (Val, Phe, b-aminoalanine) and resembles naturally occurring marine cyclopeptides such as westiellamide and ascidiacyclamide.

Control of planar chirality: the construction of a copper-ion-controlled chiral molecular hinge.

The control of the mechanical motion of single molecules by external stimuli is a rapidly growing scientific area of great contemporary interest. Until now, a variety of molecular devices, such as motors, rotors, shuttles, ratchets, and tweezers, have been developed. A crucial point is the construction of synthetic molecular machines that utilize—in analogy to their macroscopic pendants—the directional and synchronized movements of smaller parts. In these systems an external stimulus triggers the controlled, large-amplitude or directional mechanical motion of one component relative to another which results in a task being performed. Especially useful for this purpose are molecular devices in which unidirectional rotations are controlled by changes of configuration or conformation. Examples of such systems are unidirectional rotors rotating around single or double bonds, catenanes showing unidirectional rotary motion, and molecular scissors. In the latter, irradiation triggers the opening and closing of the blades with an alteration of the angle between the blades from approximately 98 to 588. A unidirectional open–close mechanism with even higher relative amplitudes (around 1808) is possible with a hinge. The two flexible wings of the hinge (blue elements in Scheme 1) can be opened and closed by motion about the rotation axis (red element) in only one direction (area framed in green in Scheme 1); opening in the opposite direction is not possible (area framed in red). Closing at the hinge also occurs only in one direction; a flipping “inside out” (overrotation), a closing motion extending from a dihedral angle of 1808 to an angle of 3608, is prevented by a fixing bracket (black element). As a basis for the design of a molecular hinge with a unidirectional open–close motion we chose the 2,2’-biypridine unit (Scheme 1). Here the pivot is the C C bond between the two pyridine units. In the uncomplexed state, 2,2’-bipyridine exhibits an N-C-C-N dihedral angle of 1808. This value changes to 08 when the bipyridine unit forms a complex with, for example, a copper(II) ion. The substituents para to the nitrogen atoms undergo a relative amplitude motion of 1808. The driving force for the closing process is the formation of the copper(II) bipyridine complex, whereas the driving force for the opening is the repulsive interaction between the hydrogens in positions 3 and 3’ of the bipyridine in the absence of copper(II) ions. The removal of the copper(II) ions can be achieved chemically by the addition of an even stronger Cu-complexing agent such as cyclam. To prevent an overrotation of the flexible pyridine unit, a medium-sized bridge is introduced, thus making the entire molecule planar chiral when it is not complexed. Consequently, the differentiation between the desired and the undesired open–close motion can be reduced to the selective formation of only one

A Molecular Four‐Stroke Motor

One of the most challenging aspect in the construction of molecular analogues of mechanical devices is the creation of synthetic molecular motors which utilize the unidirectional movements of smaller parts and which thus should be able to perform a physical task. 6] Almost all synthetic molecular motors described to date are rotary motors. The axis of the rotation in these motors is a single or a double chemical bond or a mechanical bond, and is coincident with the center where energy is transformed into mechanical work. 8] As their flexible parts remain the same size during a cycle, they perform a simple rotation like that found in the F1-ATPase in nature. Thus they are designed to transport an attached molecule in a rotation movement of 3608, but they are not able to transport surrounding molecules in one definite direction—they just distribute them in a circular movement. Herein we present a synthetic molecular motor that has a motion sequence which resembles the movement of motile cilia. Motile cilia are widely found in nature and, through their beating movement, are used either for the transport of particles and surrounding medium or for the locomotion of cells. As our motor works in a similar way, it should automatically push surrounding molecules in a definite direction during a four-stroke cycle. The essential principle is the spatial separation of the area where chemical energy is transformed into mechanical work, from the rotation axis. The design and the concept of our molecular four-stroke motor is illustrated in Figure 1. The central part of the motor is a chiral clamp, which we have already successfully used for the control of unidirectional movements and for the design of a molecular chirality pendulum. 13] Through the chiral clamp, the clamp-bound pyridine rings of the bipyridine units are fixed in a cycle, and thus adopt a P configuration with respect to each other. One of the bipyridine units carries a light-switchable azobenzene unit and is the chemically driven pushing blade of the motor. The other bipyridine unit acts as a stopper and controls the direction of the movement. An alternating stimulation of the whole blade and the azobenzene unit of the blade leads in sum to a 3608 rotation of the phenyl group of the azobenzene unit around a virtual axis. Let s consider the states of the rotation process in detail. The molecule trans-(P)-1 corresponds to state I of the rotation cycle. As non-complexed 2,2’-biypridine units have an N-C-CN dihedral angle of about 1808, the arm of the blade (azobenzene unit) and the arm of the stopper (bromine) in trans-(P)-1 have a definite relative spatial configuration (the P configuration). The addition of salts containing metal ions, such as Zn, leads to a complexation of the 2,2’bipyridines and thus the complex trans-(M)-1*Zn2 4+ is formed which represents state IV of the rotation cycle. As metalcomplexed 2,2’-bipyridines have a N-C-C-N dihedral angle of around 08, the transition from state I to state IV is accompanied by a movement of the blade. The reversibility of this movement—the backward movement of the blade—is achieved chemically by the addition of cyclam which complexes the Zn ions better than the bipyridine units of 1. The second important process for the cycle is the light-induced switching of the azo group. In the trans configuration of the azo group (state I) the para-bonded hydrogen atom points away from the bipyridine unit whereas in the cis configuration (state II) it is orientated toward the bipyridine unit. Thus, the trans!cis isomerization of the azobenzene group triggered by UV irradiation (l = 355 nm) is accompanied by a folding of the blade. This transition (I!II) is also reversible. The reverse state change from II!I takes place on a brief irradiation of the cis isomer with visible light. The whole rotation cycle consists of an alternating combination of the rotation movement of the blade and its light-induced folding and opening: Exposure of trans-(P)-1 to UV light at 20 8C induces trans!cis isomerization and results in a transition from state I to state II (first stroke). The addition of Zn leads to a movement of the blade (second stroke) and the complex cis-(M)-1*Zn2 4+ representing state III in the cycle is formed. This stroke resembles the recovery stroke of motile cilia. The third stroke (III!IV; opening of the blade) is the cis!trans back isomerization to trans-(M)-1*Zn2 induced by visible light. The backward movement of the opened blade triggered by the addition of cyclam (fourth stroke) resembles the effective stroke of motile cilia. As the opened blade can push more molecules in one direction (fourth stroke) than the closed blade in the other (second stroke) there should be a net transport of the surrounding molecules in one direction. An important requirement for the motor is that the movement of the blade must proceed unidirectionally. To check if this is true for the motor 1, the reference compound 2 was investigated. The only difference between 1 and 2 is the absence of the azobenzene unit in molecule 2. In principle there are two possible ways for the movement of the blade. In [*] Prof. Dr. G. Haberhauer Institut f r Organische Chemie, Fakult t f r Chemie Universit t Duisburg-Essen Universit tsstrasse 7, 45117 Essen (Germany) E-mail: gebhard.haberhauer@uni-due.de

Copper(II) Coordination Chemistry of Westiellamide and Its Imidazole, Oxazole, and Thiazole Analogues

The copper(II) coordination chemistry of westiellamide (H(3)L(wa)), as well as of three synthetic analogues with an [18]azacrown-6 macrocyclic structure but with three imidazole (H(3)L(1)), oxazole (H(3)L(2)), and thiazole (H(3)L(3)) rings instead of oxazoline, is reported. As in the larger patellamide rings, the N(heterocycle)-N(peptide)-N(heterocycle) binding site is highly preorganized for copper(II) coordination. In contrast to earlier reports, the macrocyclic peptides have been found to form stable mono- and dinuclear copper(II) complexes. The coordination of copper(II) has been monitored by high-resolution electrospray mass spectrometry (ESI-MS), spectrophotometric and polarimetric titrations, and EPR and IR spectroscopies, and the structural assignments have been supported by time-dependent studies (UV/Vis/NIR, ESI-MS, and EPR) of the complexation reaction of copper(II) with H(3)L(1). Density functional theory (DFT) calculations have been used to model the structures of the copper(II) complexes on the basis of their spectroscopic data. The copper(II) ion has a distorted square-pyramidal geometry with one or two coordinated solvent molecules (CH(3)OH) in the mononuclear copper(II) cyclic peptide complexes, but the coordination sphere in [Cu(H(2)L(wa))(OHCH(3))](+) differs from those in the synthetic analogues, [Cu(H(2)L)(OHCH(3))(2)](+) (L = L(1), L(2), L(3)). Dinuclear copper(II) complexes ([Cu(II) (2)(HL)(mu-X)](+); X = OCH(3), OH; L = L(1), L(2), L(3), L(wa)) are observed in the mass spectra. While a dipole-dipole coupled EPR spectrum is observed for the dinuclear copper(II) complex of H(3)L(3), the corresponding complexes with H(3)L (L = L(1), L(2), L(wa)) are EPR-silent. This may be explained in terms of strong antiferromagnetic coupling (H(3)L(1)) and/or a low concentration of the dicopper(II) complexes (H(3)L(wa), H(3)L(2)), in agreement with the mass spectrometric observations.

Planarized Intramolecular Charge Transfer: A Concept for Fluorophores with both Large Stokes Shifts and High Fluorescence Quantum Yields.

Fluorophores were successfully used in several areas of chemistry and biochemistry. For many purposes, however, it is necessary that the fluorescence compound features a high fluorescence quantum yield as well as a large Stokes shift. The latter is, for example, achieved by the use of a twisted intramolecular charge-transfer (TICT) compound, which shows a twisted geometry in the excited state. However, the higher the twisting is, the lower becomes in general the fluorescence quantum yield as the resulting emission from the twisted state is forbidden. In order to escape this dilemma, we propose the model of planarized intramolecular charge-transfer (PLICT) states. These compounds are completely twisted in the ground states and planar in the excited states. By means of quantum chemical calculations (time-dependent (TD)-B3LYP and CC2) and experimental studies, we could demonstrate that 1-aminoindole and its derivatives form photoinduced PLICT states. They show both very large Stokes shifts (ν˜ =9000-13 500 cm(-1) , i.e., λ=100-150 nm) and high fluorescence quantum yields. These characteristics and their easy availability starting from the corresponding indoles, make them very attractive for the use as optical switches in various fields of chemistry as well as biological probes.

Dimerization of Two Alkyne Units: Model Studies, Intermediate Trapping Experiments, and Kinetic Studies

By means of high level quantum chemical calculations (B2PLYPD and CCSD(T)), the dimerization of alkynes substituted with different groups such as F, Cl, OH, SH, NH2, and CN to the corresponding diradicals and dicarbenes was investigated. We found that in case of monosubstituted alkynes the formation of a bond at the nonsubstituted carbon centers is favored in general. Furthermore, substituents attached to the reacting centers reduce the activation energies and the reaction energies with increasing electronegativity of the substituent (F > OH > NH2, Cl > SH, H, CN). This effect was explained by a stabilizing hyperconjugative interaction between the σ* orbitals of the carbon-substituent bond and the occupied antibonding linear combination of the radical centers. The formation of dicarbenes is only found if strong π donors like NH2 and OH as substituents are attached to the carbene centers. The extension of the model calculations to substituted phenylacetylenes (Ph-C≡C-Y) predicts a similar reactivity of the phenylacetylenes: F > OCH3 > Cl > H. Trapping experiments of the proposed cyclobutadiene intermediates using maleic anhydride as dienophile as well as kinetic studies confirm the calculations. In the case of phenylmethoxyacetylene (Ph-C≡C-OCH3) the good yield of the corresponding cycloaddition product makes this cyclization reaction attractive for a synthetic route to cyclohexadiene derivatives from alkynes.

An azobenzene unit embedded in a cyclopeptide as a type-specific and spatially directed switch.

By embedding an azobenzene unit into a chiral scaffold, switching of azobenzene from the trans-(P) isomer to the cis-(P) isomer and back was achieved (black arrows in picture). The embedding leads to a flipping process in which the phenyl rings can only move directly towards one another in the switching process.

Strongly underestimated dispersion energy in cryptophanes and their complexes

Cryptophanes, composed of two bowl-shaped cyclotriveratrylene subunits linked by three aliphatic linker groups, are prototypal organic host molecules which bind reversibly neutral small guest compounds via London forces. The binding constants for these complexes are usually measured in tetrachloroethane and are in the range of 10(2)-10(3) M(-1). Here we show that tetrachloroethane is--in contrast to the scientific consensus--enclosed by the cryptophane-E cavity. By means of NMR spectroscopy we show that the binding constant for CHCl3@cryptophane-E is in larger solvents two orders of magnitudes higher than the one measured before. Ab initio calculations reveal that attractive dispersion energy is responsible for high binding constants and for the formation of imploded cryptophanes which seem to be more stable than cryptophanes with empty cavities.

A very stable complex of a modified marine cyclopeptide with chloroform

Noncovalent interactions play a pivotal role in molecular recognition. These interactions can be subdivided into hydrogen bonds, cation-π interactions, ion pair interactions and London dispersion forces. The latter are considered to be weak molecular interactions and increase with the size of the interacting moieties. Here we show that even the small chloroform molecule forms a very stable complex with a modified marine cyclopeptide. By means of high-level quantum chemical calculations, the size of the dispersive interactions is calculated; the dispersion energy (approximately -40 kcal mol⁻¹) is approximately as high as if the four outer atoms of the guest form four strong hydrogen bonds with the host. This strong binding of chloroform to a modified marine cyclopeptide allows the speculation that the azole-containing cyclopeptides-haloform interaction may play some biological role in marine organisms such as algae.