Molecular Switching in Confined Spaces: Effects of Encapsulating the DHA/VHF Photo-Switch in Cucurbiturils.

Confinement of reactive chemical species uniquely affects chemical reactivity by restricting the physical space available and by restricting access to interactions with the solvent. In Nature, for example, confined protein binding pockets govern processes following photoisomerization reactions and the isomerizations themselves. Here we describe the first example of a dihydroazulene/vinylheptafulvene (DHA/VHF) photo-switch functioning in water, and we show how its switching behavior is strongly influenced by supramolecular interactions with a series of cucurbit[n]uril (CB) host molecules. In CB7 inclusion complexes, the kinetics of the thermal VHF-to-DHA back-reaction is accelerated, while in CB8 inclusion complexes, the kinetics is slowed down as compared to the free photo-switch. The effect of the CB encapsulation of the photo-switch can be effectively canceled by introducing a guest that binds the CB more strongly. According to DFT calculations, a stabilization of the reactive s-cis VHF conformer relative to the s-trans VHF appears to be a contributing factor responsible for the accelerated back-reaction when encapsulated in CB7.

On the condensed phase ring-closure of vinylheptafulvalene and ring-opening of gaseous dihydroazulene.

Dihydroazulenes are interesting because of their photoswitching behavior. While the ring-opening to vinylheptafulvalene (VHF) is light induced, the back reaction is known to proceed thermally. In the present paper, we show the first gas phase study of the ring-opening reaction of 2-phenyl-1,8a-dihydroazulene-1,1-dicarbonitrile (Ph-DHA) by means of time-resolved photoelectron spectroscopy which permits us to follow the ring-opening process. Moreover, we investigated s-trans-Ph-VHF in a series of transient absorption experiments, supported by ab initio computations, to understand the origin of the absence of light-induced ring-closure. The transient absorption results show a biexponential decay governed by a hitherto unknown state. This state is accessed within 1-2 ps and return to the ground state is probably driven through a cis-trans isomerization about the exocyclic C1═C2 double bond. The rapid decrease in potential energy disfavors internal rotation to s-cis-Ph-VHF, the structure that would precede the ring-closure reaction.

Diastereoselective synthesis of novel heterocyclic scaffolds through tandem Petasis 3-component/intramolecular Diels-Alder and ROM-RCM reactions.

A high-yielding, stereoselective and extraordinarily complexity-generating Petasis 3-component/intramolecular Diels-Alder reaction has been developed. In combination with ROM-RCM, rapid access to complex sp3-rich heterocyclic scaffolds amenable to subsequent functionalization and library synthesis is provided.

Acyclic, achiral enamide nucleoside analogues. The importance of the C=C bond in the analogue for its ability to mimic natural nucleosides.

The conformations of an acyclic, achiral enamide thymidine analogue 1 have been studied by model building and geometry calculations, as well as by NMR NOE and UV experiments. The results indicate that there are no significant barriers to rotation around any of the sigma bonds, in particular the N1-C1' enamide bond, and that the analogue should be able to accommodate conformations that mimic the conformations of natural nucleosides in A- and B-type helices quite well. For comparison the saturated analogue 2 has been prepared and built into oligonucleotides. It is shown that incorporation of 2 in oligonucleotides results in a much larger depression of the melting temperature (deltaTm -10 to -12.5 degrees C) than does incorporation of 1 (deltaTm -5 to -6.5 degrees C).

Preparation and antiviral properties of new acyclic, achiral nucleoside analogues: 1- or 9-[3-hydroxy-2-(hydroxymethyl)prop-1-enyl]nucleobases and 1- or 9-[2,3-dihydroxy-2-(hydroxymethyl)propyl]nucleobases.

Acyclic, achiral nucleoside derivatives 1b-e of adenine, cytosine, 5-methylcytosine, and guanine, containing a 3-hydroxy-2-(hydroxymethyl)prop-1-enyl group on N-1 or N-9, have been prepared analogously to the previously described thymine derivative 1a. In contrast to the adenine and guanine derivatives, the cytosine derivative 9 was unstable, and was obtained in a low yield due to side reactions. These include cleavage of the propenyl group from the base, and the formation of a bicyclic compound. The thymine derivative, although stable under neutral conditions, likewise underwent a reversible cyclization reaction (Michael addition) in the presence of acids or bases. The 5-methylcytosine derivative was stable under neutral and basic conditions. Four other nucleoside derivatives 26a-d containing a 2,3-dihydroxy-2-(hydroxymethyl)propyl group on N-1 or N-9, three of which are new, have likewise been prepared. All compounds were evaluated as antiviral agents against HIV-1 and HSV-1 but were devoid of antiviral activity.