Effective Synthesis and Antifouling Activity of Dolastatin 16 Derivatives.

Some derivatives of dolastatin 16, a depsipeptide natural product first obtained from the sea hare Dolabella auricularia, were synthesized through second-generation synthesis of two unusual amino acids, dolaphenvaline and dolamethylleuine. The second-generation synthesis enabled derivatizations such as functionalization of the aromatic ring in dolaphenvaline. The derivatives of fragments and whole structures were evaluated for antifouling activity against the cypris larvae of Amphibalanus amphitrite. Small fragments inhibited the settlement of the cypris larvae at potent to moderate concentrations (EC50 = 0.60-4.62 µg/mL), although dolastatin 16 with a substituent on the aromatic ring (24) was much less potent than dolastatin 16.

Effects of citalopram on jaw-closing muscle activity during sleep and wakefulness in mice.

In this study, we investigated the effects of chronic administration of the selective serotonin reuptake inhibitor (SSRI) citalopram on sleep/wake cycles and masseter (jaw-closing) muscle electromyogram (EMG) activity over a 24-h period. From the dark to the light period, the times of wakefulness decreased, while those of non-rapid eye movement (NREM) and REM sleep increased. Citalopram did not induce major alterations in the temporal changes of sleep-wake distributions, except for leading to a decrease in the time of NREM sleep during the light period and an increase in the durations of REM sleep episodes. Moreover, citalopram did not modify mean masseter EMG activity during any of the vigilance states and did not affect the temporal changes related to the shifts between dark/light periods. However, citalopram increased the time engaged in masseter EMG activation during NREM sleep in the second and the first halves of the dark and light periods, respectively. These results suggest that chronic citalopram treatment does not affect the temporal changes of sleep-wake distributions, but has a limited facilitatory influence that fails to increase the number of epochs of high levels of masseter muscle activation.

Dark/light transition and vigilance states modulate jaw-closing muscle activity level in mice.

Bruxism is associated with an increase in the activity of the jaw-closing muscles during sleep and wakefulness. However, the changes in jaw-closing muscle activity across states of vigilance over a 24-h period are unclear. In this study, we investigated the effects of dark/light transition and sleep/wake state on EMG activity of the masseter (jaw-closing) muscle in comparison with the activity of the upper trapezius muscle (a neck muscle) over a 24-h period in mice. The activities of the masseter and neck muscles during wakefulness were much greater than during non-REM and REM sleep. In contrast, the activities of both muscles slightly, but significantly, decreased during the transition period from dark to light. Histograms of masseter activity during wakefulness and non-REM sleep showed bimodal distributions, whereas the neck muscle showed unimodal activation in all states. These results suggest that the activities of jaw-closing and neck muscles are modulated by both sleep/wake state and dark/light transition, with the latter being to a lesser degree. Furthermore, even during non-REM sleep, jaw-closing muscles display bimodal activation, which may contribute to the occurrence of exaggerated aberrant muscle activity, such as sleep bruxism.

Formation of Multicomponent Star Structures at the Liquid/Solid Interface.

To demonstrate key roles of multiple interactions between multiple components and multiple phases in the formation of an uncommon self-assembling pattern, we present here the construction of a porous hexagonal star (h-star) structure using a trigonal molecular building block at the liquid/solid interface. For this purpose, self-assembly of hexaalkoxy-substituted dehydrobenzo[12]annulene derivatives DBA-OCns was investigated at the tetradecane/graphite interface by means of scanning tunneling microscopy (STM). Monolayer structures were significantly influenced by coadsorbed tetradecane molecules depending on the alkyl chains length (C13-C16) of DBA-OCn. However, none of DBA-OCn molecules formed the expected trigonal complexes, indicating that an additional driving force is necessary for the formation of the trigonal complex and its assembly into the h-star structure. As a first approach, we employed the "guest induced structural change" for the formation of the h-star structure. In the presence of two guest molecules, nonsubstituted DBA and hexakis(phenylethynyl)benzene which fit the respective pores, an h-star structure was formed by DBA-OC15 at the tetradecane/graphite interface. Moreover, a tetradecane molecule was coadsorbed between a pair of alkyl chains of DBA-OC15, thereby blocking the interdigitation of the alkyl chain pairs. Therefore, the h-star structure results from the self-assembly of the four molecular components including the solvent molecule. The second approach is based on aggregation of perfluoroalkyl chains via fluorophilicity of DBA-F, in which the perfluoroalkyl groups are substituted at the end of three alkyl chains of DBA-OCn via p-phenylene linkers. A trigonal complex consisting of DBA-F and three tetradecane molecules formed an h-star structure, in which the perfluoroalkyl groups that orient into the alkane solution phase aggregated at the hexagonal pore via fluorophilicity. The present result provides useful insight into the design and control of complex molecular self-assembly at the liquid/solid interface.

Functionalized surface-confined pores: guest binding directed by lateral noncovalent interactions at the solid-liquid interface.

We present here the construction of self-assembled two-dimensional (2D) molecular networks that contain pores equipped with functional groups that promote guest-specific binding at the liquid/solid interface. For this purpose, a dehydrobenzo[12]annulene (DBA) derivative, DBA-F, having perfluoroalkyl groups at the end of the three alternating alkoxy chains connected by para-phenylene linkers was synthesized. For comparison DBA-H, having the same carbon backbone without fluorine substituents, was also prepared. STM observations revealed that these molecules formed porous 2D networks whose pores were decorated with either fluoroalkane or simple alkane perimeters. Hexakis(phenylethynyl)benzene, HPEB, and its octadecafluoro derivative, HPEB-F surrounded by 18 fluorine atoms, were employed as planar guest molecules of suitable size. The fluoroalkane-lined pores present in the network of DBA-F exhibited good binding ability toward both guest molecules via fluorophilicity and electrostatic interaction, respectively. In contrast the binding ability of the alkane-lined pore of the network of DBA-H for the fluorinated guest HPEB-F was poor as a result of weaker electrostatic interaction. Interestingly, with HPEB as a guest, this network underwent a periodical structural deformation through an induced-fit mechanism to form a superlattice structure consisting of free and occupied pores. These observations are discussed based on modeling experiments using molecular mechanics and quantum chemical methods to elucidate the roles of lateral noncovalent interactions and size matching between the pore and the guest molecules used for 2D guest binding.

Porous molecular networks formed by the self-assembly of positively-charged trigonal building blocks at the liquid/solid interfaces.

Tris-(2-hydroxybenzylidene)triaminoguanidinium salts having six alkyl chains with proper spacing served as new molecular building blocks for the formation of porous honeycomb networks by van der Waals interaction between interdigitated alkyl chains at the liquid/graphite interfaces.

Temperature-induced structural phase transitions in a two-dimensional self-assembled network.

Two-dimensional (2D) supramolecular self-assembly at liquid-solid interfaces is a thermodynamically complex process producing a variety of structures. The formation of multiple network morphologies from the same molecular building blocks is a common occurrence. We use scanning tunnelling microscopy (STM) to investigate a structural phase transition between a densely packed and a porous phase of an alkylated dehydrobenzo[12]annulene (DBA) derivative physisorbed at a solvent-graphite interface. The influence of temperature and concentration are studied and the results combined using a thermodynamic model to measure enthalpy and entropy changes associated with the transition. These experimental results are compared to corresponding values obtained from simulations and theoretical calculations. This comparison highlights the importance of considering the solvent when modeling porous self-assembled networks. The results also demonstrate the power of using structural phase transitions to study the thermodynamics of these systems and will have implications for the development of predictive models for 2D self-assembly.

Solvent-induced homochirality in surface-confined low-density nanoporous molecular networks.

Induction of chirality in achiral monolayers has garnered considerable attention in the recent past not only due to its importance in chiral resolutions and enantioselective heterogeneous catalysis but also because of its relevance to the origin of homochirality in life. In this contribution, we demonstrate the emergence of macroscopic chirality in multicomponent supramolecular networks formed by achiral molecules at the interface of a chiral solvent and an achiral substrate. The solvent-mediated chiral induction provides a simple, efficient, and versatile approach for the fabrication of homochiral surfaces using achiral building blocks.