Yatakemycin made on second try
The total synthesis of the bacterial natural product yatakemycin turned out to be more challenging than expected. Yatakemycin (shown) is the newest member of the duocarmycins, a promising class of antitumor compounds that act by alkylating DNA. It was discovered and structurally characterized last year by Yasuhiro Igarashi of Toyama Prefectural University, in Japan, and coworkers. But when Dale L. Boger and coworkers at Scripps Research Institute synthesized the proposed structure, their product turned out to be different from the natural product. They determined that a reactive indole thioacetate had to be changed to a more stable thiomethyl ester to reach the actual natural product. They weren't sure which enantiomer to make, so they synthesized both, and the (+)-enantiomer turned out to be the right one [J. Am. Chem. Soc., published online June 16, http://dx.doi.org/10.1021/ja0472735]. They believe yatakemycin's thiomethyl ester may bind to amines and proteins before or after DNA alkylation--a speculation they hope to clarify in future mechanistic studies.
Researchers have tracked the movement of molecules on a surface in real space by combining the atomic resolution of scanning tunneling microscopy and ultrafast femtosecond laser pulses. This technique holds promise for studying excited surface dynamics in unprecedented detail. Tony F. Heinz of Columbia University and colleagues excited a CO molecule adsorbed on a copper surface and studied the initial and final configurations of individual molecules [Science, published online June 24, http://www.sciencemag.org/cgi/content/abstract/1099770v1]. This work is important because surface diffusion processes are critical in crystal-growth techniques and in surface catalytic activity. Ordinarily, surface diffusion occurs under thermal equilibrium, but the adsorbate simply moves along the atomic rows of the surface. In this electronically excited situation, however, the CO both moves along the rows and jumps across them. The authors say the motions may arise from energy transfer between the adsorbate and substrate.
A "half-ribozyme" (target-activated ribozyme) system that has been developed can directly detect nucleic acids from hepatitis C virus (HCV) and perhaps other viruses as well. Hepatitis C, a chronic liver disease caused by HCV, is a serious public health problem. About 200 million people are infected worldwide, there is no vaccine, and there is no completely effective medicine. Screening for HCV is primarily by detection of anti-HCV antibodies, but false-positive and false-negative rates are significant. Methods that detect HCV RNA directly have fewer false results but are expensive. Barry Polisky and Scott D. Seiwert at Sirna Therapeutics, Boulder, Colo., and coworkers now report that the half-ribozyme system they developed directly detects HCV RNA, including natural sequence variants, and is as sensitive and inexpensive as immunoassays [Chem. Biol., 11, 807 (2004)]. Half-ribozyme detection should be applicable to other viral diagnostic applications as well, they note.
Switching the direction of the photocurrent in Shunsaku Kimura's new molecular photodiode system is as simple as changing the wavelength of irradiating light [Science, 304, 1944 (2004)]. To create this switchable system, Kimura and his colleagues at Japan's Kyoto University took advantage of the dipole moment that runs from the C-terminus to the N-terminus of a helical peptide and turned the helices into tiny wires. They designed two types of helical peptide: One is equipped with the photosensitizer N-ethylcarbozolyl (ECz) at the C-terminus, and the other carries a photosensitive tris(2,2´-bipyridine)ruthenium(II) complex at its N-terminus. A disulfide group at the terminus opposite the photosensitizer anchors the peptides in opposing directions on a gold substrate. Together they form a bicomponent monolayer, but Kimura reports that both types of helical wire work independently. Irradiating the system at 351 nm excites the ECz moiety and generates an anodic photocurrent where electrons flow toward the gold substrate. Changing the irradiating wavelength to 459 nm excites the ruthenium complex, thereby generating a cathodic photocurrent where the electrons flow in the opposite direction.
The number of binary metal polyazide compounds, M(N3)n, has jumped recently, following reports of new syntheses by several research teams. The latest examples are the first binary group 4 polyazides prepared and characterized by Ralf Haiges and Karl O. Christe of the University of Southern California and coworkers [Angew. Chem. Int. Ed., 43, 3148 (2004)]. The researchers synthesized Ti(N3)4 by reacting TiF4 with (CH3)3SiN3 in acetonitrile at room temperature. Further treatment of Ti(N3)4 with one or two equivalents of [P(C6H5)4]N3 led to formation of [P(C6H5)4][Ti(N3)5] and [P(C6H5)4]2[Ti(N3)6], respectively. The latter compounds are less shock sensitive than the tetraazide, and the crystal structure of the dianion [Ti(N3)6]2 (shown) reveals bent TiNN bonding, which is typical for polyazides. In contrast, a theoretical study has predicted that Ti(N3)4 should be tetrahedral with unprecedented linear MNN bonding. The USC researchers could not obtain single crystals for a structure determination, but the IR and Raman spectra indicate that solid Ti(N3)4 is polymeric with bent TiNN units. Aside from their structural interest, the polyazides are important as highly energetic materials or for electronics applications.