A new tri-orthogonal strategy for peptide cyclization

A solid phase tri-orthogonal protection/cleavage strategy that uses acidic, basic, and neutral conditions is described. Strategically protected alpha-azido-gamma-9-fluorenylmethyl-L-glutamate (1) and alpha-azido-epsilon-N-Fmoc-L-lysine (2) were incorporated into growing peptides on Wang resin using a novel azide protection strategy. These residues, separated by 1-3 monomers, were deprotected at the side chains and cyclized via lactam formation. The N-terminus was further functionalized to extend the chain. This method represents a straightforward protocol for peptide cyclization on solid support.     

Gravitational waves and red shifts: A space experiment for testing relativistic gravity using multiple time-correlated radio signals

We describe an experimental technique for detecting extremely low-frequency pulses of gravitational radiation ( _GW 1–10 mHz) originating from collapsing supermassive objects (M 10⁶–10⁷ m ) occurring anywhere in the universe. Our technique is the natural outgrowth of a previous gravitational space mission. The novelty of our approach is in placing a highly stable hydrogen maser onboard a deep-space probe that controls a transmitter sending signals to earth. The spacecraft also includes a doppler transponder operating in the conventional two-way mode. Doppler tracking using simultaneously acquired one- and two-way information both on the spacecraft and at the earth station provides four time-records of frequency fluctuations. A single gravitational disturbance manifests itself as a uniquely determined pulse sequence in the two or more data sets whose amplitudes and arrival times depend on a single parameter. The repetition of the signal and the noises in the data can be used in a filtering scheme to improve the amplitude sensitivity by a factor of about 6 in amplitude (36 in energy). We believe the most likely of these gravitational pulse events occurring frequently enough to be detected (more than once per year) will come from the formation of black holes in the cores of ordinary spiral galaxies. We propose a technologically feasible and realistic space mission, using the above technique, to measure two aspects of gravitation with the same experimental equipment. The spaceflight begins in a highly eccentric earth orbit to measure the gravitational red shift and the second-order doppler effects to an accuracy of 5 parts in 10⁶; at this level significant new tests of nonmetric theories of gravity are possible. Later, the spacecraft is sent into a heliocentric orbit to distances beyond 6 AU to search for gravitational radiation.     

A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B

Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11–17 steps, 1.5–2.9% yield). Thus, to access this compound more efficiently, we herein present a concise and significantly improved total synthesis of the natural product. Our short synthesis relies on two key cyclization steps to assemble the central scaffold: isoquinoline formation via an ethynyl-imino cyclization and an intramolecular Friedel-Crafts reaction to form the furanone.     

Energy dependence of the ionization probability of sputtered Cu and Ni

Despite its great sensitivity, the usefulness of secondary ion mass spectrometry (SIMS) for many applications has been limited by an inadequate understanding of the probability of sputtering an atom in an ionized state. To determine this ionization probability for clean Cu and Ni surfaces, I have measured the energy distribution of sputtered neutrals and ions by quadrupole mass filtering and retarding potential analysis using potential modulation differentiation. Analysis of sputtered neutrals was accomplished by electron impact ionization. Because the neutrals outnumber the ions by at least two orders of magnitude, the ratio of sputtered ions to neutrals is an accurate measure of the ionization probability. For energies below 20 eV the dependence of the ionization probability on energy goes as P(E) α Eⁿ, where n = 0.65 for clean Cu. The absorption of oxygen on the Cu surface increases the total ion yield while causing a reduction in the value of the exponent n. Similar results are found for nickel, where n = 0.54 for the clean surface.     

Studies on the conformation of α-arylcinnamic acids and their esters: Crystal structures of methyl (E)-2,3-bis(3,4-dimethoxyphenyl)propenoate and methyl (Z)-2,3-bis(3,4-dimethoxyphenyl)propenoate

The conformations of stereoisomers of -arylcinnamic acids and their esters are discussed based on crystal structures of the E and Z forms of 2,3-bis(3,4-dimethoxyphenyl)propenoic acid and its methyl ester. In the E forms of the cinnamic acid and the cinnamic acid ester, the plane of the -aryl substituent is approximately perpendicular to that of the rest of the molecule. In the Z forms the plane of the carboxyl or methoxycarbonyl group is approximately perpendicular to that of the ethylenic group, and both the aromatic group planes are significantly twisted out of the ethylenic group plane. Crystal structures of methyl (E)-2,3-bis(3,4-dimethoxyphenyl)propenoate (space group P2₁/n with a = 8.1697(5), b = 11.3882(9), c = 19.7766(9) Å, = 90.058(4)°, V = 1840.0(2) ų, and Z = 4), monoclinic methyl (Z)-2,3-bis(3,4-dimethoxyphenyl)propenoate (space group P2₁/n with a = 11.183(2), b = 5.640(2), c = 29.737(7) Å, = 99.19(2)°, V = 1851.4(9) ų, and Z = 4), and orthorhombic methyl (Z)-2,3-bis(3,4-dimethoxyphenyl)propenoate (space group P2₁2₁2₁ with a = 8.849(4), b = 24.288(9), c = 8.734(3) Å, V = 1877(1) ų, and Z = 4) are reported.     

Picosecond pulses from a cryogenically cooled, composite amplifier using Yb:YAG and Yb:GSAG

A cryogenic Yb amplifier using two laser materials, Gd3Sc2Al3O12 and Y3Al5O12 (YAG), has been used to obtain 70 W average power at 5 kHz pulse repetition frequency; the output was compressed to 1.6 ps, compared with an input compressible to 1.4 ps. The gain broadening obtained by combining two media enables shorter pulses than using Yb:YAG alone but retains the power-scaling advantages of cryogenic Yb:YAG.