Molecule-Responsive Fluorescent Sensors of α-Helix Peptides Bearing α-Cyclodextrin, Pyrene and Nitrobenzene Units in Their Side Chains

-Helix peptides bearing one unit of -cyclodextrin (-CD), one unit of pyrene and one unit of nitrobenzene (NB) in their side chains have been designed and synthesized as novel molecule-responsive devices.In both the CD-peptides, -PR17 and -PL17, the NB unit is separated from the CD unit by two turns of the helix. Two reference peptides (PL17, and -P17,) have also been synthesized. The circular dichroism studies in the peptide absorption region (200–250 nm)of -PR17 and -PL17 suggestthat the CD-peptides form stable-helixstructures (83–77%), which was destabilized by accommodating guest molecules (e.g., n-pentanol) into the CD cavity. It suggests that formation of intramolecular host–guest(CD–NB) complex stabilized thehelical structure and exogenous guest molecule excluded the appending NB moiety from inside to outside of the CD cavity, thereby causing destabilization of the helical structure and increasing the random coil content. The ICD spectra of the peptides in the pyrene and nitrobenzene absorption region (250–40 nm) suggest that NB forms inclusion complex with CD. The fluorescence studies revealed that the fluorescence of the pyrene unit is quenched by the NB unit in -PR17 and -PL17. The fluorescence intensity increases with increasing guest concentration for the CD-peptides.This guest-responsiveenhancement in the fluorescence intensity can be explained in terms of increased distance between the pyrene and NB moieties, which is caused by exclusion of the NB moiety from the CD cavity by guest accommodation. Using the guest-responsive fluorescence quenching properties of the CD-peptides, we have obtained binding constants for various short chain alkanols. -PL17 has higher binding affinity to the guest molecules than its isomer, -PR17, indicating that the location of functional groups on the peptide scaffold is important in molecule detection.     

The microenvironment in polymer solids with added plasticizers. An attempt to measure the size and distribution of free volume in poly(methyl methacrylate) solids

Various amounts of n-alkylbenzenes (C_n: C₆H₅-C_nH_2n+1 (n = 3-16)) were doped into poly(methyl methacrylate) (PMMA) films, and the emission and thermal properties of each film were measured in detail together with their solid-state ¹³C NMR spectra. The aim of the present work was to estimate the size distribution of free volume in amorphous regions of polymer solids heavily doped with plasticizers by using C_n as models of a plasticizer. The excimer fluorescence yields of C_n in PMMA were found to depend on both the amount of C_n and the length of the alkyl chains of C_n, although the fluorescence spectra of all of the C_ns in dilute fluid solution were almost the same. The quantitative analysis showed: (1) C_n with n ? 12 induces a phase separation in PMMA, in which almost all of the C_n molecules are in a separated phase, and thus they cannot penetrate regions in which PMMA chains are aggregated. This means that C_n with n ? 12 cannot enlarge the space between PMMA chains. (2) Smaller C_n (n < 11) can enter free volumes between PMMA chains that correspond to their molecular size, but they can enlarge them only to a limited extent. Thus, the amount by which plasticization can increase the free volume of PMMA is limited by the size of the dopant and the inherent free volume of the polymer matrix. (3) The efficiency of excimer formation was found to reveal the maximum amount of C_n that could fit in the free volume of PMMA. Thus our fluorescence measurements showed that PMMA solids that were plasticized to their limit had a free volume that was larger than the volume occupied by all the conformers of C₅ and smaller than the volume occupied by almost all the conformers of C₁₂. In conclusion, we were able to obtain information on plasticization and to demonstrate a method of monitoring microenvironments in polymer solids after they have been doped with plasticizers.     

Total Synthesis of Natural PI-091, a New Platelet Aggregation Inhibitor of Microbial Origin

The total synthesis of a new platelet aggregation-inhibiting gamma-lactam PI-091 (1) gave a 1:1 diastereomeric mixture at the gamma-ketal carbon. The high-yielding aldol reaction of an appropriately protected 1,3,4-trihydroxy-4-methyldecan-2-one 42, prepared from D-glucose, with the kinetically generated enolate of 3-methyl-2-butanone provided 43. The resulting diastereomeric mixture of the aldol adduct 43 was converted to a 2,4-alkylated furan 45 via an intramolecular ketalization followed by dehydration. The addition of a singlet oxygen to the alpha-trimethylsilylated furan 48derived from 45 under photochemical conditions efficiently provided an alpha,gamma-dialkylated gamma-hydroxy gamma-lactone 47. The transformation of methyl ketal 52 prepared from 47 into gamma-hydroxy gamma-lactam 53 was achieved by exposure to liquid ammonia in MeOH. The total synthesis of 1 was achieved from 52 through the Dess-Martin periodinane oxidation of the secondary hydroxy group in the side chain. The present total synthesis revealed that the stereogenic carbon center in the side chain in natural 1 is S.     

Pi-face-selective Diels-Alder reactions of 3,4-di-tert-butylthiophene 1-oxide and 1-imide and formation of 1,2-thiazetidines

3,4-Di-tert-butylthiophene 1-oxide (1a) reacted with a series of electron-deficient alkenic dienophiles at its syn-pi-face relating to the S=O bond to give [4+2] adducts in excellent yields. The 1-oxide 1a also reacted even with angle-strained dienophiles acenaphthylene and norbornene at its syn-pi-face to afford [4+2] adducts; in the latter case, norbornene reacted exclusively at its exo-pi-face. The oxide 1a reacted with dimethyl acetylenedicarboxylate to produce dimethyl 4,5-di-tert-butylphthalate in high yield with spontaneous extrusion of SO from the initial adduct even at room temperature. Similarly, 3,4-di-tert-butylthiophene 1-(p-toluenesulfonyl)imide (3a) reacted with alkenic dienophiles at its syn-pi-face relating to the S=N bond to give [4+2] adducts in good yields. The reaction of 3a with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) afforded a 1,2-thiazetidine 12a, the first example of S-unoxidized 1,2-thiazetidine, in good yield, through rearrangement of the initial [4+2] adduct. The molecular structure of 12a is discussed on the basis of the X-ray crystallographic analysis. Comparison of the foregoing reactions leads to the conclusion that the 1-oxide 1a is more reactive as a diene than the 1-imide 3a, which is more reactive than 3,4-di-tert-butylthiophene 1,1-dioxide. The origin of the syn-pi-face selectivities of 1a and 3a in Diels-Alder reactions is discussed in terms of the orbital mixing rule and steric effect and also based on B3LYP/6-31G(d) calculations.     

New chemosensor for larger guests based on modified cyclodextrin bearing seven hydrophobic chains each with a hydrophilic end group

A new chemosensor for larger guests was prepared. The new chemosensor bears hydrophobic units at the primary hydroxy side and a dansyl unit at the secondary hydroxy side of β-cyclodextrin. Due to the hydrophobic units, the new chemosensor is sensitive to large or slender guests such as SDS and insensitive to 1-adamantanol, which is a good guest for the natural β-CD.     

C-H to N substitution dramatically alters the sequence-specific DNA alkylation, cytotoxicity, and expression of human cancer cell lines

We designed and synthesized sequence-specific alkylating conjugates 1 and 2, which selectively alkylate matched sequences at nanomolar concentrations. Conjugates 1 and 2 differ only in that the C-H is substituted by an N in the second ring, which precisely recognizes and effectively alkylates DNA according to the recognition rule of Py-Im polyamides. We investigated sequence-specific DNA alkylation, cytotoxicity in 39 human cancer cell lines, and the effect on expression levels in cancer cell lines by Py-Im conjugates 1 and 2. The COMPARE analysis of the mean graphs showed that conjugates 1 and 2 did not correlate well with each other (r = 0.65) despite having a common DNA alkylating mechanism (purine N3 alkylation). Array-based gene expression analysis demonstrated that there are several oppositely regulated genes. The results suggest the intriguing possibility that DNA alkylating agents recognizing longer base-pair sequences may provide a promising approach for developing new types of antigene agents.     

Atomic one- and two-electron subshell moments in position and momentum spaces

For 357 subshells of the 53 neutral atoms He through Xe in their ground states, the two-electron intracule (relative motion) <u ^k > _nl and extracule (center-of-mass motion) <R ^k > _nl subshell moments in position space are examined as well as their counterparts <v ^k > _nl and <P ^k > _nl in momentum space, where n and l are the principal and azimuthal quantum numbers of the atomic subshell, respectively. It is clarified that between the intracule and extracule moments the “2 ^k -rule” is strictly valid, which means <u ^k > _nl = 2 ^k <R ^k > _nl and <v ^k > _nl = 2 ^k <P ^k > _nl for any nl subshell. Theoretical analysis also proves that for a particular case of k = +2, two relations <u ²> _nl = (N _nl −1)<r ²> _nl and <v ²> _nl = (N _nl −1)<p ²> _nl hold exactly, where N _nl (≥2) is the number of electrons in the subshell nl, and <r ^k > _nl and <p ^k > _nl are the familiar one-electron subshell moments in position and momentum spaces, respectively. The latter equality establishes a new and rigorous relation between the second electron-pair moments in momentum space and the total energy of an atom through the virial theorem. For k=+1, −1, and −2, the numerical Hartree-Fock results for the 357 subshells show that there are approximate but accurate linear relations between <u ^k > _nl and <r ^k > _nl and between <v ^k > _nl and <p ^k > _nl , in which the proportionality constant in each space depends on n,l, and k. Received: 27 April 1998 / Accepted: 29 May 1998 / Published online: 28 August 1998     

TYROSINE-SENSITIZED PHOTODIMERIZATION OF THYMINE IN AQUEOUS SOLUTION

Abstract. Photodimerization of thymine in aqueous solution in the presence of tyrosine was studied with monochromatic UV irradiation. The total dimer formation was sensitized in the presence of tyrosine. The action spectrum of sensitized total dimer formation has a peak near 280 nm corresponding to the absorption maximum of tyrosine. Triplet quenchers reduced the sensitization substantially. It seems probable that tyrosine-sensitized photodimerization of thymine occurred via triplet-triplet energy transfer from tyrosine to thymine.     

all-Z-Tetrabenzo

Crystal structures of the silver complexes derived from tetrabenzo[16]annulene with AgOTf and AgClO(4) are different, although these two complexes show similar (1)H NMR spectra reflecting a similar clathrate structure in solution. The silver complex of pentabenzo[20]annulene with AgClO(4) adopts a clathrate structure both in the solid state and in solution.