Showing papers by "Peter G. Schultz published in 1982"

Design synthesis of a sequence-specific DNA cleaving molecule. (Distamycin-EDTA)iron(II)

Abstract: The sequence-dependent recognition of nucleic acids by proteins and small molecules is important in the regulation of many biological processes. A large class of these molecules are bifunctional in nature, combining a chemically reactive moiety with a DNA binding unit. One such molecule is the naturally occurring antitumor antibiotic bleomycin, which binds to and cleaves DNA sequence specifically in a reaction that depends on Fe(II) and oxygen. Recently we reported the synthesis of a DNA binding-DNA cleaving molecule, methidiumpropyl-EDTA (MPE). This bifunctional molecule has the DNA intercalator, methidium, tethered to a metal chelator, EDTA. MPE·Fe(II) cleaves double helical DNA in the presence of dithiothreitol (DTT) with efficiencies comparable to those of bleomycin·Fe(Il)/DTT. Unlike bleomycin·Fe(II), MPE·Fe(II) cleaves DNA non-sequence-specifically, consistent with solution studies demonstrating that the intercalator methidium has no overall base composition specificity.

Direct studies of 1,1-diazenes. Syntheses, infrared and electronic spectra, and kinetics of the thermal decomposition of N-(2,2,6,6-tetramethylpiperidyl)nitrene and N-(2,2,5,5-tetramethylpyrrolidyl)nitrene

Abstract: The syntheses, direct spectroscopic observation, and kinetics of thermal decomposition of the persistent 1,1-diazenes, N-(2,2,6,6-tetramethylpiperidyl)nitrene (4) and N-(2,2,5,5-tetramethylpyrrolidyl)nitrene (5) are reported. The electronic absorption spectrum of 4 at -78 °C reveals a structured absorption for the n,π* transition: λmax= 543 nm, λ_(0,0) = 620 nm, and emax = 18 ± 3 in Et_2O; λmax= 541 nm and λ_(0,0) = 610 nm in CH_2Cl_2; λmax= 526 nm and λ_(0,0) = 592 nm in i-PrOH. The infrared spectrum of 4 shows a strong absorption at 1595 cm^(-1)(R_2^(14) = ^(14)N stretch) and provides evidence that 1,1-diazene 4 has considerable N=N double-bond character in the ground state. The infrared spectrum of 5 shows a strong absorption at 1638 cm^(-1)(R_2^(14) = ^(14)N stretch). The unimolecular rate of thermal decomposition of 4 is sensitive to solvent, the rate increasing with decreasing solvent polarity (k_(re1) = 1.0, 1.7, 4.8 in THF, Et_2O, and hexane, respectively). The activation parameters for the unimolecular fragmentation of 1,1-diazene 4 are as follows: log A = 11.6 • 0.5 and E_a= 16.9 ± 0.7 kcal mo1^(-1) in hexane; log A = 13.7 ± 0.3 and E_a = 20.0 ± 0.4 kcal mo1^(-1) in Et_2O; log A = 13.6 ± 0.3 and E_a = 20.l ± 0.4 kcal mol^(-1) in THF. The activation parameters for the bimolecular dimerization of 4 are log A = 3.8 ± 0.7 and E_a = 6.4 ± 0.9 kcal mol^(-1) in CDC1_3. The unimolecular rate of thermal decomposition of 5 is sensitive to solvent, the rate increasing with decreasing solvent polarity, k_(rel) = 1.0, 2.4, and 5.1 for THF, Et_2O, and hexane, respectively. The activation parameters for the unimolecular fragmentation of 1,1-diazene 5 are as follows: log A = 10.9 ± 0.3 and E_a = 16.8 ± 0.5 kcal mo1^(-1) in hexane; log A = 12.4 ± 0.4 and E_a = 19.0 ± 0.6 kcal mo1^(-1) in Et_2O; log A= 12.1 ± 0.3 and E_a = 19.l ± 0.4 kcal mo1^(-1) in THF. At -41.1 °C the bimolecular rate constant for the dimerization of 5 is 8.5 X 10^(-5) L/(mol s), 90 times slower than that found for 4. The change from a six-membered to a five-membered ring 1,1-diazene causes a shift to higher energy for the n,π'* transition and a shift to increased wavenumber (cm^(-1)) for the N=N stretching frequency, not unlike that of the isoelectronic ketones, tetramethylcyclohexanone and tetramethylcyclopentanone. Similar E_a values for the unimolecular thermal fragmentation of 4 and 5 may indicate the strain energy difference between 4 and 5 is also small. An approximate value of 30.5 kcal mo1^(-1) for the heat of formation of the 1,1-diazene 5 is estimated, indicating the 1,1-diazene 5 has a higher heat of formation than the cis-1,2-diazene isomer by 20 kcal mo1^(-1).

Photochemistry of 1,1-diazenes. Direct and sensitized photolyses of N-(2,2,5,5-tetramethylpyrrolidyl)nitrene, dl-N-(2,5-diethyl-2,5-dimethylpyrrolidyl)nitrene, and N-(2,2,6,6-tetramethylpiperidyl)nitrene

Abstract: The photochemistry of the l, 1-diazenes N-(2,2,5,5-tetramethylpyrrolidyl)nitrene (1), d/-N-(2,5-diethyl-2,5-dimethylpyrrolidyl) nitrene (2), and N-(2,2,6,6-tetramethylpiperidyl)nitrene (3) is reported. The fluorescence spectrum of 1,1-diazene 1 has a 0-0 band at 607 nm, which is the maximum. The spacing between the peaks at 607 and 672 nm corresponds to the N=N stretch of S0 consistent with the 1638-cm^(-1) stretch obtained from the infrared spectrum of 1. The fluorescence quantum yields are Φ_F = 2 X 10^(-3) (MTHF, -78 °C), 7 x 10^(-3) (MTHF, -196 °C), and l X 10^(-3) (EPA, -196 °C). The fluorescence lifetime of 1 is T_F = 2.3 x 10^(-8) s (CFCl_3, -196 °C). Direct irradiation of 1 (466-610 nm, -78 °C) affords four hydrocarbon products, 54% 4, 44% 5, 2% 6 + 7 and tetrazene 8. Triplet-sensitized photodecomposition afforded 74% 4, 24% 5, 2% 6 + 7 and tetrazene 8. An approximate quantum yield for decomposition on direct irradiation is Φ_D = 1.1 x 10^(-2). From S_1, kN_2 is >3.4 X 10^5 s^(-1), and reaction of S_0 with S_1. k_(DIM) is >4.2 x 10^7 L mo1^(-1) s^(-1) (at -78 °C). The spectrum of 1,1-diazene 2 reveals a structured absorption with λmax 507 nm and a 0-0 band at 568 nm (e = 20). The vibrational spacing is 1270 cm^(-1). The fluorescence spectrum of 1,1-diazene 2 has a 0-0 band at 620 nm, which is the maximum. The spacing between the maxima at 620 and 690 nm corresponds to the N=N stretch of S_0 consistent with the 1630-cm^(-1) stretch obtained for the infrared spectrum of 2. The fluorescence quantum yield Φ_F = 9 X 10^(-3) (MTHF, -196 °C). The direct and sensitized irradiation of 2 in the visible affords hydrocarbon products 14-19 and tetrazene 20 in different ratios. The retention of stereochemistry in the cyclobutane products in the direct and sensitized photodecomposition was 98 and 68%, respectively, similar to the spin correlation effect seen in corresponding 1,2-diazene isomer. This indicates that for 2 (and by extension 1) k_(isc) << k_(N2), consistent with a large S_1-T_1 gap in 1,1-diazenes. For 1,1-diazene 3 the fluorescence spectrum has a single maximum at 684 nm. The fluorescence quantum yield Φ_F = 4 X 10^(-4) (MTHF, -196 °C). The estimated fluorescence lifetime is T_F = 4 X 10^(-9)s. Direct irradiation of 3 in the visible at -78 °C afforded three hydrocarbon products, 29% 21, 3% 22, 68% 23 and tetrazene 25.

Photochemistry of 1,1-diazenes. Direct and sensitized photolyses of N-(2,2,5,5-tetramethylpyrrolidyl)nitrene, dl-N-(2,5-diethyl-2,5-dimethylpyrrolidyl)nitrene, and N-(2,2,6,6-tetramethylpiperidyl)nitrene

Abstract: The photochemistry of the l, 1-diazenes N-(2,2,5,5-tetramethylpyrrolidyl)nitrene (1), d/-N-(2,5-diethyl-2,5-dimethylpyrrolidyl) nitrene (2), and N-(2,2,6,6-tetramethylpiperidyl)nitrene (3) is reported. The fluorescence spectrum of 1,1-diazene 1 has a 0-0 band at 607 nm, which is the maximum. The spacing between the peaks at 607 and 672 nm corresponds to the N=N stretch of S0 consistent with the 1638-cm^(-1) stretch obtained from the infrared spectrum of 1. The fluorescence quantum yields are Φ_F = 2 X 10^(-3) (MTHF, -78 °C), 7 x 10^(-3) (MTHF, -196 °C), and l X 10^(-3) (EPA, -196 °C). The fluorescence lifetime of 1 is T_F = 2.3 x 10^(-8) s (CFCl_3, -196 °C). Direct irradiation of 1 (466-610 nm, -78 °C) affords four hydrocarbon products, 54% 4, 44% 5, 2% 6 + 7 and tetrazene 8. Triplet-sensitized photodecomposition afforded 74% 4, 24% 5, 2% 6 + 7 and tetrazene 8. An approximate quantum yield for decomposition on direct irradiation is Φ_D = 1.1 x 10^(-2). From S_1, kN_2 is >3.4 X 10^5 s^(-1), and reaction of S_0 with S_1. k_(DIM) is >4.2 x 10^7 L mo1^(-1) s^(-1) (at -78 °C). The spectrum of 1,1-diazene 2 reveals a structured absorption with λmax 507 nm and a 0-0 band at 568 nm (e = 20). The vibrational spacing is 1270 cm^(-1). The fluorescence spectrum of 1,1-diazene 2 has a 0-0 band at 620 nm, which is the maximum. The spacing between the maxima at 620 and 690 nm corresponds to the N=N stretch of S_0 consistent with the 1630-cm^(-1) stretch obtained for the infrared spectrum of 2. The fluorescence quantum yield Φ_F = 9 X 10^(-3) (MTHF, -196 °C). The direct and sensitized irradiation of 2 in the visible affords hydrocarbon products 14-19 and tetrazene 20 in different ratios. The retention of stereochemistry in the cyclobutane products in the direct and sensitized photodecomposition was 98 and 68%, respectively, similar to the spin correlation effect seen in corresponding 1,2-diazene isomer. This indicates that for 2 (and by extension 1) k_(isc) << k_(N2), consistent with a large S_1-T_1 gap in 1,1-diazenes. For 1,1-diazene 3 the fluorescence spectrum has a single maximum at 684 nm. The fluorescence quantum yield Φ_F = 4 X 10^(-4) (MTHF, -196 °C). The estimated fluorescence lifetime is T_F = 4 X 10^(-9)s. Direct irradiation of 3 in the visible at -78 °C afforded three hydrocarbon products, 29% 21, 3% 22, 68% 23 and tetrazene 25.