A dilute solution of water in a hydrophobic solvent, such as carbon tetrachloride (CCl4), presents an opportunity to study the rotational properties of water without the complicating effects of hydrogen bonds. We report here the results of theoretical, experimental, and semiempirical studies of a 0.03 mole percent solution of water in CCl4. It is shown that for this solution there are negligible water-water interactions or water-CCl4 interactions; theoretical and experimental values for proton NMR chemical shifts (deltaH) are used to confirm the minimal interactions between water and the CCl4. Calculated ab initio values and semiempirical values for oxygen-17 and deuterium quadrupole coupling constants (chi) of water/CCl4 clusters are reported. Experimental values for the 17O, 2H, and 1H NMR spin-lattice relaxation times, T1, of 0.03 mole percent water in dilute CCl4 solution at 291 K are 94+/-3 ms, 7.0+/-0.2 s, and 12.6+/-0.4 s, respectively. These T1 values for bulk water are also referenced. "Experimental" values for the quadrupole coupling constants and relaxation times are used to obtain accurate, experimental values for the rotational correlation times for two orthogonal vectors in the water molecule. The average correlation time, tauc, for the position vector of 17O (orthogonal to the plane of the molecule) in monomer water, H2(17)O, is 91 fs. The average value for the deuterium correlation time for the deuterium vector in 2H2O is 104 fs; this vector is along the OD bond. These values indicate that the motion of monomer water in CCl4 is anisotropic. At 291 K, the oxygen rotational correlation time in bulk 2H2(17)O is 2.4 ps, the deuterium rotational correlation time in the same molecule is 3.25 ps. (Ropp, J.; Lawrence, C.; Farrar, T. C.; Skinner, J. L. J. Am. Chem. Soc. 2001, 123, 8047.) These values are a factor of about 20 longer than the tauc value for dilute monomer water in CCl4.
Considerable efforts have been made to develop technologies for selection of peptidic molecules that act as substrates or binders to a protein of interest. Here we demonstrate the combination of rational peptide array library design, parallel screening and stepwise evolution, to discover novel peptide hotspots. These hotspots can be systematically evolved to create high-affinity, high-specificity binding peptides to a protein target in a reproducible and digitally controlled process. The method can be applied to synthesize both linear and cyclic peptides, as well as peptides composed of natural and non-natural amino acid analogs, thereby enabling screens in a much diverse chemical space. We apply this method to stepwise evolve peptide binders to streptavidin, a protein studied for over two decades and report novel peptides that mimic key interactions of biotin to streptavidin.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Nitrosamines are well-known for their toxic and carcinogenic properties. The metabolic activation of nitrosamines occurs via interaction with the heme-containing cytochrome P450 enzymes. We report the preparation and structural characterization of a number of nitrosamine adducts of synthetic iron porphyrins. The reactions of the cations [(por)Fe(THF)2]ClO4 (por = TPP, TTP, OEP) with dialkylnitrosamines (R2NNO; R2 = Me2, Et2, (cyclo-CH2)4, (cyclo-CH2)5, (PhCH2)2) in toluene generate the six-coordinate high-spin (S = 5/2) [(por)Fe(ONNR2)2]ClO4 compounds and a five-coordinate intermediate-spin (S = 3/2) [(OEP)Fe(ONNMe2)]ClO4 derivative in 57−72% yields (TPP = 5,10,15,20-tetraphenylporphyrinato dianion, TTP = 5,10,15,20-tetra-p-tolylporphyrinato dianion, OEP = 2,3,7,8,12,13,17,18-octaethylporphyrinato dianion). The N−O and N−N vibrations of the coordinated nitrosamine groups in [(por)Fe(ONNR2)2]ClO4 occur in the 1239−1271 cm−1 range. Three of the six-coordinate [(por)Fe(ONNR2)2]ClO4 compounds and one five-coordinate [(OEP)Fe(ONNMe2)]ClO4 compound have been characterized by single crystal X-ray crystallography. All the nitrosamine ligands in these complexes bind to the ferric centers via a sole η1-O binding mode. No arylnitrosamine adducts were obtained from the reactions of the precursor compounds [(por)Fe(THF)2]ClO4 with three arylnitrosamines (Ph2NNO, Ph(Me)NNO, Ph(Et)NNO). However, prolonged exposure of [(por)Fe(THF)2]ClO4 to these arylnitrosamines resulted in the formation of the known five-coordinate (por)Fe(NO) derivatives. The latter (por)Fe(NO) compounds were obtained more readily by the reactions of the three arylnitrosamines with the four-coordinate (por)FeII precursors.
Abstract Hydroxylamine (NH 2 OH) is an important molecule in biology that serves as an intermediate in the nitrogen cycle, and that can also be utilized as a nitric oxide donor in mammals under certain conditions. In light of this, the interaction of NH 2 OH with hemes in proteins and model systems has gained much attention recently. In this study, we use the more stable, oxygen substituted O‐benzylhydroxylamine (NH 2 OBn) as a model for NH 2 OH. Here, the reactivity of the ferric bis‐picket fence porphyrin complexes [Fe(3, 5‐Me‐BAFP)(ClO 4 )] ( 1 ) and [Fe(3, 5‐Me‐BAFP)(PF 6 )] ( 2 ) (3,5‐Me‐BAFP 2– = dianion of tetra(2, 6‐bis(3,5‐dimethylphenoxy)phenyl)porphyrin)) with NH 2 OBn is investigated. The product of these reactions is characterized by UV/Vis and EPR spectroscopy and X‐ray crystallography. We found that addition of excess NH 2 OBn to our ferric porphyrin complexes results in reduction of the heme to the ferrous oxidation state. This is followed by disproportionation of additional NH 2 OBn to yield the ferrous complex [Fe(3,5‐Me‐BAFP)(NH 3 ) 2 ] ( 3 ) as the final product. The crystal structure of ( 3 ) constitutes the first structural characterization of a bis‐ammonia complex of a ferrous heme. The stability of this complex may be facilitated by the picket fences of the porphyrin ligand used here.
This Communication addresses a long-standing problem: the exact vibrational assignments of the low-energy modes of the Fe−N−O subunit in six-coordinate ferrous heme nitrosyl model complexes. This problem is addressed using nuclear resonance vibrational spectroscopy (NRVS) coupled to 15N18O isotope labeling and detailed simulations of the obtained data. Two isotope-sensitive features are identified at 437 and 563 cm−1. Normal coordinate analysis shows that the 437 cm−1 mode corresponds to the Fe−NO stretch, whereas the 563 cm−1 band is identified with the Fe−N−O bend. The relative NRVS intensities of these features determine the degree of vibrational mixing between the stretch and the bend. The implications of these results are discussed with respect to the trans effect of imidazole on the bound NO. In addition, a comparison to myoglobin-NO (Mb-NO) is made to determine the effect of the Mb active site pocket on the bound NO.
