The quantitation of carbamino adduct formation of angiotensin II and bradykinin.

The two equilibrium constants that define the extent of carbamino adduct formation with amines for all values of pH and PCO2 are determined for the alpha-amino groups of the peptide hormones angiotensin II(AII) and bradykinin (BK) by nuclear magnetic resonance techniques. From these constants the variation of carbamino adduct formation has been calculated over the pH range 6.60--8.00 with variable PCO2, and the results are superimposed upon standard pH-bicarbonate diagrams. PCO2, and the results are superimposed upon standard pH-bicarbonate diagrams. The mole fraction, Z, of carbamino adduct form of AII or BK shows a maximum variation in going from metabolic alkalosis, Z congruent to 0.30, to metabolic acidosis, Z congruent to 0.02, with Z near 0.2 for normal acid-base conditions. Adduct formation to hormone may alter the biological effect of the hormone (a) by limiting proteolysis, particularly at the amino-terminal, (b) by altering hormone binding affinity to specific receptors, or (c) by converting the hormone to an antagonist which binds to receptor but does not activate subsequent metabolic events. The requirements for any of these mechanisms to operate are examined in terms of simple equilibrium considerations, and experimental evidence of inhibition of an aminopeptidase model system is presented. These results are consistent with the hypothesis that regulation of some physiological processes through formation of carbamino adduct of peptide hormones is possible

Solid-state deuterium NMR, iron-57 Moessbauer, and x-ray structural characteristics of .mu.3-oxo-bridged mixed-valence [Fe3O(O2CCH3)6(4-Me-py)3](C6H6): dynamics of the benzene solvate molecules influencing intramolecular electron transfer

Intramolecular electron transfer is investigated in the mixed-valence complex [Fe30(02CCH3)6(4-Me-py)3] (C6H6), where 4-Me-py is 4-methylpyridine. Rotational motion of the benzene solvate molecule and the possible influence of this motion on the rate of intramolecular electron transfer are studied crystallographically and spectroscopically. The compound crystallizes in the rhombohedral space group R32; a = b = 18.552 (3) A, c = 10.556 (2) A at 133 K with 2 = 3. The final discrepancy factors are R = 0.048 and R, = 0.061 for 1209 reflections with I > 340. Complex molecules and disordered benzene solvate molecules are stacked in alternate sites of 32 symmetry along the 3-fold c axis. The unit cell contains three such stacks related by a 31 axis. The 4-Me-py ligands are nearly coplanar with the Fe30 moiety. The 3l axis passes through the three nearly parallel 4-Me-py ligands of three adjacent stacks. The interligand separation, c/3 = 3.51 A, along the 3, axes probably controls the size of the solvate cavity along the 3-fold axis. Electron density maps indicate a preferred orientation for the benzene solvate molecule with its 6-fold axis perpendicular to both the crystallographic 3-fold and 2-fold axes. The large thermal parameter observed for the solvate molecule is consistent with a dynamic disorder of this group. Two doublets of area ratio 2:l (Fe"':Fe") are present in the MGssbauer spectrum at temperatures approaching liquid helium. As the sample temperature is increased above -60 K, the spectrum changes to eventually become a single average-valence doublet at temperatures above -200 K. The complex [Fe,0(02CCH3),(4-Me-py)3](Ci6nD w6h)i,ch perdeuteriobenzene is the solvate molecule, gives high-resolution ZH NMR spectra. Spectra are readily obtained from three sample types: random powders, magnetically oriented microcrystals, and single crystals. The spectral properties are determined both by the motionally averaged ZH quadrupolar coupling and by dipolar interactions of the deuterons with the unpaired electrons of the neighboring trinuclear complexes. These two types of interactions are readily separated in the ZH NMR experiment. Single-crystal 2H NMR data were obtained at room temperature by rotating a -1 X 1 X 1 mm crystal about three mutually orthogonal axes. Temperature studies were also carried out for powdered and magnetically oriented microcrystalline samples in the range of - 150-293 K. From the orientation and magnitude of the residual 2H quadrupolar coupling, it was concluded that the benzene solvate molecules are not only ring rotating about their c6 axes, but they are also rotating about the C3 stacking axes. An appreciable through-space dipolar interaction of the magnetic dipole of the deuterons with the magnetic dipoles of the nearby paramagnetic Fe30 complexes is present.We are grateful for support from National Institutes of Health Grant HL13652 (D.N.H.) and from National Science Foundation Grants PCM-8118912 (R.J.W.) and CHE-8340836 (C.E.S.)

Micromodulation: induction of intramolecular electron transfer by solvate molecule dynamics in the iron acetato oxo methylpyridine mixed-valence complex [Fe3O(O2CCH3)6(3-Me-py)3](solvate)

The oxo-centered, trinuclear, mixed-valence iron acetate complexes [Fe30(02CCH3)6(3-Me-py)w3h]e.reS S, = CH,CN (I), toluene (Z), 3-methylpyridine (3), and benzene (4), have been prepared, and the intramolecular electron transfer properties in the solid state have been studied. It is found that the rate of electron transfer is dramatically influenced by changing the solvate molecule. The complex 1 crystallizes in the monoclinic space group P2,/c with 4 molecules in a unit cell which has dimensions a = 12.760 ( 5 ) A, b = 26.233 (1 1) A, c = 14.819 ( 5 ) A, and /3 = 116.20 (3)'. Compound 2 crystallizes in the triclinic space group Pi with 2 = 2, a = 13.056 (4) A, b = 15.902 (3) A, c = 12.896 (2) A, a = 102.82 (2)O, /3 = 118.96 (Z)', and y = 70.02 (2)'. The complex 3, isostructural with 2, was characterized in the triclinic space group Al with Z = 4: at 128 K, a = 12.964 ( 5 ) A, b = 12.976 (4) A, c = 29.293 (9) A, a = 84.01 ( 1 ) O , /3 = 94.41 (l)', and y = 121.76 (1)'; at 298 K, a = 13.114 (4) A, 6 = 13.052 (4) A, c = 30.054 ( 5 ) A, a = 85.81 (4)', /3 = 95.23 (4)', and y = 120.99 ( 5 ) ' . The complex 1 has valence-trapped electronic states from 120 to 298 K on the Mossbauer time scale, and non-equivalent metal sites are seen in its single-crystal X-ray structure. The other three complexes are isostructural as indicated by the single-crystal X-ray structures of 2 and 3 and by a comparison of room-temperature powder X-ray diffraction patterns determined for all three complexes. The three complexes 2, 3, and 4 also exhibit similar Mossbauer spectra. At temperatures below - 100 K there are two doublets in the area ratio of two (high-spin Fell') to one (high-spin Fe"). Increasing the sample temperature of 2, 3, and 4 above - 100 K leads to the appearance of a third average-valence doublet with a small spectral area. Eventually the spectrum changes upon increasing the temperature to become a single-average doublet. The X-ray structural work for 3 carried out at 298 and 128 K shows that the dimensions of the Fe30 triangular complex change appreciably with temperature. The Fe, triangle of 3 at 128 K is asymmetric with three inequivalent Fe ions; the triangle becomes more equilateral at the higher temperature. The solid-state packing arrangement of 2, 3, and presumably 4 consists of Fe30 units arranged twodimensionally in layers with the solvate molecule located in an open space made by three neighboring Fe30 molecules. In the case of 1 CH3CN molecules are sandwiched between pairs of Fe30 molecules. The Fe30 complexes in 2 and 3 adopt a symmetric conformation with all three 3-methylpyridine ligands approximately perpendicular to the Fe30 plane, while in 1 two of the 3-methylpyridine ligands are parallel to the Fe30 plane. The effects of conformation on the charge distribution and intramolecular electron-transfer rate are discussed in light of these and previously reported results. Intramolecular electron transfer is slow in 1 because the environment about the Fe30 complexes in 1 leads to an asymmetric complex with inequivalent iron ions. This inequivalence introduces appreciable potential-energy barriers for intramolecular electron transfer. In the case of 2,3, and 4 it is suggested that an order-disorder phase transition involving motion of the solvate molecules influences the rate of intramolecular electron transfer. A single-crystal 2H NMR study of 2 with perdeuterated toluene shows that at 293 K the toluene solvate molecules are involved in two motions. There is a twofold ring flip about the para axis, and the toluene solvate molecule is jumping between two lattice positions. Variable-temperature (290 to 140 K) 2H NMR data are presented for a microcrystalline sample of 2 with perdeuterated toluene to show that, while the solvate molecule motion has not completely stopped by 140 K, the motion has slowed down considerably.We are grateful for support from National Institutes of Health Grants HL13652 (D.N.H.) and GM35329 (C.E.S.) and from National Science Foundation Grants PCM- 81 18912 (R.J.W.) and CHE-8340836 (C.E.S.)