Benjamin F. Plummer

Melatonin directly scavenges hydrogen peroxide: a potentially new metabolic pathway of melatonin biotransformation

A potential new metabolic pathway of melatonin biotransformation is described in this investigation. Melatonin was found to directly scavenge hydrogen peroxide (H(2)O(2)) to form N(1)-acetyl-N(2)-formyl-5-methoxykynuramine and, thereafter this compound could be enzymatically converted to N(1)-acetyl-5-methoxykynuramine by catalase. The structures of these kynuramines were identified using proton nuclear magnetic resonance, carbon nuclear magnetic resonance, and mass spectrometry. This is the first report to reveal a possible physiological association between melatonin, H(2)O(2), catalase, and kynuramines. Melatonin scavenges H(2)O(2) in a concentration-dependent manner. This reaction appears to exhibit two distinguishable phases. In the rapid reaction phase, the interaction between melatonin and H(2)O(2) reaches equilibrium rapidly (within 5 s). The rate constant for this phase was calculated to be 2.3 x 10(6) M(-1)s(-1). Thereafter, the relative equilibrium of melatonin and H(2)O(2) was sustained for roughly 1 h, at which time the content of H(2)O(2) decreased gradually over a several hour period, identified as the slow reaction phase. These observations suggest that melatonin, a ubiquitously distributed small nonenzymatic molecule, might serve to directly detoxify H(2)O(2) in living organisms. H(2)O(2) and melatonin are present in all subcellular compartments; thus, presumably, one important function of melatonin may be complementary in function to catalase and glutathione peroxidase in keeping intracellular H(2)O(2) concentrations at steady-state levels.

Photochemical heavy-atom effect. IV. External and internal heavy-atom effects upon the reaction of acenaphthylene with cyclopentadiene

The photochemical cycloaddition of acenaphthylene (la) and 5-bromoacenaphthylene (lb) to cyclopentadiene (2) produces the cycloadducts 3, 4, and 5. These reactions were studied in the solvents cyclohexane, acetonitrile, bromoethane, bromobenzene, 1,2-dibromoethane, and dibromomethane. The triplet nature of each reaction was confirmed by comparison of the product ratios obtained in various solvents in the Rose Bengal sensitized irradiations to the product ratios in the direct irradiations. Good Stern-Volmer relationships were obtained when the quencher ferrocene was used. The quantum yield of product formation has been shown to vary with the concentration of 2 in a manner consistent with a proposed triplet state mechanism. A comparison of the internal and external heavy-atom effect (HAE) upon the various dynamic processes occurring in the acenaphthylene system has been made. It is concluded that the rate processes involved in the radiationless mechanisms T1 t) S1 and TI +-+ So are affected by different degrees when the internal heavy-atom perturbation is compared to the external one. A method is devised to show that relative reactivities of the excited triplet states of la and l b are about the same. owan and Driskol first established that the photoC dimerization of acenaphthylene (la) was highly sensitive to perturbation by brominated solvents (external heavy atoms). While the effect of heavy atoms on photophysical processes has been thoroughly studied by spectroscopic techniques, known photochemical manifestations are limited. l f 3 r 4 The ability to enhance product yield or to change product ratios through the heavy-atom effect (HAE) intrigued us. Thus, we reported that acrylonitrile and its derivatives can be cross-cycloadded to l a by use of the HAE.6 This report stimulated others to use the HAE to crosscycloadd l a to maleic anhydride.6 The synthetic value of the HAE became apparent when the synthesis of pleiadiene was reduced to a four-step procedure involving the HAE.6a Because the requirements for a photochemical HAE remained enigmatic we undertook a detailed study of the photoreaction of l a with cyclopentadiene (2).’ Anticipating somewhat different results, we studied the photoaddition of 5bromoacenaphthylene ( l b ) t o 2.8 These results appeared in preliminary form and (1) (a) D. 0. Cowan and R. L. Drisko, Tetrahedron Lert. , 1255 (1967); (b) J . Amer. Chem. Soc., 89, 3068 (1967); (c) ibid., 92, 6281 (1970). (2) (a) G. A. Giachino and D. R. Kearns, J . Chem. Phys., 52, 2964 (1970); (b) S. K. Lower and M. A. El-Sayed, Chem. Reo., 66, 199 (1966); (c) M. A. El-Sayed, Accounts Chem. Res., 1, 8 (1968); (d) S. P. McGlynn, T. Azumi, and M. Kinoshita, “The Triplet State,” PrenticeHall, Englewood Cliffs, N. J., 1969. (3 ) We define a photochemical heavy-atom effect as a change in either quantum yield or product distribution when a given reaction perturbed by a heavy atom is compared to the similar reaction without heavy-atom perturbation. (4) The following papers have reported photochemical heavy-atom effects in compounds other than acenaphthylene. (a) S. P. Pappas and R. D. Zehr, Jr., J. Amer. Chem. Soc., 93, 7112 (1971); (b) R . Hoffman, P. Wells, and H. Morrison, J . Org. Chem., 36, 102 (1971); (c) G. Fischer, I<. A. Muszkat, and E. Fischer, Isr. J . Chem., 6 , 965 (1968); (d) F. Wilkinson and J. T. Dubois, J . Chem. Phys., 48,2651 (1968). (5) B. F. Plummer and R. A. Hall, Chem. Commun., 44 (1970). (6) (a) J. Meinwald, G. E. Samuelson, and M. Ikeda, J . Amer. Chem. SOC., 92, 7604 (1970); (b) J. E. Shields, D. Gavrilovic, and J. Kopecky, Tetrahedron Lett., 271 (1971); (c) W. Hartmann and H. G. Heine, Anaew. Chem.. In?. Ed. End. . 10.273 11971). (7) B. F. Plummer andD: M: Chihal, J: Amer. Chem. Soc., 93, 2071 (1971); 94, 6248 (1972). they are discussed in detail in this report with additional data that we have obtained.

Electron transfer properties of non-alternant, substituted compounds related to fluoranthene. Experimental determination and theoretical modeling of electrochemical oxidation and reduction potentials in non-aqueous solution

The oxidation and reduction potentials of a series of related even non-alternant derivatives of 7,14-disubstituted acenaphth[1,2-k] fluoranthenes, and also fluoranthene, 7,10-diphenylfluoranthene and 8,9-dihydrodiindeno[1,2-j;2′,1′-] fluoranthene, were determined in organic solvents by cyclic voltammetry. The effects of steric hindrance on conjugation of the substituents with the central polycyclic aromatic hydrocarbon nucleus were evaluated. The semi-empirical molecular orbital calculation programs OMEGAMO, Extended Huckel, AM1 and PM3 were used to obtain optimal geometries and calculated HOMO and LUMO energies. As a further refinement, COSMO solvation was included in the AM1 calculations. The redox properties were correlated with data derived from the various semi-empirical calculations and the quality of these correlations is discussed. Inclusion of solvation energies in the computed molecular orbital energies results in a significant improvement in the correlation between observed and calculated oxidation potentials.

The photodimerization of aceanthrylene

Abstract Sensitized photodimerization of aceanthrylene ( AA ) with Rose Bengal in methanol produced both syn and anti head-to-head and head-to-tail stereoisomers with slight preference for syn adducts. The stereochemical configurations were assigned by deuterium labeling and by high field homonuclear shift correlation (COSY) experiments and these compare favorably with the assignments made for the photodimers of 1-substituted acenaphthylenes. Currently, AA has photodimerized under direct irradiation only in carbon disulfide.

Polycyclic aromatic hydrocarbons with five-membered rings: Modeling of experimental X-ray and neutron-diffraction structures

Several of the readily available theoretical programs are evaluated as tools for modeling the structures of polycyclic aromatic hydrocarbons with five-membered rings (CPAHs). The experimentally determined bond lengths and angles are compared to calculated values. Experimental bond lengths are also compared to Pauling and Huckel molecular orbital (HMO) bond orders. Previously published experimental X-ray and neutron-diffraction structures of acenaphthene, acenaphthylene, fluoranthene, cyclopent[o,p,q,r]benz[c]phenanthrene, and corannulene are modeled by the programs MMX, AM1, MNDO, and PM3, and previously reported STO-3G and 6-31G * data are also evaluated. In general, the error differences between the experimental and calculated results for all of the semiempirical programs were small. However, PM3 performed slightly better than AM1 and MMX, while MNDO generated structures which exhibited the largest deviation from experiment. Although the standard deviations for all programs are shown to be of comparable magnitude, a particular bond length or bond angle in any given theoretical calculation can exhibit significant error from the experimental data. The scatter in the bond order data computed from Huckel molecular orbital theory and valence bond theory is contrary to results obtained with alternant systems. It appears that these approaches are less successful at modeling accurately the nonalternant hydrocarbon systems described in this paper.

The structure of 7,14-dicarbonylethoxyacenaphth[l,2-k]-fluoranthene and its tetracyanoquinodimethane charge transfer complex

A molecular mechanics simulation of the structure of 7,14-dicarbonylethoxyacenaphth[l,2-k]fluoranthene,1, indicated a preferred geometry for the hindered substituents in which the carbonyl groups were constrained to an anti conformation because of the steric hindrance associated with the in-plane buttressing hydrogen atoms. X-ray crystallographic analysis of1 verifies the correctness of the computation. Compound1 and tetracyanoquinodimethane,2, form a charge transfer complex, and a crystal structure analysis shows a slightly offset, nearly parallel arrangement of the acceptor with the π cloud of the donor. The interplanar distance of 3.45 Å between acceptor and donor lies within the statistical limits of the interplanar distance of π complexes formed between2 and a variety of PAH donors. The steric hindrance caused by the substituents in1 appears to offer only minimal interference to the formation of the π complex.

Modeling and NMR Studies of Somè Polycyclic Aromatic Hydrocarbons

Abstract The utility of molecular modeling in interpreting the 1H NMR spectra of selected polycyclic aromatic hydrocarbons that are deformed from their normal geometries is illustrated. The application of COSY and NOESY 1H NMR spectra in conjunction with the predicted geometries of these compounds is presented as an aid to the assignment of chemical shifts and spin spin coupling interactions. It is shown that chemical intuition about anisotropic shielding effects in magnetic resonance spectra must be used with caution. Computational modeling of the three dimensional structure of PAH is a useful tool for understanding the spectroscopic and chemical behavior of PAH.

Structure and Photochemistry of Cyclopentene Fused Polycyclic Aromatic Hydrocarbons

Abstract This review focuses on physico-chemical aspects of cyclopentene-fused polycyclic aromatic hydrocarbons (CPAH) that we are currently studying. Steric effects, deformation of polycyclic skeletons from planarity, radical ions, and excited states are properties being investigated. Molecular modeling as a tool for predicting the geometries of CPAH is discussed.

The synthesis and X-Ray crystallographic analysis of a stable norbornadienone: 17-Oxo-7,16-methano-7,16-diphenylcyclopenta[d,e]tribenzo[a,h,j]anthracene

The reaction of 4,5-didehydroacenaphthene with phencyclone yields the title compound, a stable dibenzo-fused norbornadienone (8). The X-ray structure of8 is presented and compared with the structure predicted from a MM3, PM3, and a MMX calculation. Thermal decomposition of 8 produces, 7,16-diphenylcyclopenta[d,e]tribenzo[a,h,j]anthracene (9), a hydrocarbon that is computed to have a significantly twisted polycyclic aromatic skeleton with 19 kcal/mole of strain energy.