Organic solvents for bioorganic synthesis

Summary The influence of solvents on enzymatic activity and stability was investigated. As a model reaction the -chymotrypsin-catalyzed esterification of N-acetyl-l-phenylalanine with ethanol was used. The enzyme was adsorbed on porous glass beads and used in various solvents. Small amounts of water were added to increase the enzymatic activity. These enzyme preparations obeyed. Michaelis-Menten kinetics. K _m,app decreased slightly with the log P value of the solvent while V _app increased markedly with the log P value. Log P values were also useful for generalizing the influence of solvents on enzyme stability. The enzyme preparations showed a markedly higher thermostability in dry solvents having log P values >0.7 than in less hydrophobic solvents.Also the operational stability was better in the more hydrophobic solvents. The amount of water added to the enzyme preparations greatly influenced the initial reaction rates. For some solvents optimal water contents were determined. The thermostability decreased with increasing water content.The observations are summarized in the conclusion that more hydrophobic solvents are preferable to less hydrophobic ones. The log P value gives a good guidance when selecting an organic solvent for enzymatic conversions.     

Organic synthesis by quench reactions

The effects of chemical quench reactions on the formation of organic compounds at a water surface under simulated primordial earth conditions were investigated for the study of chemical evolution. A mixture of gaseous methane and ammonia over a water surface was exposed to an arc discharge between an electrode and the water surface. This discharge served as a source of dissociated, ionized and excited atomic and molecular species. Various organic molecules were formed in the gaseous, aqueous, and solid states by a subsequent quenching of these reactive species on the water surface. The effects of these water-surface quench reactions were assessed by comparing the amounts of synthesized molecules to the amounts which formed during the discharge of an arc above the water level. The results showed that: (1) the water-surface quench reaction permitted faster rates of formation of an insoluble solid and (2) the quench discharge yielded twice as much amino acids and 17 times more insoluble solids by weight than the other discharge. The highest yield of amino acids with the quench reaction was 9×10⁷ molecules per erg of input energy. These observations indicate that quench reactions on the oceans, rain, and clouds that would have followed excitation by lightning and shock waves may have played an important role in the prebiotic milieu. Furthermore, the possibility exists that quench reactions can be exploited for the synthesis of organic compounds on a larger scale from simple startng materials.     

Organic synthesis by quench reactions.

The effects of chemical quench reactions on the formation of organic compounds at a water surface under simulated primordial earth conditions were investigated for the study of chemical evolution. A mixture of gaseous methane and ammonia over a water surface was exposed to an arc discharge between an electrode and the water surface. This discharge served as a source of dissociated, ionized and excited atomic and molecular species. Various organic molecules were formed in the gaseous, aqueous, and solid states by a subsequent quenching of these reactive species on the water surface. The effects of these water-surface quench reactions were assessed by comparing the amounts of synthesized molecules to the amounts which formed during the discharge of an arc above the water level. The results showed that: (1) the water-surface quench reaction permitted faster rates of formation of an insoluble solid and (2) the quench discharge yielded twice as much amino acids and 17 times more insoluble solids by weight than the other discharge. The highest yield of amino acids with the quench reaction was 9 x 10-7 molecules per erg of input energy. These observations indicate that quench reactions on the oceans, rain, and clouds that would have followed excitation by lightning and shock waves may have played an important role in the prebiotic milieu. Furthermore, the possibility exists that quench reactions can be exploited for the synthesis of organic compounds on a larger scale from simple starting materials.     

Organic Acid specificity for Acid-induced ATP synthesis by isolated chloroplasts

A study has been made of the structural requirements for organic acids that increase the yield of ATP formed by spinach chloroplasts in the dark due to an acid-base transition. Dicarboxylic acids of 4 and 5 carbon atoms with 1 pKa in the range of 4.2 to 4.4 and the second at 5.3 to 5.5 are most effective. A fairly good correlation was found between the fraction of the acid completely undissociated at the test pH and the final yield. Other considerations are also important, however, since introducing hydroxyl groups or excessive chain length decreased yields in spite of pKa considerations. Aromatic acids, except for the dicarboxylic phthalic acids, were inhibitory. The diversity of organic acids having some effect makes it unlikely that they serve as substrate for a chloroplast enzyme system.     

Organic synthesis in algal cells separated into age groups by fractional centrifugation

Summary Synthesis of organic matter was studied in cells of the green, high-temperature alga Chlorella 7-11-05 separated from a nonsynchronized population into fractions of predominantly small or large cells by centrifugation. Rates of synthetic activity were determined as changes in optical density, dry weight, and packed volume of cells in several suspending fluids and under various light intensity conditions.It was found that synthetic activity of the smaller (younger) cell fraction was invariably higher than that of the larger (older) cell fraction, provided a reasonably good separation of cells into size fractions was achieved during centrifugation and the difference between size composition of these fractions was maintained throughout observation.An occasional lack of difference in the performance of the small- and large-cell fractions, or even a higher synthetic activity of the originally large-cell fraction, was traced to cell division taking place during observation. Under conditions favorable to cell division, the large-cell fraction was progressively enriched with smaller (younger) cells, the average age composition of the originally large-cell fraction was shifted toward younger age, and the metabolic activity of the large-cell fraction increased to the extent that, in some experiments, it surpassed that of the originally small-cell fraction.The decline in synthetic activity of cells in the course of cell development previously observed on synchronized cells was thus substantiated on nonsynchronized populations in the absence of the light: dark synchronizing agent and is, therefore, characteristic of normal cell development.     

Organic synthesis using polymer-supported reagents,catalysts and scavengers in simple laboratory flow systems

The use of appropriate combinations of polymer-supported reagents, catalysts and/or scavengers is a powerful approach, both for the synthesis of single organic compounds and for parallel syntheses. A further stage of development is the use of such reactants in flow systems. So far, it has been shown that a variety of flow formats afford excellent chemical yields and, where relevant, excellent enantiomeric excesses. The supports have a longer lifetime than in batch systems. 'Flow cascades' promise to be important in future.     

Organic hydroperoxides at high concentrations cause energization and activation of ATP synthesis in mitochondria

The addition of high concentrations of cumene or tert-butyl hydroperoxide to previously deenergized mitochondria results in the energization of these mitochondria and activation of ATP synthesis. The energization effect was observed in the presence of 0.5-0.7 mM cumene hydroperoxide or 2.0-2.5 mM tert-butyl hydroperoxide. This energization of mitochondria and activation of oxidative phosphorylation by organic hydroperoxides required the presence of ADP in the mitochondrial matrix and does not depend upon the method of deenergization of the mitochondria.     

Organic synthesis in pursuit of immunology: large-scale synthesis of peracetylated GM2 glycosylamino acid for preparation of a multiantigenic prostate cancer vaccine

We describe herein the stereo-controlled, large-scale synthesis of peracetylated GM2 glycosylamino acid. Key features of the synthesis include a newly modified [1+3] coupling reaction and an olefin cross-metathesis-hydrogenation sequence. The GM2 glycosylamino acid is now ready for incorporation into a hexavalent prostate cancer vaccine construct.