Parity violation and the evolution of biomolecular homochirality.

Parity violation at the level of terrestrial biopolymers, as seen in proteins, DNAs, and RNAs, and parity violation at the level of nuclear processes, as evident in longitudinally polarized beta-particles and parity-violating energy differences (PVEDs), are discussed and their fundamental importances are emphasized. Attempts to find a causal connection between the unique homochirality of biopolymers and parity violation at the nuclear level, and speculations that the former is a consequence of the latter, are reviewed. Consideration of all lines of evidence leads to the conclusion that there is no substantiation for such a causal connection, and that the two levels of parity violation are entirely independent of each other.

Asymmetric photolysis with elliptically polarized light.

Previous investigations have shown the efficacy of right-(RCPL) and left-(LCPL) circularly polarized light in promoting the asymmetric photolysis of racemic organic substrates and producing measurable enantiomeric excesses (e.e.s) when photolysis is incomplete. Synchrotron radiation, polychromatic and having out-of-plane components which are elliptically and ultimately circularly polarized, has been suggested as a universal source of RCPL and LCPL on a cosmic scale. The more prevalent right-(REPL) and left-(LEPL) elliptically polarized components have never been investigated for similar capabilities. The present study, using a 212.8 nm laser beam to mimic the synchtrotron radiation, explores the potential of REPL and LEPL in this context and finds a qualitative trend indicating that each induces asymmetric photolysis in the same sense as RCPL and LCPL, but to a lesser degree.

Enantioselective autocatalysis. V. The spontaneous resolution of tri-o-thymotide.

We have attempted to appraise experimentally the allegation that minute chemical and physical differences due to the parity violating energy difference (PVED) between enantiomers are, after suitable autocatalytic amplification, ultimately responsible for the homochirality of contemporary biomolecules. The autocatalytic amplification technique employed involved the spontaneous resolution under racemizing conditions (SRURC) of a conglomerate during crystallization, and the system studied was the known crystallization of P(+)- or M(-)-tri-o-thymotide (TOT) as its optically active inclusion compound (clathrate) with benzene. Our premise was that if a PVED effect were operative, there should be a strong and consistent bias favoring the crystallization of one enantiomer of the TOT-benzene clathrate. Repetitive preparations of the clathrate, however, yielded crystalline products showing random optical activity. These results thus afford no evidence whatsoever for stereoselective bias due to a PVED, and are in accord with earlier statistical studies demonstrating random SRURC in other conglomerate crystallizations, again indicating the inefficacy of PVEDs to promote a preferred chirality in such systems.

Extraterrestrial handedness: a reply.

Recent investigations of stable isotope ratios of amino acids from the Murchison meteorite have shown them to be of unambiguous extraterrestrial origin, and examinations of their enantiomeric compositions, where terrestrial contamination can be excluded, have found a consistent excess of L-enantiomers. One explanation for this observation has been the asymmetric photolysis of racemic extraterrestrial amino acids by circularly polarized light (CPL) in the synchrotron radiation from orbiting electrons around the pulsar remnants of supernovae. Mason (1997) has attempted to discredit this mechanism on the grounds that circular dichroism (CD) bands for optically active molecules alternate in sign and sum to zero over the entire spectrum, and hence enantioselective photochemical reactions cannot be induced by broad band CPL. We submit arguments disputing this conclusion and present reasons for expecting that broad band CPL synchrotron radiation would be quite capable of inducing asymmetric photolysis, particularly in aliphatic amino acids.

The extraterrestrial origin of the homochirality of biomolecules--rebuttal to a critique.

Having concluded that abiotic terrestrial mechanisms would have been ineffectual for the origin of terrestrial homochirality, we have proposed an alternative extraterrestrial scenario involving stereoselective ultraviolet photolysis of the racemic constituents of interstellar grain mantles by circularly polarized synchrotron radiation from neutron stars, followed by terrestrial accretion of the resulting chiral molecules via cometary impact. Recently L. Keszthelyi (1995) has reviewed a number of our arguments and advanced several erroneous calculations and conclusions purporting to negate them. We offer here points of rebuttal to Keszthelyi's criticisms, and support our inferences with recent data regarding indigenous enantiomeric excesses of L-amino acids in the Murchison meteorite.

The radiolysis and radioracemization of poly-L-leucines.

The brief history of the discovery of radioracemization, the racemization of an optically active substance induced by ionizing radiation, is reviewed. Our early studies involving the radiolysis and radioracemization of D- and L-leucine using gamma radiation from a 111-TBq 60Co gamma-ray source are described briefly, as are later experiments involving other protein amino acids and their salts, as well as the nonprotein amino acid, isovaline. The implications of the results of such studies for the Vester-Ulbricht mechanism which proposes longitudinally polarized beta radiation as the origin of molecular chirality, for the cosmological question of the enantiomeric compositions of amino acids in the Murchison meteorite, and for the use of D/L ratios of amino acids for geochronological and geothermal estimates are reviewed briefly. These past radiolysis-radio- racemization studies have involved only monomeric amino acids. The present research, extending such investigations to two homochiral L-leucine polypeptides, (L-Leu)10 and (L-Leu)78, was undertaken to see if a polymer of an amino acid might be more stable to radiolysis and radioracemization than the corresponding monomer. It was found that these polypeptides were more stable to radiolysis than was the leucine monomer, but that the extents of radioracemization in all samples were comparable.

Chirality amplification--the accumulation principle revisited.

The chirality amplification mechanism proposed by Yamagata in 1966, relying on an Accumulation Principle which involved the parity violating energy difference (1 + epsilon) presumed to be operative at each step in the formation of a homochiral biopolymer, is briefly surveyed historically. The Accumulation Principle is then examined analytically and found to be incapable of producing a unique homochiral polymer in any realistic polymerization process. The extension of the Accumulation Principle to crystallizations which afford enantiomorphic crystals is also scrutinized and found to be misapplied and invalid.

Homochirality and life.

After clarifying the frequently misused term homochirality, the crucial importance of homochirality and chiral purity in the development and maintenance of the essential biopolymers of life--proteins and nucleic acids--is discussed. The harsh and forbidding prebiotic environment during the era of cometary impact after formation of the Earth approximately 4.5 Gyr ago is described, after which the most important abiotic mechanisms proposed historically for the genesis of chiral molecules on the primitive Earth are enumerated. Random and determinate terrestrial mechanisms are each evaluated with regard to the environmental restraints imposed during the impact era, and it is concluded that all such mechanisms would be inapplicable and implausible in the realistic prebiotic environment. To circumvent these limitations, an extended hypothesis is presented describing an extraterrestrial source of homochiral terrestrial molecules. Illustrated in Figure 2, this scenario involves the partial asymmetric photolysis of the racemic constituents of organic mantles on interstellar dust grains by the circularly polarized ultraviolet components of the synchrotron radiation emanating from the neutron star remnants of super-novae. The resulting homochiral constituents with low enanantiomeric excesses (e.e.s) so produced in the organic mantles are subsequently conveyed to Earth either by direct accumulation or, more likely, after coalescence into comets or asteroids, followed by repetitive impingement during the impact era. Finally, the low e.e.s of the extraterrestrial homochiral molecules so introduced are amplified by terrestrial autocatalytic or polymerization mechanisms into a state of chiral purity, then are ultimately concentrated and protected by sequestration in the interiors of spontaneously formed protocellular vesicles--there to await further chemical evolution toward the biomolecules of life. Recent observations of the excess of L-over D-amino acids in the Murchison meteorite are cited as validation for the early stages of the proposed hypothesis.

Enantioselective autocatalysis. IV. Implications for parity violation effects.

Historically, parity violation at the contemporary biomolecular level (i.e., only L-amino acids in proteins and D-sugars in DNA and RNA) has been postulated to be the inevitable result of parity violations at the elementary particle level, involving either beta-decay electrons or parity violating energy differences (PVEDs) between enantiomers. These two chiral biases have in turn allegedly impressed a small but persistent chirality onto prebiotic chemistry which, after appropriate amplification, has culminated in our contemporary homochiral biopolymers. Experiments and controversies pertaining to the efficacy of these two chiral biases are reviewed briefly, with the conclusions that: a) there is no experimental evidence supporting the capability of beta-decay electrons or other spin-polarized chiral particles to generate chiral molecules, and b) only theoretical calculations, but no experimental evidence, support the allegation of a causal relation between PVEDs and biomolecular homochirality. We here attempt to examine the latter allegation experimentally. Spontaneous resolution under racemization conditions (SRURC) during the crystallization of the bromofluoro-1,4-benzodiazepinooxazole derivative I is capable of affording products of high enantiomeric purity. This process, which involves very efficient stereoselective autocatalysis, has now been examined statistically. If PVED effects are operative, the SRURC of racemic I should provide, either exclusively or with a strong and consistent bias, only one enantiomer of crystalline I. However, crystallization experiments of racemic I showed no bias in its SRURC, leading to the conclusion that PVED effects are ineffective in dictating a preferred chirality in this system. Several earlier experiments in the literature leading to a similar conclusion as to the inefficacy of PVED effects in promoting a preferred chirality are noted.

Enantioselective autocatalysis. III. Configurational and conformational studies on a 1,4-benzodiazepinooxazole derivative.

We report here on configurational and conformational studies undertaken on the bromofluoro-1,4-benzodiazepinooxazole derivative I, which has previously been found capable of undergoing total spontaneous resolution under racemizing conditions. Due to its bridgehead N-atom I may exist in any of four diastereomeric forms, CRNR (or CSNS) and CRNS (or CSNR). Molecular mechanics calculations revealed that in their lowest energy conformations the CRNR (or CSNS) diastereomers were favored over the CRNS (or CSNR) diastereomers by some 3.42 kcal/mol, while semi-empirical quantum mechanical calculations indicated heats of formation also favoring the CRNR (or CSNS) diastereomers by 3.83 kcal/mol. The 1H NMR spectra of the three crystalline modifications (alpha, beta and gamma) of I were examined in acetone, and found to be identical. These data, combined with the results of the above calculations, suggest that I exists in methanol or methanol-acetone solutions as the CRNR (or CSNS) enantiomer prior to its racemization.

Enantioselective autocatalysis. II. Racemization studies on a 1,4-benzodiazepinooxazole derivative.

Since the bromofluoro-1,4-benzodiazepinooxazole derivative I may undergo spontaneous resolution on crystallization from methanol solution, it provides an ideal substrate on which to study the phenomenon of enantioselective autocatalysis involving spontaneous resolution under racemizing conditions (SRURC). In order to augment the understanding of factors which might be important in such a process we have now undertaken to study the racemization of I in more detail by observing its rate under a wide variety of experimental conditions.

Chirality and life.

The crucial role of homochirality and chiral homogeneity in the self-replication of contemporary biopolymers is emphasized, and the experimentally demonstrated advantages of these chirality attributes in simpler polymeric systems are summarized. The implausibility of life without chirality and hence of a biogenic scenario for the origin of chiral molecules is stressed, and chance and determinate abiotic mechanisms for the origin of chirality are reviewed briefly in the context of their potential viability on the primitive Earth. It is concluded that all such mechanisms would be nonviable, and that the turbulent prebiotic environment would require an ongoing extraterrestrial source for the accumulation of chiral molecules on the primitive Earth. A scenario is described wherein the circularly polarized ultraviolet synchrotron radiation from the neutron star remnants of supernovae engenders asymmetric photolysis of the racemic constituents in the organic mantles on interstellar dust grains, whereupon these chiral constituents are transported repetitively to the primitive Earth by direct accretion of the interstellar dust or through impacts of comets and asteroids.

Supernovae, neutron stars and biomolecular chirality.

Recent theoretical and experimental investigations of the origin of biomolecular chirality are reviewed briefly. Biotic and abiotic theories are evaluated critically with the conclusion that asymmetric photochemical processes with circulary polarized light (CPL), particularly asymmetric photolyses, constitute the most viable mechanisms. Solar CPL sources appear too weak and random to be effective. We suggest an alternative CPL source, namely, the synchrotron radiation from the neutron star remnants of supernova explosions. This could asymmetrically process racemic compounds in the organic mantles of the dust grains in interstellar clouds, and the resulting chiral molecules could be transferred to Earth by cold accretion as the solar system periodically traverses these interstellar clouds.

The radiolysis and radioracemization of amino acids on clays.

L-Leucine and its hydrochloride salt have been deposited on the clay minerals kaolin and bentonite, and the amino acid/clay preparations have been irradiated in a 3000 Ci60Co gamma-ray source for radiation dosages that achieved 2-89% radiolysis of the leucine. The undecomposed leucine was thereupon recovered and both percent radiolysis and percent radioracemization were determined. Similar studies were made using solid L-leucine and its hydrochloride, and L-leucine in 0.1 M aqueous solution. It has been found that radiolysis and radio-racemization in these and the previously studied leucine systems follow pseudo-first-order rate laws, and the corresponding specific rate constants are evaluated and compared. Leucine and its hydrochloride salt proved to be the most stable to both radiolysis and radioracemization, followed by leucine and its HCl salt on kaolin, followed by leucine and its HCl salt on bentonite, with leucine (and its HCl and Na salts) in aqueous solution being least stable to both radiolysis and (except for the HCl salt) radioracemization. Implications of these observations as regards the Vester-Ulbricht mechanism for the origin of optical activity are discussed.

Experimental evidence for beta-decay as a source of chirality by enantiomer analysis.

Earlier experiments testing the Vester-Ulbricht beta-decay hypothesis for the origin of molecular chirality are reviewed, followed by descriptions of our own experiments involving attempted asymmetric radiolysis of DL-amino acids using quantitative gas chromotography as a probe for optical activity. Our radiation sources included 90Sr-90Y, 14C and 32P Bremsstrahlen, longitudinally polarized electrons from a linear accelerator and longitudinally polarized protons from a cyclotron. With the possible exception of the linear accelerator irradiations, these experiments failed to produce g.c.-detectable enantiomeric excesses, even at 50-70% gross radiolysis. We thus find no unambiguous support for the Vester-Ulbricht hypothesis in any of the attempted asymmetric radiolyses performed to date. Radioracemization, a possible reason for these failures, is discussed.

Beta-decay, bremsstrahlen, and the origin of molecular chirality.

A brief review is presented of the Vester-Ulbricht beta-decay Bremsstrahlen hypothesis for the origin of optical activity, and of subsequent experiments designed to test it. Certain of our experiments along these lines, begun in 1974 and involving the irradiation of racemic and optically active amino acids in a 61.7 KCi 90Sr-90Y Bremsstrahlen source, have now been completed and are described. After 10.89 years of irradiation with a total Bremsstrahlen dose of 2.5 X 10(9) rads, crystalline DL-leucine, norleucine, and norvaline suffered 47.2, 33.6, and 27.4% radiolysis, respectively, but showed no evidence whatsoever of asymmetric degradation. D- and L-Leucine underwent about 48% radiolysis and showed 2.4-2.9% radioracemization. Other samples in solution were too severely degraded to analyze. Probable intrinsic reasons for the failure of the Vester-Ulbricht mechanism to afford asymmetric radiolysis in the present and related experiments involving beta-decay Bremsstrahlen are enumerated.

The radiolysis and racemization of leucine on proton irradiation.

D- and L-Leucine have been subjected to 39-55 percent radiolysis using 0-11 MeV protons, both with the proton beam passing through the sample or being absorbed by it, and with quenching the sample immediately on completion of irradiation or after a 21-day interval. Racemization was small (1.1-1.7 percent) and comparable in all cases, suggesting that radioracemization and secondary degradative effects were not important factors in our recent unsuccessful attempts to induce optical activity in DL-leucine by partial radiolysis using 0-11 MeV longitudinally polarized protons.

The radiolysis and radioracemization of amino acids on silica surfaces.

L-Leucine, deposited on both 1-quartz powder and on a commercial amorphous silica preparation (Syloid 63), has been subjected to irradiation in a 60Co gamma-ray source, and the ensuing radiolysis and radioracemization have been determined gas chromatographically. The radiolysis and radioracemization observed for leucine on 1-quartz were rather similar to those noted for a crystalline L-leucine control. L-Leucine on Syloid 63, however, was vastly more susceptible to radiolysis as compared to the L-leucine control, and radioracemization was also markedly enhanced - each increasing with larger radiation dosage. L-Isovaline showed a similar, but diminished, enhancement of radiolysis sensitivity when adsorbed on the Syloid surface, but underwent no radioracemization whatsoever. The divergent results of the control and quartz-leucine irradiations versus the Syloid-leucine and Syloid-isovaline irradiations are interpreted qualitatively in terms of the surface area parameters of the two silica adsorbents and the amino acid adsorbates.