Chirality Emergence in Thin Solid Films of Amino Acids by Polarized Light from Synchrotron Radiation and Free Electron Laser

One of the most attractive hypothesis for the origin of homochirality in terrestrial bioorganic compounds is that a kind of “chiral impulse” as an asymmetric excitation source induced asymmetric reactions on the surfaces of such materials such as meteorites or interstellar dusts prior to the existence of terrestrial life (Cosmic Scenario). To experimentally introduce chiral structure into racemic films of amino acids (alanine, phenylalanine, isovaline, etc.), we irradiated them with linearly polarized light (LPL) from synchrotron radiation and circularly polarized light (CPL) from a free electron laser. After the irradiation, we evaluated optical anisotropy by measuring the circular dichroism (CD) spectra and verified that new Cotton peaks appeared at almost the same peak position as those of the corresponding non-racemic amino acid films. With LPL irradiation, two-dimensional anisotropic structure expressed as linear dichroism and/or linear birefringence was introduced into the racemic films. With CPL irradiation, the signs of the Cotton peaks exhibit symmetrical structure corresponding to the direction of CPL rotation. This indicates that some kinds of chiral structure were introduced into the racemic film. The CD spectra after CPL irradiation suggest the chiral structure should be derived from not only preferential photolysis but also from photolysis-induced molecular structural change. These results suggest that circularly polarized light sources in space could be associated with the origin of terrestrial homochirality; that is, they would be effective asymmetric exciting sources introducing chiral structures into bio-organic molecules or complex organic compounds

Sum frequency generation spectroscopy of the attachment disc of a spider

The pyriform silk of the attachment disc of a spider was studied using infrared-visible vibrational sum frequency generation (SFG) spectroscopy. The spider can attach dragline and radial lines to many kinds of substrates in nature (concrete, alloy, metal, glass, plant branches, leaves, etc.) with the attachment disc. The adhesion can bear the spider's own weight, and resist the wind on its orb web. From our SFG spectroscopy study, the NH group of arginine side chain and/or NH$_{2}$ group of arginine and glutamine side chain in the amino acid sequence of the attachment silk proteins are suggested to be oriented in the disc. It was inferred from the observed doublet SFG peaks at around 3300 cm$^{-1}$ that the oriented peptide contains two kinds of structures.Comment: 21 pages, 8 figure

DEUTERIUM AS A TOOL FOR CHANGING THE PROPERTIES OF PHARMACEUTICAL SUBSTANCES (REVIEW)

The review is devoted to the influence of the hydrogen isotope–deuterium on biological models of organisms and the biological activity of pharmaceutical substances. The positions of the influence of deuterium on the properties of active pharmaceutical ingredients and excipients are examined from different perspectives. The first position reflects an increase in the kinetic isotope effect (KIE) in processes involving known pharmaceutical substances in aqueous solutions with a deuterium/protium ratio (D/H) below natural. For the first time, the dose-response diagram shows the identity of deuterium with essential trace elements, when a deficiency and excess of an element reduces the organism's vitality. Improved kinetic characteristics are demonstrated for the molecular and organism levels of different hierarchical gradations. In particular, they consist in the possibility of increasing the dissolution rate of substances by influencing the carbohydrate mutarotation processes and the optical activity of chiral substances, increased accumulation of essential elements in medicinal plants and other processes associated with a possible change in metabolic pathways in the cell and the organism as a whole. The second considered position of the influence of deuterium is associated with the use of deuterated substances–new compounds or obtained by substitution of protium in known protium analogues. The KIE is presented, which is expressed in a decrease in the biotransformation rate as a result of deuteration, it allows predicting a rapid development of the new direction in the development of drugs. Having an identical therapeutic effect, deuterated analogs provide improved pharmacokinetic characteristics, such as reduced toxicity, blocked epimerization of optically active substances, and a change in the mechanisms of biotransformation. The obtained results make it possible to predict the mechanisms of the effect of deuterium on the biochemical transformations of pharmaceutical substances in the organism

Fundamental Investigations and Analysis of Chiral Matter Using Simple Spectroscopic Techniques

Fundamental investigations of circular dichroism were performed on (R)-(+)-3- methylcyclopentanone, (R)-(-)-2-butylamine, and (S)-(+)-2-butylamine in the liquid and vapor phase to show that solvents often have a structure-masking effect on the circular dichroism for a given molecule. Also, the solid state circular dichroism of cubic sodium chlorate crystals was successfully measured in the midst of adverse experimental circumstances. With these single photon circular dichroism studies at hand, a new technique for measuring circular dichroism was introduced for an advanced investigation of (R)-(+)-3-methylcyclopentanone. The resonance enhanced multiphoton ionization of (R)-(+)-3-methylcyclopentanone was performed with left and right circularly polarized laser light at a wavelength of 397.5 nm. This technique gave a dissymmetric factor g of 4.1 ± 0.23 x 10-2 in favor of the left circularly polarized light. Parity violating energy difference studies were conducted on the enantiomers of alanine and valine. The conversion of one enantiomer to the other at 273 K was found not to occur due to temperature dependent studies of circular dichroism, x-ray diffraction, C-13 solid state NMR, Raman spectroscopy, magnetic susceptibility, differential scanning calorimetry, and theoretical calculations. Highly intense 1064 nm pulsed laser light was used to induce crystallization in sodium chlorate, sodium bromate, and glycine aqueous solutions. The symmetry of sodium chlorate crystals and the asymmetry of sodium bromate crystals were broken by right circularly polarized and linearly polarized light, respectively. The g-polymorph of glycine was produced by an acidic pH change induced by the intense laser light. Under a Sr-90 source, 1,1’-binaphthyl crystallized into crystals showing a slight enantiomeric excess

Studies in chemotherapy

1. Outline of the nature of the published papers: The papers presented in the field of chemotherapy fall into two groups: (a) Papers on antimalarials; (b) Papers on antibiotic peptides and amino acids.In addition, the candidate presents, along with and as part of this thesis, his book, "The Basis of Chemotherapy", as an original contribution to the theoretical development of the subject.2. List of papers published on chemotherapy: || 1. King, H. and Work, T.;-. Antiplasmodial action and chemical constitution. Part III. Carbinolamines derived from naphthalene and quinoline. J.chem.Soc., 1940, p.1307. || 2. Work T.S. intiplasmodial action and chemical constitution. Part IV. The synthesis of some complex carbinolamines and polyamines. J.chem.Soc., 1940, p.1315. || 3. King, H. and Work T.S. Antiplasmodial action and chemical constituion. Part V. Carbinolamines derived from 6- methoxyquinoline. J.chem.Soc., 1942, p.401. || 4. Wore. T.S. Antiplasmodial action and chemical constitution. Part VI. Compounds related to lepidylamine. J.chem.Soc., 19112, p.426. || 5. Work. T.S. The synthesis of amines from amides through amidodichlorid.es. J.chem.Soc., 1942, p.429. || 6. Work, T.S. Antiplasmodial action and chemical constitution. Part VII. Derivatives of quinine and isoquinine. J. chem.Soc. , 1944 p. 334. || 7. Work, T.S. The synthesis of antimalarial compounds related to niquidine. Part I. Model experiments on the synthesis of r+.uinolyl carbinols. J. them. Soc. , 1946, p.194. || 8. Work, T.S. The synthesis of antimalarial compounds related to niquidine. Part II. Synthesis of a dihydro -x- niquidine. J. them. Toc. , 1946 p,197. || 9. Work, T.S. The synthesis of antimalarial compounds related to niquidine. Part III. Alternative synthesis of dihydro -x- niquidine. J.chem. Soc., 1947, p.222. || 10. Tonkin, I.M. and Work, T.S. A new antimalarial drug. Nature, 1945, 156, 630. || 11. Work, T.S. d- and 1- amino acids in antibiotics. Biochem.Soc.Symposia, 194.8, No. 1, p.61. || 12. Harris, J.I. and Work, T.S. Synthetic pentapeptides related to gramicidin -S. Nature, 1948, 161, 804. || 13. Harris, J.I. and Work, T.S. Lysine analogues as inhibitors of bacterial growth. Biochem.J., 1950, 46, 190. || 14- Harris, J.I. and Work, T.S. The synthesis of peptides related to gramicidin-S and the antibiotic peptides. I. Tri-peptides. Biochem.J., 1950, 46, 196. || 15. Harris, J.I. and Work, T.S. The synthesis of peptides related to gramicidin-S and the significance of optical configuration in antibiotic peptides. II. Penta-peptides. Biochem.J., 1950, 46, 582. || 16. Jerk, T.S. A discussion on antibiotic acitivity of growth factor analogues. Proc.Roy.Soc. , B, 1949, 136, 159. || 17. Work, T.S. and Work, P. The Basis of Chemotherapy. Oliver & Boyd, Edinburgh, 1948, xx, 4.35 p.3. Other original work presented. with this thesis: Since 1936, when the candidate was awarded the degree of Ph.D.) he has worked also in the field of natural product chemistry and has published original work on vitamin E, Cannabis indica resin, analogues of acetyl choline, the toxic factors in bleached wheat flour, and on local anaesthetics.4. List of papers relating to 3: || 18. Todd, A.R., Bergel, F., Taldmann, H. and 'ork, T.S. Constituents of vitamin E concentrates from rice- and wheat -germ oils. Nature, 1937, 1,,D, 361. || 19. Todd, A.R., Bergel, F., ';Taldmann, H. and '': fork, T.S. Studies on vitamin E. I. The isolation of some crystalline alcohols from the unsaponifiable matter of rice -and wheat -germ oils. Biochem.J. ,' 1937, 31, 2247. || 20. Todd, A.R., Bergel, F. and Work, T.S. Studies on vitamin II. The isolation of ß- tocopherol from wheat -germ oil. Biochem.J., 1937, 31, 2257. || 21. Bergel, F. , Jacob, A., ,Todd, A.R., and 'Work, T.S. Vitamin E Structure of 3- tocopherol. Nature, 1938, 14..1, 646. || 22. Bergel, F. , Todd, A.R. and ''Fork, T.S. Studies on vitamin E. Part III. Observations on the structure of a- and 3- tocopherol. J.chem. Soc., 1938, p.253. || 23. Bergel, F., Jacob, A. , Todd, A.R. and work, T.S. Vitamin E synthesis of a- tocopherol. Nature, 1938, 11.2, 36. || 24. Bergel, P. , Jacob, A., Todd, A.R. and 'Work, T.S. Studies on vitamin E. Part IV. Synthetic experiments in the couroaran and chroman series. The structure of the tocopherols. J. chem.Soc. , 1938, p. 1375. || 25. Bergel, F., Copping, 'i.l; . , Jacob, A., Todd., A.R. and Bork, T.S. Studies on vitamin Part V. Synthesis of racemic a- tocopherol and of a lower homologue. J. chem. S oc. , 1938, p.1382. || 26. Jacob, , Steiger, M., Todd, A.R. and 'pork, T.S. Studies on vitamin E. Part DTI. Synthesis of lower homologues of u- tocopherol. J.chem.Soc., 1939, p.542. || 27. Work, T.S., Bergel, F. and Todd, A.A. The active principles of Cannabis ind.ica resin. I. Biochem.J. , 1939, 33, 123. || 28. dark, T.S. The synthesis of N- trimethylglycycholine. J . chem. Soc. , 1941, p.190. || 29. Macintosh, F.C. and 7ork, T.S. Some aminoethanol derivatives possessing local anaesthetic acitivty. Quart.J.Fharmacy, 1914, lZ., 16. || 30. Work, T.S. The biochemical effects of mutation. Ann.Rep.Chemical Society, 1947, p.254- || 31. Campbell, P.N., Work, T.S. and Hellanby, Sir E. Isolation of a crystalline toxic factor from agenized -;heat flour. Rature, 1950, 165, 345. || 32. Campbell, P.L. , ffork, T.S. and Mellanby, Sir S. The isolation of a toxic substance from agenized wheat flour. Biochem, J., 1951, 48, 106

High pressure polymer science, routes to drug delivery

The area of high pressure is receiving great attention and being used to study a range of materials including metals, minerals, energetic materials and pharmaceuticals. Polymers are being increasingly used in pharmaceutical and biomedical applications. The main reason behind this is their physico-chemical characteristics that can be tuned to suit different applications. These characteristics can differ in different forms of the same compound. These forms can be obtained by different techniques including high pressure (Chapter 1).;The work presented in this thesis has used high pressure techniques, including diamond anvil cells (DACs) and large volume press cell, to investigate pharmaceutical polymers and a model active pharmaceutical ingredient (ibuprofen). The change of materials under pressure was studied by in-situ Raman spectroscopy (Chapter 2). The first challenge faced in this project was fluorescence, which hinders Raman spectroscopy.;Surface enhanced Raman spectroscopy (SERS) technique was adopted to improve the signal and overcome fluorescence. This was achieved successfully on weak Raman scattering amino acids and fluorescent polymers (Chapter 3). A range of commonly used polymers were studied under high pressure in DAC. Poly glycolic acid (PGA) and poly lactic acid (PLA) exhibited a similar phenomenon of moving from crystalline or semi-crystalline into a less ordered form between 4-5 GPa. Ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) demonstrated a similar change at about 2-3 GPa (Chapter 4).;Both EC and HPMC were used as a platform for sustained release dosage forms in different ratios with ibuprofen. These formulations were mixed using resonant acoustic mixing technique and subjected to high pressure (0.8 GPa) before being tested for drug release. The change in release patterns was mainly caused by the pressure transmitting medium (PTM) rather than the application of pressure (Chapter 5). Individual formulation components were used as received powders, treated by PTM at ambient pressure and subjected to 0.8 GPa before exploring their flowability.;The PTM treatment and pressure has increased the flow function of polymers but not ibuprofen. The formulation blends were tested for flowability in powder and ambient pressure forms. Unlike individual components, the treated blends exhibited a decrease in flow function and increase in cohesion (Chapter 6).;Overall, this thesis demonstrates that the application of pressure, using DACs, on commonly used polymers in pharmaceutical applications does help in inducing phase transitions at different pressures. Adapting SERS technique has been successful in overcoming fluorescence in polymers and improving Raman signal in weakly scattering amino acids. The application of pressure, using large volume press, did not have a significant effect on release pattern of APIs from the tested formulations.;The change was mainly due to the pressure transmitting medium. The effect of pressure was tested on powder flowability and found to increase polymers flowability but not ibuprofen.The area of high pressure is receiving great attention and being used to study a range of materials including metals, minerals, energetic materials and pharmaceuticals. Polymers are being increasingly used in pharmaceutical and biomedical applications. The main reason behind this is their physico-chemical characteristics that can be tuned to suit different applications. These characteristics can differ in different forms of the same compound. These forms can be obtained by different techniques including high pressure (Chapter 1).;The work presented in this thesis has used high pressure techniques, including diamond anvil cells (DACs) and large volume press cell, to investigate pharmaceutical polymers and a model active pharmaceutical ingredient (ibuprofen). The change of materials under pressure was studied by in-situ Raman spectroscopy (Chapter 2). The first challenge faced in this project was fluorescence, which hinders Raman spectroscopy.;Surface enhanced Raman spectroscopy (SERS) technique was adopted to improve the signal and overcome fluorescence. This was achieved successfully on weak Raman scattering amino acids and fluorescent polymers (Chapter 3). A range of commonly used polymers were studied under high pressure in DAC. Poly glycolic acid (PGA) and poly lactic acid (PLA) exhibited a similar phenomenon of moving from crystalline or semi-crystalline into a less ordered form between 4-5 GPa. Ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) demonstrated a similar change at about 2-3 GPa (Chapter 4).;Both EC and HPMC were used as a platform for sustained release dosage forms in different ratios with ibuprofen. These formulations were mixed using resonant acoustic mixing technique and subjected to high pressure (0.8 GPa) before being tested for drug release. The change in release patterns was mainly caused by the pressure transmitting medium (PTM) rather than the application of pressure (Chapter 5). Individual formulation components were used as received powders, treated by PTM at ambient pressure and subjected to 0.8 GPa before exploring their flowability.;The PTM treatment and pressure has increased the flow function of polymers but not ibuprofen. The formulation blends were tested for flowability in powder and ambient pressure forms. Unlike individual components, the treated blends exhibited a decrease in flow function and increase in cohesion (Chapter 6).;Overall, this thesis demonstrates that the application of pressure, using DACs, on commonly used polymers in pharmaceutical applications does help in inducing phase transitions at different pressures. Adapting SERS technique has been successful in overcoming fluorescence in polymers and improving Raman signal in weakly scattering amino acids. The application of pressure, using large volume press, did not have a significant effect on release pattern of APIs from the tested formulations.;The change was mainly due to the pressure transmitting medium. The effect of pressure was tested on powder flowability and found to increase polymers flowability but not ibuprofen

Growth and Characterization of some amino acid doped nlo materials crystals

The recent advances in science and technology have brought a great demand of various crystals with numerous applications. A field of multidisciplinary nature in science and technology has been emerged, known as crystal growth, which deals with the crysta