Spectrophotometric Determination of Gold in Biological Materials
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University of Windsor Scholarship at UWindsor Electronic Theses and Dissertations Theses, Dissertations, and Major Papers 1-1-1969 Spectrophotometric determination of gold in biological materials. Robert J. Walton University of Windsor Follow this and additional works at: https://scholar.uwindsor.ca/etd Recommended Citation Walton, Robert J., "Spectrophotometric determination of gold in biological materials." (1969). Electronic Theses and Dissertations. 6075. https://scholar.uwindsor.ca/etd/6075 This online database contains the full-text of PhD dissertations and Masters’ theses of University of Windsor students from 1954 forward. These documents are made available for personal study and research purposes only, in accordance with the Canadian Copyright Act and the Creative Commons license—CC BY-NC-ND (Attribution, Non-Commercial, No Derivative Works). Under this license, works must always be attributed to the copyright holder (original author), cannot be used for any commercial purposes, and may not be altered. Any other use would require the permission of the copyright holder. Students may inquire about withdrawing their dissertation and/or thesis from this database. For additional inquiries, please contact the repository administrator via email ([email protected]) or by telephone at 519-253-3000ext. 3208. SPECTROPHOTOMETRIC DETERMINATION OP GOLD IN BIOLOGICAL MATERIALS BY ROBERT J. WALTON A Dissertation Submitted to the Faculty of Graduate Studies through the Department of Chemistry in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy at the University of Windsor Windsor, Ontario 1969 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number: DC52642 INFORMATION TO USERS The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. UMI® UMI Microform DC52642 Copyright 2008 by ProQuest LLC. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 E. Eisenhower Parkway PO Box 1346 Ann Arbor, Ml 48106-1346 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. V ' £ Approved ^ -T *£>^p (EXTERNAL EXAMINER) 248577 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ABSTRACT A spectrophotometric method for the determination of low levels of gold(III) with di-2-pyrldylketoxime was developed. A stable 2 j1 water-soluble complex is formed having an absorption maximum at ^33 nm and a molar absorptivity of Ij, 1.89 x 10 . The Beer-Lambert law is obeyed up to 12 ppm. The method was applied to the determination of gold in plasma and urine. The method is simple, reproducible and relatively rapid. li Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACKNOWLEDGEMENTS The author wishes to thank Dr, R.J. Thibert for his assistance in the design and direction of this research project. The author also wishes to thank Drs. W.J. Holland, John Bozic and Jesse Gerard for their interest and advice. Finally,the author wishes to gratefully acknowledge the financial assistance from the Government of the Province of Ontario in the form of Ontario Graduate Fellowships. iii Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. TABLE OF CONTENTS Page ABSTRACT............ ii ACKNOWLEDGEMENTS.............................. iii TABLE OF CONTENTS................................ iv LIST OF FIGURES............................ Vl LIST OF TABLES ........................ vii Chapter I. INTRODUCTION........... 1 II. EXPERIMENTAL A. MATERIALS AND METHODS Apparatus .*.. .. 11 Reagents ...................... 11 Procedure. .............. 13 Computer Programs. .......... 15 B. RESULTS Studies with HAuCl^. 31^0............. 16 Preliminary Studies................... 18 Gold Determination in Plasma and Urine................................. 20 III. DISCUSSION............................... 33 IV. SUMMARY.............. 37 APPENDIX I ......... 38 APPENDIX II....................................... *fl iv Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. REFERENCES... VITA AUCTORIS Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. LIST OP FIGURES Figure Page 1 ABSORPTION SPECTRA OF GOLD(III) COMPLEX AND REAGENT BLANK........................... 22 2 EFFECT OF REAGENT CONCENTRATION..... 26 3 CONTINUOUS VARIATION AND MOLAR RATIO STUDIES......................... 28 vi Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. LIST OF TABLES Table Page I DATA FOB RINGBOM PLOT.. ................ 23 II EFFECT OF pH ON ABSORBANCE.............. 2b III REPRODUCIBILITY DATA................ 29 IV EFFECT OF DIVERSE IONS.................. 30 V EFFECT OF COPPER (II).................... 31 VI RECOVERY OF KNOWN AMOUNTS OF GOLD ADDED TO PLASMA AND URINE............... 32 vii Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. CHAPTER I INTRODUCTION Gold and its derivatives have been used in medicine throughout written history to treat every conceivable dis order. The beginning of a rational chemotherapy with gold came with Koch's demonstration (1) in 1890 that potassium auricyanide inhibited the growth of the tubercle bacillus in vitro at a concentration of 1 in 2 million. White (2) in 189^ showed that sodium aurichloride had some antibacterial effect in tuberculosis but was toxic. In 1913» several reports appeared to the effect that « simple gold compounds such as potassium auricyanide showed therapeutic activity in cases of tuberculosis and syphilis. This was sufficient to encourage attempts to develop better tolerated derivatives such as that of Spiess and Peldt (3). They introduced what was considered to be a less toxic com plex of aurous cyanide, 'Aurocantan* (cantharidylethylenedi- amine aurocyanide), but this compound caused necrosis after repeated subcutaneous administration and its use was limited. The outstanding feature of the chemistry of gold is the 'nobility' of the element, that is, the difficulty with which it can be made to participate in chemical reactions and form firm chemical bonds with other elements. Furthermore such compounds are relatively unstable and often revert under 1 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. mild conditions to the elemental form. Both Au(I) and Au(III) show an extremely marked tenden cy to form complexes and in so-called gold salts of ionic character in aqueous solution, the ions always involve gold complexed with other elements. A certain lack of understanding of the precise nature of complex gold derivatives has led to some confusion in past work on the mode of action of these substances and some misconceptions of the structural formulae of those compounds which have been put to clinical use. Both Au(I) and Au(III) compounds exist among such substances. It is worth noting that the coordination number in Au(I) compounds is almost always two and that there is a strong affinity for sulfur, little for nitrogen and carbon and none for oxygen; while the more stable and numerous Au(III) compounds are always four-coordinate and there is a marked affinity for oxygen and halogen, some affinity for nitrogen and none for sulfur. These considerations lie behind the development of particu lar water-soluble derivatives of gold for chemotherapeutic use, through the selection of suitably ionized complexing systems. The frequency with which gold-sulfur complexes have appeared among chemotherapeutic gold derivatives supported the idea that their activity owed more to the sulfur content than the gold. This was successfully disposed of by Preston, Block and Preyberg (*J-). Spiess and Peldt (5) developed 'Krysolgan* (2-auro-thio- Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 4-aminobenzoic acid) in which the gold(I) was linked to an organic molecule through a firm sulfur bond. Other workers supported Feldt*s claim that 'Krysolgan' was as active as sodium auricyanide against Mycobacterium tuberculosis but could not confirm his view that it was much less toxic. The next decade saw the introduction of a number of other gold-sulfur complexes as tuberculostats and antisyph ilitic agents. Feldt, undaunted by the severe toxic effects of these gold compounds, pursued his study of aromatic auro- thio derivatives and there appeared successively 'from the Farbwerke Hoechst laboratories the water-soluble products *Solganal* (3-aurothio-*t— sulfophenylaminomethanesulfonate), introduced to clinical practice about 192?, and the hetero cyclic aurothio compound 'Triphal* (sodium 2-auro^thiobenz- imidazole-4-carboxylate). These compounds were administered intravenously. In the meantime, the compound sodium aurothiosulfate which Feldt had shown in 1913 to have antibacterial activity