A course in bioinorganic chemistry.
From time to time, it happens that new directions in chemistry at the research level develop a degree of coherence such that a new subdiscipline emerges. A name is coined; dedicated journals are launched; and specialized conferences are held. Soon, textbooks are written, and before long university departments must give serious thought to the introduction of a lecture course. Such has been the case with what is variously known as `inorganic biochemistry' or `bio-inorganic chemistry'.
Most likely, the task will befall one of the inorganic staff who is not himself, or herself, actually conducting a research programme in bioinorganic chemistry, since not all chemistry departments have research programmes in this area. This was certainly the case at Simon Fraser University. By describing the course we give, it is hoped to give encouragement and to provide a useful commentary for those, particularly non-specialists, planning to introduce a bioinorganic course into their curriculum.
We introduced our course in the mid-1970s. It is a one-semester 300 level course carrying three credits in the 120-credit majors degree programme. The course consists of three 50-minute lectures and one 50-minute tutorial per week for 12 weeks, though in-term quizzes reduce the number of lectures to 33. There is a three-hour final examination. The pedagogical impetus for the course was influenced by changing biochemistry degree requirements at the time. The perennial question of `what must be left in, what can be taken out, and what should be added' was about to result in the deletion of certain ancillary chemistry courses from the core biochemistry programme. The ratinale was to increase flexibility and to make room for new biochemistry courses. This meant deletion of the one and only inorganic chemistry course then required. Fortunately, a compromise was achieved. The biochemists agreed (bless them!) to retain the inorganic chemistry component, provided that it was the new bioinorganic course. The course is an elective rather than a requirement for chemistry majors. Additionally, many biology students elect to take it, and the prerequisites are arranged so as not to deter this. Obviously, then, the class is usually quite inhomogenous, attracting students with quite varied background, accomplishments and ultimate objectives - factors that add to the challenge in presenting a course that is intellectually satisfying, yet accessible. This is one course students are advised to take as late in their programmes as reasonable and convenient, so that they will have reached the level of experience and maturity necessary to handle cross-disciplinary subject matter and to remedy on their own any individual deficiencies in background knowledge.
There are two recommended text-books: M.N. Hughes Inorganic Chemistry of Biological Processes (Wiley-Interscience, New York, second edition, 1981) and R.W. Hay, Bio-Inorganic Chemistry (Halsted Press, New York, 1984). These are rather parallel in organization and content, and the course is structured in a similar manner (see Table 1). Neither book is judged wholly satisfactory, thus they are `recommended' rather than `required' for the course. In each book, the selection of topics and depth of coverage is uneven, and the fast pace of development has made both rapidly out-of-date. As a result, the lectures contain considerable material gleaned from the numerous monographs and review articles on aspects of bioinorganic chemistry, as well as items from the original literature. While the class is expected to have read the textbook coverage on each topic, the main delivery of material is by way of lecture notes and duplicated handouts. A substantial reading list is provided and a selection of books and articles is placed on library reserve. These resources include standard inorganic textbooks, most of which have a good presentation of fundamental transition-metal theory and spectroscopy (the areas that students find the most difficult), and some of which have useful chapters on bioinorganic chemistry as well. An example is the text by F.A. Cotton and G. Wilkinson Advanced Inorganic Chemistry (John Wiley, New York, 5th edition, 1988). It is perhaps worth re-emphasizing our course is concerned with the application of inorganic chemistry to biological processes, and is not a course in biochemistry.
At the Start
The first lecture is always a crucial one; here, at the start, the sense that there is much of interest to be learned, and that the course will be stimulating, enjoyable and worthwhile, can be promoted by careful selection of the topics. The students all have some idea about photosynthesis, even if they lack knowledge of the converse process, respiration. These two examples are used descriptively to make them aware of the involvement of iron, manganese and copper (not forgetting magnesium!) in these fundamental processes so often shown as just reactions of carbon dioxide and water, or of sugars and dioxygen, respectively. The lecture proceeds with a discussion of the various structures of the iron and copper proteins involved (cytochromes, ferredoxins and plastocyanins) and shows that we currently know rather less about the manganese site implicated in the water-splitting step. It concludes with a brief descriptive survey of several other important metalloproteins that will be met in the course, emphasizing those of known structure, to underline the great variety of structural types and function exhibited by metals in biological systems. The second introductory lecture follows with a rapid sketch of each of the important metals; their biological occurrence, distribution, concentrations, roles, and the consequences of deficiency or excess. Finally, there is a quick review of some basic biochemical topics so as to alert those students with deficient backgrounds that they will need to remedy the situation if they are to cope with later material.
Approximately one-third of the course is taken up with the fundamental chemistry of d-block elements. The coverage is not from a preparative or descriptive standpoint, but rather to emphasize the special properties afforded by valence-shell d-electrons and how they are modelled by simple theory. The level of coverage is typically that of chapters 18-21 of A.G. Sharpe's book Inorganic Chemistry (Longman, London, second edition, 1986). As the major part of the course is taken up by the bioinorganic material, it is necessary to be fairly brief and selective, compared to the content of the SFU course "Chemistry of the Transition Metals". For example, symmetry and group theory concepts are omitted, the interpretation of d-d spectra from Orgel and Tanabe-Sugano diagrams is simplified somewhat, and, even though metalloprotein sites are rarely regular, there is less time to discuss in detail any stereochemistry other than octahedral or tetrahedral. Throughout the course, every attempt is made to illustrate points using actual metalloprotein situations or other biologically relevant examples, rather than just simple ligands and complexes. In addition, there is a vocabulary, language, and methodology that inorganic chemists use in dealing with transition metal complexes and their properties. Hence one aim is that the students should come out of the course functionally literate in this field, whatever their background or future direction may be.
The discussion of individual topics in bioinorganic chemistry occupies the remaining two-thirds of the course. The material in the two recommended textbooks is used as the basis of the lectures, but it is significantly updated by inclusion of more recent results and opinion derived from current literature and review articles. A favourite way to convey the excitement of this topical, live, and developing subject is with transparencies of recent items that have hit the `scientific headlines' in such journals as Chemical and Engineering News, Nature and Science. Each time that I have taught the course, there has been at least one major event of this type to report, such as the discovery of a vanadium nitrogenase. And as usual, the judicious use of simple models and demonstrations is always appreciated.
The purpose of the course is not the thoughtless rote learning of the subject matter, although clearly considerable retention of `factual material' must be expected. Rather, it is hoped the class will take away an appreciation of the special properties that accrue to transition metals; the properties that impart unique features in the biological context; the methodologies available to the bioinorganic chemist for the exploration, understanding, and modeling of the biometallic system; the present limitations of our understanding; and the important fronts on which the subject is moving.
Undoubtedly reality falls somewhat short of these ideals. Nevertheless, it is our experience that the course is immensely popular with a wide variety of students, and that to teach it is a most stimulating, rewarding, and enjoyable challenge.
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|Publication:||Canadian Chemical News|
|Date:||Mar 1, 1990|
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