There have been developed various methods of determining the enantiomeric purity and absolute configuration of chiral compounds using NMR, the most common and versatile analytical method in organic chemistry. As one of these, there is the method to resolve enantiomer signals by using paramagnetic chiral lanthanide shift reagents. For example, the europium propylenediaminetetraacetate complex (Eu-pdta) was reported to be useful for assigning the absolute configurations of α-amino acids and α-hydroxy acids in D2O.1) However, it has been well known that lanthanide shift reagents generally have the drawback of causing line broadening, which is more serious when they are used in stronger magnetic field. Eu-pdta often caused heavy line broadening especially for the signals of α-amino acids even with 90 MHz 1H NMR and it could not be used for these substrates in high-field NMR because of serious line broadening. In recent years, Kabuto and co-workers have demonstrated that the Samarium complex (Sm-pdta) 1 is not as likely to cause line broadening in high-field NMR as Eu-pdta does and can be also used in determining absolute configurations of the α-amino acids.2) Observation of the chemical shift nonequivalence for several protons enabled by the use of high-resolution NMR increases the reliability of the assignment as in modified Mosher method.
Fig.1. 1H NMR spectra (400 MHz) of valine (0.06 M, [D]/[L] = 1/2.85) in D2O at pH 9.4.
Resolution of the enantiomer signals of α-amino acids
NMR measurement is carried out on D2O solutions of α-amino acids of pH 9-10, near the pKa of the substrates, where the best resolution is possible. The pH of the sample solution is adjusted with D2O solutions of NaOD (~2M and ~0.2 M for fine adjustment, added with a micropipet), and a D2O solution of DCl, if necessary. Use of the buffer solutions containing anions such as phosphate and carbonate cannot be recommended because of their possible coordination to the lanthanide ion. When a sample solution contains both D-isomer and L-isomer, 1 is directly added in small amounts to the sample tube (when the concentration of the amino acid is 0.06 M, an amount of reagent is approximately 5-20 mol% of a substrate), and is dissolved by shaking the tube. Figure 1 shows an example of the NMR resolution of the enantiomer signals of valine utilizing the above procedure (1H NMR: 400 MHz; [valine] = 0.06M; D/L ratio = 1/2.85; pH 9.4; [1a]/[valine] = 0.2). Since the complex 1 itself also possesses several broad signals in the range of 2-4 ppm, it is not the appropriate reagent to use for determining the enantiomeric purity. However, as in the above example, when the enantiomer signals can be resolved at the baseline without overlapping with the signals of the reagent, then the approximate D/L ratio can be obtained from the ratio of the integration (D/L = 1/3.02 in the above case).
Determination of absolute configuration:
(A) Enantiomeric mixture: When measurements of different types of α-amino acid (D/L = 1/2) are made under the above conditions, resolution of the enantiomer NMR signals yields the following results (See Table 1). The chemical shift differences between the enantiomer signals were determined for the enantiomeric mixtures of various α-amino acids under the conditions described above. Some results are shown in Table 1.
Table 1. Resolution of enantiomer signals of amino acids in the presence of 1a.
Here ΔΔδ is δ(L)-δ(D), and δ(L) and δ(D) indicate the chemical shifts of 1H signal due to L- and D-amino acids in the presence of 1a, respectively. As shown in Figure 2, in the presence of 1a, the H signals of the D-isomers appeared more upfield than those of L-isomers, while the signals of side chain protons of L-isomer resonated upfield compared with those of their counterparts. This relation was observed for almost all of the amino acids examined. Therefore, by observing the separation of H and side chain proton signals, it is possible to assign the absolute configuration of α-amino acids including those with unknown configuration.
Fig. 2. Relative position of proton signals of amino acid enantiomers in the presence of 1a.
(B) Single enantiomer: Actual samples are often enantiopure. It is possible to determine the absolute configuration of a single enantiomer, by conducting the two separate measurements in the presence of 1a and 1b and comparing chemical shifts of the corresponding signals. This is because the chemical shifts of the signals of the enantiomer at hand in the presence of 1b are the same as those of its enantiomer measured in the presence of 1a. The chemical shifts of the 1H signals of amino acid are sensitive to concentration, temperature and pH, thus strict control of these conditions is required as well as controlling the equivalence of each reagent. The optimal procedures is to first prepare two sample tubes containing equivalent amounts of a pH-adjusted sample solution. To one and the other tubes, add separately the same amount of D2O solutions of 1a and 1b (pH adjusted to 8), whose concentrations are the same, using microsyringes to conduct the measurements.
This method has also been applied to α-hydroxy acids at pH ~ 5 and the relation for the side chain protons shown in Figure 2 was consistently observed.3)
- 1)K. Kabuto, Y. Sasaki, J. Chem. Soc., Chem. Commun. 1987, 670.
- 2)A. Inamoto, K. Ogasawara, K. Omata, K. Kabuto, Y. Sasaki, Org. Lett. 2000, 2, 3543.
- Tokyo Kasei Kogyo Co., LTD., JP2002-80437.
- 3)K. Omata, K. Horie, K. Ogasawara, K. Kabuto, Y. Sasaki, Abstract of 8th International conference on Circular Dichroism2001, p.78.
Course Title: Denmark and the European Union
Part A: Course Overview
Course Title: Denmark and the European Union
Credit Points: 24
625H Economics, Finance and Marketing
Course Coordinator: Dr Foula Kopanidis
Course Coordinator Phone: +61 3 9925 5475
Course Coordinator Email: firstname.lastname@example.org
Course Coordinator Location: Bld. 80, Level 11
Course Coordinator Availability: By appointment only
Pre-requisite Courses and Assumed Knowledge and Capabilities
The internationalization of business has become increasingly important over the past three decades. From the relatively uncomplicated import and export transactions that primarily characterized ‘international’ business in the 1950’s and 1960’s, to the complex world of international financial and management practices currently undertaken by multinational companies, the business environment has evolved into a challenging, and often unpredictable, setting.
Notwithstanding the international nature of business, individuals often see the world from an ethnocentric perspective. Their view of the rest of the world is tinted by their experiences in their home country, in their home city. As a result, business practices may be one-dimensional, lacking the depth and expertise of a global standpoint.
One of the major objectives of this course is therefore to sensitize students to ethnocentrism and develop students’ understanding of cross-cultural differences. They will expose students to an environment that is significantly dissimilar to that of Australia and /or Asia. It will encourage students to see the world from different academic and business perspectives. As students, they will experience a university system that is unlike to that they know, while as potential business graduates, they will encounter practices that will broaden their knowledge and skills.
The establishment of the European Union (EU) and the introduction of the euro have transformed the international monetary system and the operation of international business. The EU represents more than 304 million inhabitants (cf. 284 million for the US and 127 million for Japan, 21% of world gross national income (cf. 31% for the US and 14% for Japan) and it is the second largest economy and financial market after the US. As a consequence, the unification of Europe has transformed the nature international business.
From an EU Member State perspective, the introduction the euro has provided several benefits. First, the euro has been beneficial for the States’ economies, bringing in particular stability, low interest rates and zero exposure exchange rate risk. Second, the euro has cut the cost of doing business and simplified cross-border trade. Third, the euro has resulted in greater competition and a wider choice of goods and services, stable prices and lower interest rates for the consumer. Finally, the euro has made traveling cheaper and easier by eliminating currency exchange charges.
Australia has significant interest in developments in the EU since it is one of Australia’s largest economic partners. Due to the increased economic stability in Europe, the EU is now a better trading partner. It provides new and easier trade opportunities for Australian companies and subsidiaries of Australian firms operating in the euro zone benefit from the absence of transaction costs and foreign exchange risk.
The combination of one market and one currency has greatly increased business opportunities in the EU by both broadening access to the EU market and by simplifying operating rules and costs. The expansion of the EU to include several countries from Central and Eastern Europe will result in a consumer market of over 480 million people. This will again increase trade opportunities for Australian firms.
Another major objective of this course is to enhance and broaden students’ knowledge and understanding of the European Union. In order to successfully attain this knowledge and understanding, students will study various aspects of the Danish economy, the country’s political and financial system and its cultural development, as well as the development and evolution of the European Union.
Objectives/Learning Outcomes/Capability Development
The Learning Outcomes of this course include:
- Analyse culturally variable business practices using an appropriate analytical model;
- Analyse your own attitudes, values, beliefs and prejudices;
- Identify potential barriers in cross-cultural communication;
- Assess the influence of cultural factors on the individual, on business and on professional behaviour;
- Analyse economic, business and financial systems;
- Ability to work effectively in multi-disciplinary teams.
Overview of Learning Activities
Specifically, the learning activities are:
- Identify and investigate selected aspects of Australian business practices and compare these to European business practices;
- Record observations and reflect on personal experiences identifying similarities and differences in the cultural approaches and interpretations of social and teaching and learning practices;
- Reflect upon the processes of cultural and social adjustment involved in living and studying in another culture;
- Investigate their cultural assumptions and their practices, and identify their effect on others;
- Report on an analysis of the destination country in the context of the European Union, incorporating both cultural and business dimensions;
- Attend and participate in lectures and/or site visits in European location; &
- Participate in workshop discussions and/or online discussions.
Overview of Learning Resources
Various learning resources are available online through myRMIT/Blackboard. In addition to topic notes; assessment details and a study schedule you may also be provided with links to relevant online information; readings; audio and video clips and communication tools to facilitate collaboration with your peers and to share information.
Resources are also available online through RMIT Library databases and other facilities. If you require assistance with the RMIT library facilities contact the Business Liaison Librarian for your school. Contact details for Business Liaison Librarians are located online on the RMIT Library website.
Additional resources and/or sources to assist your learning will be identified by your course coordinator will be made available to you as required during the teaching period. There is no prescribed textbook for this Program. However you will find a list of useful websites and textbooks in Part B.
Overview of Assessment
Assessment tasks may include:
Group assignment & presentation.
Exams x 2
Assignments x 2