41
It was 1978/1979. Soon I realised that our Austrian education in chemistry provided an excellent basis for the advancement in new fields. At Barry Karger’s labs I started to work in the field of enantiomer separations, a hot topic at that time. Via my background in organic and pharmaceutical chemistry and bridging it with up- to-date separation technologies lead us quickly to a level where I earned some recognition worldwide. This was the start of becoming a ‘chiral technology’ specialist working in various areas of chirality driven research niches. It accompanied my scientific and academic life thereafter. To date I am still fascinated by chirality and what can be discovered along that line.
Returning from Boston to Graz I finished the Habilitation in Pharmaceutial and Analytical Chemistry in 1982. Then I was offered good working opportunities in Graz, so I decided to stay there. In the mid-80s I patented together with a colleague from the Organic Chemistry Department, Georg Uray, a methodology to prepare, on a large scale, enantiomerically pure betablocker type drugs. This technology could be licensed to companies in the pharmaceutical industry and we also sold the products to Aldrich etc. It was the start of my entrepreneurship which was chequered with several other, more or less successful, patent applications.
Based on my steadily growing standing as separation scientist with particular know-how in enantiomer separation I was then invited to the FDA in Washington DC by Irving Wainer to take up a position as a Visiting Scientist (1986/1987). However, due to re-arrangements within the FDA, I ended up in Bethesda working on peptides and antibodies. For me it was an entirely new field, but at the end it was very fruitful as I could expand my know-how substantially.
Was working in the USA very different from Europe?
In the years 1978 and before we in Austria at the universities were still a bit behind the level of modern instrumentation compared to Switzerland and Germany where I had already been working previously (e.g. Sandoz-Basel). At Barry Karger’s labs in 1978/79 the instrumentation was not much better than here in Austria; they had just a bit more instruments installed. Nevertheless there was a clear difference in the availability of consumables, chemicals etc. due to a much better funding. In Boston I learnt that if you want to be competitive in science and to be fast in publishing just order the consumables you need via a phone call and do the experiments you have envisioned. Do not waste time since outside there is competition! One wants to be the first and this in turn is necessary for successful grant applications.
Nowadays we have adopted a similar attitude at least in my labs, but 20 years later. However, one has to confess that this attitude is really wasteful and a lot of not so fruitful experiments get made and discarded. However one needs also to make a number of ‘wasteful looking experiments’ in order to find new routes. It is the concept of serendipity if we learn from all these type of ‘negative’ but also ‘surprising’ looking results. To summarise, yes, in Boston I learnt to accept competitiveness in science, the run for being the first in publishing results and the run for project money via the writing of research proposals, creating cooperations with industry which in the USA has a much better attitude to supporting research.
I also learnt in the USA that you as a person gets credit upfront; you may fulfil the expectations or you may fail. However if you have failed you get a second chance which was (is) a bit different to our culture.
When did you first start making your own chiral stationary phases (CSPs)?
As I have already intimated, I started to make my own CSPs in the
early 80s after I returned from Barry Karger’s labs. These phases dealt with chiral ligand exchange chromatography. In parallel we developed π - π selective phases as in the 80s I was already working extensively on column switching and multidimensional LC-LC systems. To understand and to improve chromatographic selectivity was always a major focus. None of the early phases have been commercialised but it changed when we developed the ULMO phase together with G. Uray and N. M. Maier. These CSPs attracted interest from the Regis company in the USA who scaled up the synthesis and launched the product onto the market.
In parallel I developed the idea of generating chiral ion exchangers. As it was unique at that time we patented the concept and the material of QN-AX and QD-AX columns in the hope that chromatographic column producers would get interested in the concept and launch the columns. The dream worked and after the Bischoff company the world market leader in chiral columns, Chiral Technologies Europe (CTE) licensed the patent exclusively. The columns have now been on the market for about 20 years.
Following this concept we subsequently developed and then patented chiral cation exchangers and chiral zwitterionic ion exchangers. The latter CSPs are now sold by CTE as ZWIX(+) and ZWIX(-) columns. As you know they work nicely for the resolution of ampholytes. Chiral ion exchanger type CSPs and columns relate to a niche type application area in comparison to the polysaccharide type CSPs. However they offer the opportunity to deal also with very polar compounds which can only be dissolved in water or water-based media. This is a clear advantage. All the CSPs we developed are offered in analytical column formats but also in preparative scale. In summary, the chiral ion exchanger materials as such stand out from the many other chiral materials available from various companies. From the molecular interaction mechanism they represent clearly unique materials.
Lindner’s zwitterionic chiral stationary phase launched by Daicel in 2012 as CHIRALPAK®
ZWIXTM
What do you regards as your main chromatographic achievements outside of your work on chiral separations?
As I said before, the tuning and understanding of ‘selectivity’ as the key parameter in chromatography was always in focus of my work. What can be learnt from ‘enantioselectivity’ is valid in a broader sense. Therefore in the past ten years we have also developed various HILIC type phases and columns in order to understand better the HILIC type selectivity space. We have also developed affinity type stationary phases to mimic bioaffinity type selectivity and property profiles for antibody purification.
In summary, over the many years of my engagement in chromatography I have been working with (a) normal phase chromatography using silica, (b) extensively with reversed phase
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48
