The desire to explore our surrounding world has always been one of the strongest charac- teristics of human nature. Columbus and the great explorers travelled outwards and discovered new continents in the 16th century and Bohr, Einstein, Rutherford, Curie and many others travelled inward to explore the secrets of the atomic world in the 20th century.

Explorers use ships, planes or spacecraft to travel outward and they use increasingly Femtochemistry and Femtobiology

(ULTRA) sophisticated scientific tools to travel inward An ESF scientific programme into the world of atoms and molecules. Here at the beginning of the 3rd millennium we have microscopes allowing us to see single atoms and telescopes allowing us to see the edges of the universe. At the end of the 20th century a fascinating new tool, the femtosecond laser, was developed. The femtosecond laser provides us with ULTRA short light pulses, allowing the motion of atoms and molecules to be captured as if they were filmed. To have, not only the structure of atoms and molecules, but also their motion, is of unique importance in our quest to understand and control chemical and biological processes.

The ULTRA Programme, sponsored by the European Science Foundation, is a collabo- rative effort among the leading European laboratories engaged in using femtosecond laser pulses in chemistry and biology, a field of research with its own name: Femtochemistry and Femtobiology. In this brochure we give a brief introduction to the The European Science Foundation acts field and illustrate the activities within the as a catalyst Programme with a few illustrative case for the development stories. of science by bringing together leading scientists and funding agencies to debate, plan and implement pan-European initiatives.

1 Aims and objectives

By focusing on the ultrafast timescale of femtoseconds (1fs=10-15), this Programme’s aim is to improve our understanding of dynamics – how systems move between apparently equilibrated structures, changing their chemical composition and performing biological functions on the way. It will exploit new and emerging extensions of ultrashort pulse applications such as time resolved (fs) single molecule spectrosco- py, scanning two-photon fluorescence microscopy and fs X-ray pulse generation.

Femtosecond case stories Introduction

Taking pictures of chemical reactions The ultrafast time scale of femtoseconds The art of high speed photography is the time scale of elementary chemical started in 1877 when Eadweard Muy- reactions and of electronic and nuclear bridge, as a result of a bet, took a series motions in molecules: when chemical of snapshots of a galloping horse, to bonds are formed or broken during chemical prove that the horse at some point has all reactions, when molecules rearrange to four hooves off the ground. By freezing form new molecules, or when energy is transported from one molecule to another, the motion of the horse one can directly all these processes take place on a femto- study the pictures and learn about gallop. second time scale. Thus our fundamental understanding of chemical and biological processes ultimately relies upon a thorough understanding of the ultrafast processes.

Femtosecond lasers have been applied to most areas of chemistry and many molecular mechanisms in biological systems have been established. With the emergence of new and highly reliable techniques, completely new applications of ultrashort pulses come within reach: When the chemical bond between the red and 1 femtosecond (fs) Time resolved single molecules spectroscopy, green molecules above are broken the molecules corresponds to move apart at a velocity close to 1 km/s. With the 0.000000000000001 scanning two-photon fluorescence femtosecond laser we can directly monitor this motion second, in scientific microscopy, X-ray pulse generation, non- and get detailed information on how and how often notation 10-15 thermal micro-machining and coherent the molecules collide with neighbour molecules. In second. control of reactions, etc. All these new particular the communication between the molecules is of prime importance in order to get a deeper • In 1 fs light will extensions of ultrashort pulse applications understanding of chemical reactions. In simple terms travel only 0.3µm. will, together with existing applications, be we have to learn the language spoken among • 1 fs is to 1 sec. important topics of this ESF Programme. molecules. In principle we know quite well the what 5 minutes is to structure of individual molecules, but we only have a the age of the limited insight into way in which molecules interact universe with each. Femtosecond lasers have proven to be a • The shortest laser very capable translator of the molecular language. pulse to date is 4 fs.

2 In a similar way it would be desirable to Alignment of molecules freeze the motion of atoms and molecules In a chemical or bio-chemical reaction, while they are involved in chemical the orientation of the reacting molecules reactions. One of the scientific milestones plays a determining role for the outcome achieved using femtosecond lasers was the of the reaction. Using intense ultrashort use of these lasers to take pictures of laser pulses, a technique has been chemical reactions while they take place. developed to control the alignment and The Nobel prize in chemistry 1999 was orientation of molecules. A powerful, but awarded to Ahmed Zewail for the non-resonant laser is used to orient the pioneering use of femtosecond lasers to molecules. Using linearly polarized light, study chemical reaction. they align the molecular axis of the molecules, and by adding an elliptically Micromachining polarized light beam, it is possible to fs-pulses can be very intense and therefore control the orientation of the molecular have unusual properties that are distinct plane in medium-sized organic molecu- from other lasers. les. The degree of alignment is monitored using ultrafast Coulomb-explosion of the When conventional lasers are used to molecules. machine (cut, drill, etc.) materials, they work through absorption of the powerful Ultrafast relaxation in water laser light. When femtosecond lasers are One of the most important questions in used for machining, they can use much chemistry and biology is how, and how lower power since the laser light is fast, energy is transferred in, and in concentrated in an ultrashort pulse. With between molecules. femtosecond lasers it is possible to machine without heating the material at all. This In a series of femtosecond experiments it has enormous implications for the use of has been investigated how lasers for surgical procedures, as it is intermolecular energy was transferred in possible, for example, to remove tissue liquid water. Using an infrared without inflicting any damage to nearby femtosecond pulse, the OH-vibration was tissue. Presently this is used for experimental excited in liquid water. The subsequent surgery in the eyes and in the spinal cord. fate of the excited water molecule was followed using a delayed and polarized infrared probe pulse. This enabled the researchers not only to see how fast the water molecules rotate, but also how fast the energy is transferred from one water molecule to its neighbour. Surprisingly, this energy transfer time in liquid water is extremely short, less than 100 fs, indicating an extremely efficient The two mechanism for energy transport in liquid pictures show water. The mechanism is linked to the the difference between unusual structural properties of liquid micromachining water, dominated by a network of strong a tooth with a hydrogen bonds between the individual standard laser water molecules. Given the importance and a femtosecond of aqueous environments, in particular in laser. biology, the discovery of the ultrafast

3 3 energy transport among OH-bonds also giving rise to a vision stimuli in the brain. provides new insight into the possible For the well-adapted eye (night vision) energy transfer between, for example, the sensitivity to individual light particles proteins dissolved in water. (photons) is extremely high, primarily because of the ultrafast initial twist. Ultrafast molecular biology Chemists call this “twist” a cis-trans There is no doubt that molecular biology isomerization, which is shown below for will play a dominating role in the 21st the retinal molecule. century. Many scientists predict that molecular biology will dominate the 21st Non-Linear Microscopy century as physics dominated the 20th In the last few years femtosecond pulses century. A key element in this develop- have caused a minor revolution in the ment is the humane genome project development of microscopes for bio- where researchers all over the world medical applications. Again, the fact that work to determine the DNA structure of the light is concentrated in a very short the human chromosomes. time-interval makes femtosecond laser light distinctively different from light Femtosecond lasers also play an important from normal sources. role in determining how bio-molecular structure and dynamics work together to define function. An interesting observa- tion is that in most, if not all, biologically important processes, like photosynthesis, the uptake of oxygen in the blood, vision, etc, start out in an initial, very fast (femtosecond) step. The purpose of the first step is to secure that no other interfering processes can take place and the faster the step, the more likely is the desired outcome of the reaction. The picture shows a cell culture which has been Femtosecond lasers A good example of this principle are the exposed to photofrin, a photo-activated drug used in provide new insight the treatment of cancers. The image was obtained using into the relationship fast structural changes taking place in the a non-linear microscope and images like the above between structure molecules responsible for vision. Using help researchers to gain more knowledge of the actual and dynamics and femtosecond lasers, researchers have mechanism by which photoactivated drug works. © M Nichols, Developmental Resource for Biophysical function of large bio- demonstrated how an ultrafast single twist Imaging Opto-Electronics, Cornell University molecules. around a chemical bond in the retinal © Chemistry Dept, Washington molecule is responsible for initiating the In non-linear microscopy, the femtosecond University complex bio-molecular response eventually laser is used to excite bio-molecules and the light emitted from these molecules is used to form an image. The lasers operate at long wavelengths (>800 nm) which can penetrate into the tissue. For a normal laser operating at 800 nm there is not enough 11-cis-retinal energy to excite the bio-molecules. 11-cis-retinal However, with focussed ultrashort pulses Visible light 150 fs it is possible to excite the bio-molecules via absorption of two photons. With non-linear microscopy a good spatial resolution can be achieved in all three dimensions, enabling sectioning of the

all-trans-retinal all-trans-retinal studied sample and generation of three- dimensional pictures.

4 Funding

ESF scientific programmes are principally financed by the Foundation’s Member Organisations on an à la carte basis. ULTRA is supported by: ULTRA activities Österreichische Akademie der Wissen- schaften, Fonds zur Förderung der The ULTRA Programme offers support wissenschaftlichen Forschung, Austria; for the organisation of schools, practical Fonds National de la Recherche Scienti- courses and workshops in the field of fique, Fonds voor Wetenschappelijk femtochemistry and femtobiology and Onderzoek-Vlaanderen, Belgium; issues an annual call for proposals for Akademie ved Ceské republiky, these activities. Potential organisers of Grantová agentura Ceské republiky, schools, practical courses and workshops Czech Republic; Statens Teknisk- are strongly encouraged to choose Videnskabelige Forskningsråd, Denmark; focussed themes. Examples of subjects Suomen Akatemia/Finlands Akademi, of great current interest within the scope Finland; Centre National de la Recherche of the ULTRA Programme are: Scientifique, Commissariat à l’Energie . Electronic energy transfer and charge Atomique – Direction des Sciences de la separation Matière, France; Deutsche Forschungs- . Short pulse generation gemeinschaft, Germany; Magyar . Ultrafast processes in organic and Tudományos Akadémîa, Országos semiconducting materials Tudományos Kutatási Alap, Hungary; . Bioimaging Istituto Nazionale per la Fisica della . Biological reaction dynamics Materia, Italy; Nederlandse Organisatie . Liquid dynamics voor Wetenschappelijk Onderzoek, . Vibrational energy transfer Netherlands; Norges Forskningsråd, . Wavepacket dynamics and coherent Norway; Instituto de Cooperaçao control Ciêntifica e Tecnológica Internacional, . Elementary chemical reactions Portugal; Oficina de Ciencia y . Coherence in chemistry and biology Tecnología, Spain; Vetenskapsrådet, Sweden; Schweizerischer Nationalfonds The ULTRA Programme also offers zur Förderung der wissenschaftlichen support for short-term visits of one Forschung/Fonds National Suisse de la week to one month, to stimulate co- Recherche Scientifique, Switzerland; operation between research groups in The Scientific and Technical Research different European countries. Priority Council of Turkey, Turkey; will be given to younger researchers (eg Biotechnology and Biological Sciences PhD, post-docs) but applications from Research Council, Engineering and senior researchers will also be Physical Sciences Research Council, considered. These visits may also be United Kingdom. used for learning new techniques.

Further information on activities supported by the ULTRA Programme and on how to apply for support is available at www.esf.org/ULTRA.

5 5 ULTRA Steering Committee

Professor Villy Sundström 12489 Berlin Professor Jouko Korppi- 3001 Heverlee (Leuven) (Chair) Germany Tommola Belgium Lund University Tel: +49 30 6392 1401 University of Jyväskylä Tel: +32 16 327 496 Department of Chemical Fax: +49 30 6392 1409 Department of Chemistry Fax: +32 16 327 990 Physics E-mail: [email protected] PO Box 35 E-mail: mark.vanderauweraer Box 124 40351 Jyväskylä @chem.kuleuven.ac.be 221 00 Lund Dr. Demet Gülen Finland Sweden Middle East Technical Tel: +358 14 602 553 Professor Rienk Van Tel: +46 46 222 4690 University Fax: +358 14 602 551 Grondelle Fax: +46 46 222 4119 Physics Dept. E-mail: [email protected] Vrije Universiteit Amsterdam E-mail: 06531 Ankara Department of Physics [email protected] Turkey Professor Jean-Louis and Astronomy Tel: +90 312 210 5060 Martin De Boelelaan 1081 Professor Mats Almgren Fax: +90 312 210 1281 Ecole Polytechnique - 1081 HV Amsterdam Uppsala University E-mail: ENSTA Netherlands Department of Physical [email protected] Lab. Optique Appliquée Tel: +31 20 548 7930 Chemistry INSERM U275 Fax: +31 20 444 7999 PO Box 532 Professor Jan Hala 91128 Palaiseau Cedex E-mail: [email protected] 751 21 Uppsala Charles University France Sweden Dept of Chemical Physics Tel: +33 1 69 31 99 96 Advisory member: Tel: +46 18 471 3649 and Optics Fax: +33 1 69 31 97 95 Dr. Thomas Jovin Faculty of Mathematics Fax: +46 18 508 542 E-mail: Max Planck Institute for E-mail: and Physics [email protected] Biophysical Chemistry [email protected] Ke Karluvo 3 Dept of Molecular Biology 121 16 Prague 2 Professor Razi Naqvi Am Fassberg 11 Dr. Luis Arnaut Czech Republic Norwegian University of Postfach 2841 University of Coimbra Tel: +420 2 2191 1421 Science and Technology Chemistry Department 37077 Göttingen Fax: +420 2 2191 1249 Dept of Physics Germany 3000 Coimbra E-mail: 7034 Trondheim Tel: +49 551 2011 381 Portugal [email protected] Norway Fax: +49 551 2011 467 Tel: +351 239 852 080 Tel: +47 73 59 18 53 E-mail: Fax: +351 239 827 703 Professor Harald Fax: +47 73 59 18 52 [email protected] E-mail: [email protected] Kauffmann E-mail: University of Vienna [email protected] Professor Majed Chergui Institute of Physical Chemistry Mr. Neil Williams Université de Lausanne Währingerstrasse 42 Professor Imre Santa ESF Senior Scientific Secretary Institut de Physique de la 1090 Vienna Janus Pannonius University Ms. Pat Cosgrove Matière Condensée Austria Dept of General Physics ESF Administrator Faculté des Sciences, BSP Tel: +43 1 31367 2512 and Laser Spectroscopy 1015 Lausanne-Dorigny Fax: +43 1 310 4597 Institute of Physics European Science Foundation Switzerland E-mail: 7622 Pécs 1 quai Lezay-Marnésia Tel: +41 21 6923678 / [email protected] Hungary 67080 Strasbourg Cedex 3660 (secr.) Tel: +36 72 501 559 France Fax: +41 21 6923635 / Professor Sören Keiding Fax: +36 72 501 571 www.esf.org 3605 Aarhus University E-mail: [email protected] Tel: +33 (0)3 88 76 71 06 E-mail: Kemisk Institut Fax: +33 (0)3 88 37 05 32 [email protected] 8000 Aarhus C Professor Jesus E-mail: [email protected] Denmark Santamaria Professor Sandro De Tel: +45 8942 3333 Universidad Complutense For the latest information on Silvestri Fax: +45 8619 6199 Facultad de Quimica this programme consult the Politecnico di Milano E-mail: [email protected] Dpto de Quimica Fisica ULTRA home page:

d’ordre : 012707 Dpto di Fisica 28040 Madrid http://www.esf.org/ultra or ° Piazza L. da Vinci 32 Dr. David Klug Spain http://www.chemphys.lu.se/ 20133 Milan Imperial College of Science, Tel: +34 91 394 4207 esf/index.htm Italy Technology and Medicine Fax: +34 91 394 4135 Tel: +39 02 23 99 61 51 Molecular Dynamics E-mail: Cover picture: Ice, water and

Fax: +39 02 23 99 61 26 Research Group [email protected] clouds: water is essential to our épôt légal : août 2001 - N E-mail: Depts of Chemistry and existence and many new aspects [email protected] Biochemistry Dr. Mark Van der of water have been revealed London SW7 2AY Auweraer using femtosecond lasers. Professor Thomas United Kingdom Catholic University of © AWI-Bremerhaven Elsässer Tel: +44 171 594 5806 Leuven Max-Born-Institute Fax: +44 171 594 5806 Chemistry Dept August 2001 Rudower Chaussee 6 E-mail: [email protected] Celestijnenlaan 200F © European Science Foundation Impression : IREG Strasbourg - D

6