Univ. Prof. Dr. Leticia González Institute of Theoretical Chemistry University of Vienna

Transcription

1 Univ. Prof. Dr. Leticia González Institute of Theoretical Chemistry University of Vienna PLUS LUCIS 70. FORTBILDUNGSWOCHE

2 Molecules dancing waltz Let s go to the opera!

3 Molecules jiggling and wiggling Everything that is living can be understood in terms of the jiggling and wiggling of atoms." Richard Feynman, Picture: en.wikipedia.org

4 Questions But why do atoms and molecules jiggle and wiggle? How fast do they move? Can we watch them as they dance?

5 The Dancing Floor of molecules Potential energy surfaces The alps between Vienna and Graz picture: wikimedia.org

6 Potential energy surfaces The alps between Vienna and Graz Satellite view picture: maps.google.com

7 Potential energy surfaces The alps between Vienna and Graz Topological view picture: maps.google.com

8 A hike through the mountains Molecules do it similarly a hike through the potential energy landscape product reactants Example: [4+2]cycloaddition

9 A hike through the mountains Molecules do it similarly a hike through the potential energy landscape product transition state reactands picture: maps.google.com

10 A hike through the mountains What we have seen so far: Over the mountain Reactants Products

11 Tunneling Molecules can do much more: Through the mountain Reactants Products

12 No classical tunneling

13 Photochemistry With light molecules get excited and can dance in a different potential energy Reactants Products

14 Photochemistry and slide down via surface crossings! Example: [2+2]cycloaddition

15 How fast the atoms move? Ranges for chemical reactions : 1 Å Particle s average velocity: 1000 m/s t = s = 100 fs

16 What is a femtosecond? 1 fs = s s km 1 s In 1 fs light travels 300 nm (size of a large virus)! Hydrogen molecule make 1/8 vibrations Electrons orbits 8 times around a H atom If 1s 1 fs Age of the universe 7 min

17 Making movies In 1878 the photographer Muybridge was able to capture movement with the fastest camera of the time.

18 Slow motion = super fast shutter speed htttp://knowledge video.ga

19 Catching molecules in the act Femtosecond time resolved spectroscopy Molecular Beam Probe (Observation pulse) Detector Pump (Start pulse)

20 Femtochemistry es.wikipedia.org Nobel lecture in 1999: Freezing time In a femtosecond lecture.html What femtosecond spectroscopy can study: Ahmed Zewail Ultrafast Reactions knowledge about the Reaction mechanisms Transition states Ultrafast Structural Relaxation Structural changes on the potential energy surfaces

21 NaI dissociation: the Nobel reaction AG González A. H. Zewail and coworkers (1988)

22 Watching NaI dynamics AG González

23 Watching NaI dynamics AG González

24 Watching NaI dynamics AG González

25 Watching NaI dynamics AG González

26 Watching NaI dynamics AG González

27 Watching NaI dynamics AG González

28 The role of theory Simulation of time dependent chemical processes Time-dependent Schrödinger equation Calculation of potential energy surfaces for ground and excited states Time-independent Schrödinger equation

29 The role of theory Simulation of time dependent chemical processes Time-dependent Schrödinger equation Calculation of accurate potential energy surfaces for ground and excited states Time-independent Schrödinger equation

30 The challenge de.wikipedia.org The underlying physical laws necessary for the mathematical theory of a large part of physics and the whole of chemistry are thus completely known, and the difficulty is only that the exact application of these laws leads to equations much too complicated to be soluble. P. A. M. Dirac, 1929 It therefore becomes desirable that approximate practical methods of applying quantum mechanics should be developed, which can lead to an explanation of the main features of complex atomic systems without too much computation.

31 Computational Chemistry Nobel prize in Chemistry in 1998: Walter Kohn "for his development of the densityfunctional theory" and John A. Pople "for his development of computational methods in quantum chemistry". Walter Kohn John A. Pople Nobel Prize in Chemistry 2013: "for the development of multiscale models for complex chemical systems". Martin Karplus Michael Levitt Ariel Warshel

32 Chemistry on supercomputers zid.univie.ac.at

33 What is inside a supercomputer? VSC3: processors (32320 cores) -126 Terabytes of memory (1000 GB= 1 TB) -Under the top 100 (top 85) A standard PC: Picture: Claudia Blaas Schenner/vsc -1 processor (4 cores) -4 GB

34 Computational (photo)chemistry QUANTUM MECHANICS fs to ps Molecular Dynamics SEMICLASSICAL fs to ps Quantum chemistry CLASSICAL MECHANICS fs to s Full understanding of chemical reactions

35 Hop-on hop-off bus tour

36 Guiding organic synthesis Enviromentally friendly synthesis guided by computational chemistry! L. Xie, S. Niyomchon, A. Mota, L. González, N. Maulide Nat. Commun. DOI: /ncomms10914, (2016)

37 Explaining photostability of nucleobases DNA/RNA nucleobases Felix Plasser ChemPhysChem 11, 3617 (2010) J. Phys. Chem. Lett. 3, 3090 (2012) ChemPhysChem. 14, 2920 (2013) Phys. Chem. Chem. Phys. 16, (2014) J. Am. Chem. Soc. 137, 4368 (2015) Topics in Current Chemistry 355, 99 (2015)

38 e.g. Deactivation of cytosine Semiclassical molecular dynamics simulations discloses the different deactivation mechanisms ChemPhysChem 11, 3617 (2010) ChemPhysChem 14, 2920 (2013)

39 Nucleobases vs thionucleobases Red shifted absorption Much better UV B absorber

40 Nucleobases vs thionucleobases Nucleobase analogues exhibit different properties than nucleobases: Fast ground state relaxation (photostable) Minor triplet population No ground state relaxation 100% triplet yield (biradicals)

41 Deactivation of thiouracil after UV irradiation Ab initio molecular dynamics simulations over 1ps Performed in the VSC3, 1.8 million core hours (~2 months in 1600 cores). About ~50 years in a normal PC with 4 cores...

42 Different photochemistry

43 From damage to therapy The similarity of nucleobases analogues is a threat but also an opportunity! io9.gizmodo.com Thiobases as TROJAN HORSES? Photoactivation of DNA thiobases as a potential novel therapeutic option.

44 Anticancer therapies Cancer cells replicate faster than normal cells DNA is the ideal target molecule for anticancer drugs PHOTODYNAMIC THERAPY (PDT) A drug attacks the cancer cell Irradiation of light triggers generation of reactive oxygen species Oxidation of DNA helix CHEMOTHERAPY Drug DNA complex formation Distortion of DNA helix blocking of cell replication

45 Photodynamic Therapy (PDT) tumor tissue DRUG Cell membrane DRUG Cell nucleus DRUG Oxidative Species 1 O 2 Apoptosis

46 PDT drug going through the cell membrane Classical dynamical simulation during 250 ns with ca atoms 20 ns/day on GPU vs ns/day on CPU (2 weeks instead of 3.5 years) Classical molecular dynamics simulations UNRAVELS THE MECHANISM of absorption and the factors which favor the process

47 How does PDT drug bind to DNA? Minor groove -7.3 kcal/mol Intercalation kcal/mol Molecular dynamics simulations provide the affinity of the drug to DNA Biochemistry 53, 2391 (2014)

48 How does the drug interact with light? light In water In DNA Vacuum Multiscale calculations reveal the states involved and the effect of environment Angew. Chem. Int. Ed. 54, 4375 (2015)

49 Summary Using computer simulations it is nowadays possible to observe the motion of molecules in real time, allowing to: Explain reaction mechanisms Predict reactivity Manipulate and control functionality

50 Thanks