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Antioxidant effects of C60 derivatives
A DFT study of the reaction mechanism
M. Swart, S. Osuna and M. Solà[email protected]
Objective:systems in
biomedicine
2
Reactivity and chemical bonding in biomedicine
• Reactivity and regioselectivity endohedral fullerenes
• Chemical bonding in DNA triplexes
3
Reactivity and chemical bonding in biomedicine
4
• Nanocages: reactivity and chemical bonding– 662 atoms
background:parallellization on
MareNostrum
5
Parallellization on MareNostrum
• Programs used:– ADF version 2007– Open-MPI
• ADF example:– Ptcomp_METECC
• DFT functional: BP86
• Basis set: DZP orTZP
• Pt(PPh3)3CO (105 atoms)
6
Parallellization on MareNostrum
cpus
sec. DZP
red. sec. TZP
red.
4 3165
8 1717 0.54
8681
16 932 0.54
4395 0.51
32 580 0.62
2515 0.57
64 372 0.74
1512 0.60
128 300 0.86
998 0.66
• Good performance of up to at least 64-128 cpus
• Annual report BSC 2007• p. 224-225
7
background:fullerenes
8
Structure and discovery of fullerenes
• Kroto, Smalley and Curl tried to simulate the conditions of the giant red stars in the laboratorium, and noted in the mass spectra the appearance of peaks corresponding to 60 and 70 atoms.– Nature 1985, 318, 162
C60: buckminsterfullerene
Buckminster Fuller’s geodesic dome (Expo ’67 Montreal)
C60
C70
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Metallofullerenes
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Heterohedralmetallofullerene
Exohedralmetallofullerene
Endohedralmetallofullerene
The so-called TNT (trimetallic nitride template) endohedral fullerenes are most studied, because they are obtained in macroscopic quantities.
Sc3N@C80, Sc3N@C68, Sc3N@C78
computationaldetails
11
Computational details
• Programs used: ADF version 2007QUILD (model Hessian TS !)
• DFT functional used:BP86• Basis set: DZP for optimizations, frozen-core• Relativistic corrections: ZORA• Single-points: BP86/TZP//BP86/DZP
• Additional software: program POAV3
• All TSs have been characterized through the calculation of theanalytical frequencies, to have one (and only one) imaginary frequency – MareNostrum, Barcelona (32-64 processors, 96 hours)
12
At this level of theory the barrier is underestimated by ca. 6 kcal·mol-1
Barrier parent Diels-Alder reaction: 18.6 kcal·mol-1
J. Comput. Chem. 2008, 29, 724-734
results:previous reactivity
studies (BSC)
13
Reaction studied
• Study of the Diels-Alder reaction
• Study of:– thermodynamics– kinetics
14
C78 butadiene
M3N@C78 butadiene
M=Sc,Y
J. Am. Chem. Soc. 2009, 131, 129-139J. Am. Chem. Soc. 2008, 130, 6206-6214
Reactivity of non-equivalent bonds of free C78 and Sc3N@C78
15
We have studied the Diels-Alder reaction over the 7 non-equivalent [6,6] bonds, and over the the 6 non-equivalent [5,6] bonds.
J. Am. Chem. Soc. 2008, 130, 6206-6214
Bonding model: Ionic (Sc3N)6+@C786-
Reaction barriers (kcal/mol)
16
[6,6] Pyracilenic
[6,6] Pyracilenic [5,6]
Corannulenic
[6,6]Type B
[6,6]Type B
[5,6]Corannulenic
Barrier parent Diels-Alder reaction: 18.6 kcal·mol-1
J. Am. Chem. Soc. 2008, 130, 6206-6214
Comparison of Y3N@C78 and Sc3N@C78
• We have studied the DA reaction over all non-equivalent bonds:
– 13 in D3h-C78, 13 in D3h-Sc3N@C78
– 24 in Y3N@D3h-C78
17J. Am. Chem. Soc. 2009, 131, 129-139
Regioselectivity of the reaction is clearly determined by the encapsulated cluster inside the cage:
free: b, 1, 7
Sc3N: 6, 4, c
Y3N:d, 6, 4
Short [6,6] bonds Situated far away from the Sc3N influence
Large [5,6] bonds + close to Y3NShort [6,6] bonds + far away from Y3N
Short bonds, preference for [5,6]
Preferences Sc/Y D3h-C78
18J. Am. Chem. Soc. 2009, 131, 129-139
Sc
ScSc
Y
Y Y
D3h-C78
YY Yh
h= 0.69 Å
d
h= 0.60 Å [0.55,0.73]
hY
Y Y
Edef(diene)= 12.9 [12.9,27.1]
distdist= 1.69 Å
YY Y
dist= 2.20 Å
+ :CH2
Why is large bond d so reactive in Y3N@D3h-C78 ?
19J. Am. Chem. Soc. 2009, 131, 129-139
Reactivity of Ng@C60 and Ng2@C60
• Encapsulation of noble gas dimers may lead to Ng2 chemical bond
• Krapp, Frenking, Chem. Eur. J. 2007, 13, 8256-8270
• Effect on reactivity unknown– difficult to predict because of opposing effects
• reduction of electron affinity• increase of pyramidalization
20Chem. Eur. J. 2009, in press
Reaction barriers (kcal/mol) for Ng2@C60
21Chem. Eur. J. 2009, in press
results:antioxidant effects
22
Fullerene derivatives for superoxide dismutation
• Antioxidant activity of C60 derivatives– carboxyfullerene
tris-malonyl C60 (C3)
– degradation of damaging superoxide O2
– • radical
• Possible future application in (bio)medicine– mechanism of action is
currently unknown
23
• C3 compound
submitted
Proposed reaction mechanism carboxyfullerene C3
24submitted
Energy profile (kcal/mol)
25submitted
Low barriers
Deactivation of superoxide radical
• TS1 • TS2
26submitted
concludingremarks
27
conclusions
• ADF well parallellized– suitable for use on MareNostrum (RES)
• Exohedral fullerene reactivity depends very much on encapsulation (M3N, Ng, Ng2)
• Mechanism of action of superoxide dismutation by carboxyfullerene shown
• Computing time on RES-resources vital for these studies
28
acknowledgments
29
Collaboration metallofullerenes:Josep Maria CampaneraJosep Maria Poblet
Girona Seminar 2010
• IX Girona seminaron Electron Density, Density Matrices, and Density Functional Theory
– July 5-8, 2010
– dedicated to 70th birthday of Prof. Ramon Carbó-Dorca
– more info: http://iqc.udg.edu/gs2010
30