(Salen)Mn(III) Compound as a Nonpeptidyl mimic of Catalase Catalase 2H 2 O 2 2H 2 O + O 2 An...
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Transcript of (Salen)Mn(III) Compound as a Nonpeptidyl mimic of Catalase Catalase 2H 2 O 2 2H 2 O + O 2 An...
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(Salen)Mn(III) Compound as a Nonpeptidyl mimic of (Salen)Mn(III) Compound as a Nonpeptidyl mimic of CatalaseCatalase
Catalase2H2O2 2H2O + O2
N
O
N
O
Mn
RR
X X
Y Y
Cl
An incomplete list of possible treatment applications:Alzheimer’s diseaseStrokeHeart diseaseAgingCancer (reduction of the side effects, allowing higher drug doses to be administered)
Substituents change enzymatic activity:Substituents change enzymatic activity:the biomimetic can be tuned structurally and electronically the biomimetic can be tuned structurally and electronically
Intelligent design of Biomimetics (Synzymes):Intelligent design of Biomimetics (Synzymes):
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RASGAP
GTP
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~ 40 ÅQM part: 45 atoms MM part: 1608 atomscollected in 483 EFs
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2.0
2.5
3.0
3.5
02468
10121416182022242628303234
1.82.0
2.22.4
2.62.8
3.0 3.2 3.4 3.63.8
Potential energy surface for the GTP hydrolysis for the RAS/GAP complex model (calculated at the B3LYP/4-31G*/3-21G level)
E(k
cal/
mo
l)
R[O(W)-P]
R[P-O(P)]
Reactionpath
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Characterization of Ping-Pong Mechanism for Characterization of Ping-Pong Mechanism for Dismutation of HDismutation of H22OO22 MoleculeMolecule by (Salen)Mn(III)by (Salen)Mn(III)
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Mechanism-Based Structural Tuning of Catalase Activity Mechanism-Based Structural Tuning of Catalase Activity of Salen-Manganese Complexes for R=OMe substituted of Salen-Manganese Complexes for R=OMe substituted
compoundcompound
Abashkin, Burt Inorg. Chem., 2005; Abashkin, Burt Phys. Chem. B, 2004
Estimated computer resources needed for the exhaustive tuning :
50-60 (substituted biomimetics) x 200-400 (hours of large CPU) = YEARS
Dramatic increase in computation power is needed to solve the problem
Dramatic increase in computation power is needed to solve the problem
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Computational assistance in developing Computational assistance in developing novel biological nanodevices:novel biological nanodevices:
Target
DNA/RNA Target
“Simple” Nanoprobe for detecting biowarfare reagents and genetic diseases.
Red light
FluoresceinGreen Light
Recognizer Recognizer
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Practical development of Nanoprobe needs optimization of various elements:Practical development of Nanoprobe needs optimization of various elements:
Target
Rod
Polyethylenglycol (PEG) tether
Recognizer Recognizer
Linker
Fluorophores
Computational support includes QM ( hundreds of atoms) and MM (thousands of atoms) calculations and/or complex
QM/MM simulations
Computational support includes QM ( hundreds of atoms) and MM (thousands of atoms) calculations and/or complex
QM/MM simulations
Feasible only on a supercomputer
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Epidermal Growth Factor Receptor Pathway
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Dendrimers
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Dendrimers
Large number of micro-environments with different properties
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Gold Nanoparticles
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Gold Nanoparticles
Buckyball (left)500 atoms3000 electrons
Gold Particle3000 to 30000 atoms500,000 electrons
Problem grows as Ne2