(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):

RASGAP

GTP

~ 40 ÅQM part: 45 atoms MM part: 1608 atomscollected in 483 EFs

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

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)

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

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

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

Epidermal Growth Factor Receptor Pathway

Dendrimers

Dendrimers

Large number of micro-environments with different properties

Gold Nanoparticles

Gold Nanoparticles

Buckyball (left)500 atoms3000 electrons

Gold Particle3000 to 30000 atoms500,000 electrons

Problem grows as Ne2