Applications of molecular modeling in catalysis

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Applications of molecular modeling in
catalysis From homogeneous to heterogeneous
by Dr. R. Mahalakshmy Young Scientist NCCR
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Contents

• What is molecular modeling?
• How do we apply molecular modeling to homogeneous
  system?
• e.g Mn-salen (Jacobsens catalyst)
  catalysed epoxidation of olefin
• How do we apply molecular modeling to
  heterogeneous system?
• e.g Epoxidation of olefin by immobilized
  Mnsalen catalyst in MCM-41

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Introduction

• What is molecular modeling?
• It is a broadly generic term that defines the
  use of computers to study chemical systems, with
  an emphasis on the structure, properties, and
  activities of molecules.
• Who is molecular modeler or computational
  chemist?
• Those scientist who are specially trained in
  the technologies, techniques and tools of
  molecular modeling.
• Computational tools
• Both software and computer hardware
• Computing platform Ranging from simple desktop
  computers to the use of very high performance
  super computers
• Support tools Interface to the codes, data
  visualizers (programs that create images from the
  computed data)

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Methods

• Molecular mechanics (MM)
• Properties of the molecule can be
  calculated by measuring the motion of the atoms
  and the changing energies of the spring.
• ab initio quantum chemical methods
• Based on the results of calculating the
  wavefunction, other chemical properties and
  activities can be determined.
• (iii) Semi-empirical quantum chemical methods
• A portion of the calculation comes from
  experimental data and the rest comes from
  mathematics.
• (iv) Density Functional Theory (DFT)
• Determines molecular properties from
  calculating the electron density rather than from
  the wavefunction.
• Depending on how broadly one defines
  molecular modeling or computational chemistry,
  there are a number of other methods that can be
  considered.

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Types of calculations that can be performed on
the molecule

• Single point energies (molecular energies)
• Molecular orbital calculations, including
  determination of
• frontier orbitals
• Vibrational frequency calculations
• Reaction mechanisms and reaction path following
  studies
• Determination of IR and UV-Vis spectra
• Transition structures and activation energy
  diagrams
• Electron and charge distributions
• Potential energy surfaces (PES)
• Thermodynamic calculations

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Fundamental Uses

• Chemical structure, or geometry of the molecule
• Number and type of atoms, bonds, bond
  lengths, angles,
• and dihedral angles.
• Properties of system of molecules
• Basic characteristics of the molecule, such as
  its
• molecular energy, enthalpy, and vibrational
  frequencies.
• The activity or reactivity of a molecule
• Those characteristics that describe how the
  molecule
• behaves in the presence of other molecules,
  such as its
• nucleophilicity, electrophilicity, and
  electrostatic potentials.

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Other uses

• To model a molecular system prior to
  synthesizing that
• molecule in the laboratory.
• Understanding a problem more completely.
• Some properties of molecule can be obtained
  computationally
• more easily than by experimental means.
• e.g. Molecular bonding

Anyone can do calculations nowadays. Anyone can
also operate a scalpel. That doesnt mean all
our medical problems are solved.

-Karl Irikura
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Jacobsen epoxidation
Jacobsen Epoxidation Enantioselective synthesis
of epoxides from isolated alkene.

• Jacobsen's catalyst
• The commercially available '1994 reagent of the
  year.
• Converts achiral olefins to chiral epoxides with
  enantiomeric
• excesses regularly better than 90 and
  sometimes exceeding
• 98.
• To date, the origin of this dramatic selectivity
  has not
• been explained.

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Catalytic cycle involved in the epoxidation
Step1An oxidant transfers atomic oxygen to the
MnIII catalyst (the oxygen presumably
coordinates to the metal in a site
normal to the salen plane) Step2The activated
oxygen is then delivered to the alkene.
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Three possible modes of oxygen delivery
Mechanisms of oxygen transfer from the catalyst
to the olefin
Step A Attack of an oxygen radical intermediate
on the double bond Step B
Concerted oxygen delivery Step C Formation of
a metallaoxetane intermediate
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Investigation of the stereoselectivity of the
Mn(III)salen catalysed epoxidation reaction
mechanism by DFT
Highly enantioselective!!! What is its origin???

• How can the relatively flat catalyst give such
  impressive
• selectivity?
• (2) What is the trajectory of approach of alkenes
  (top, side, or
• bottom on 1) to the MnO intermediate?
• (3) What is the timing of bond formation between
  the alkene
• and transferred oxygen?

The above issues can be explored in more details
by computing the geometries of the
manganese-Oxo intermediate as a prelude to
transition state searches.
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Computational details
Program Gaussian-94 TheoryDFT FunctionalB3LYP B
asis set Split valence double ? (DZ) basis set
3-21G Double ? plus polarisation basis set
6-31G DZ and TZ valence basis set for Mn
(C, H, Cl, N,O)
Org. Lett., Vol. 1, No. 3, 1999
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Model systems employed in calculation
2-Mn(V)
1 - Mn(III)
3 -Mn(III)
4-Mn(V)
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Spin multiplicity
Mn(0) 3d7
Oxidation state range II to VII
Mn(III) d4 (Oh)
Low spin singlet (S0)
Intermediate spin Triplet (S1)
High spin Quintet (S2)
Mn(III) d4 (Oh)
Mn(V) d2(Oh)
Quintet (S2)
Singlet (S1)
Triplet (S1
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Quintet and triplet state geometries of the
Manganese(III) model systems
1 H.S (q)
1 L.S (t)
3 H.S (t)
3 H.S (q)
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Manganese(V) model compounds calculated by
the manganese triple-? basis/Becke3LYP/6-31G
2 (s) 0 kcal/mol
2 (q) 11.2 kcal/mol
2(t) 3.5 kcal/mol
4 (q) 2.0 kcal/mol
4 (s) 10.2 kcal/mol
4 (t) 0 kcal/mol
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Comparison of X-ray data to calculated values
for model systems
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Becke3LYP/3-21G relative energies (kcal/mol) for
model systems 1-4
The ltS2gt values measure whether the spin state is
pure singlet, triplet or quintet (S2 0, 2, 6,
resp)
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Becke3LYP/6-31G (CHClNO)/DZ (Mn) relative
energies (kcal/mol) for model systems 1-4
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Becke3LYP/6-31G (CHClNO)/TZ (Mn) Relative
energies (kcal/mol) for model systems 1-4

• The Mn(III) catalysts are predicted to be high
  spin (i.e Quintet)
• The ligand field does not split the degeneracy
  of the d orbitals significantly - No spin pairing
• Mn(V)Oxo is predicted to have nearly degenerate
  singlet and
• triplet states.

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Conclusion

• A low spin ( s or t) complex is favoured with
  weak coordination or
• absence of a 6th ligand
• A high spin (t or q) state occurs upon
  association of a stronger
• ligand.
• High spin oxo intermediate could lead directly
  to high spin product
• in a concerted fashion with conservation of
  spin.
• Low spin species would have to undergo a change
  of spin
• multiplicity during reaction which could give
  stepwise processes.
• Nature of the ligand will influence spin
  multiplicities and
• potentially the relative rates of stereo
  specific concerted and
• stepwise nonconcerted processes.

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Investigation of the origin of enantioselectivity
in the epoxidation of alkenes catalysed by
anchored oxo Mn(V)-salen into MCM-41 channels
DFT and QM/MM approach
Journal of molecular catalysis A Chemical
271(2007) 98-104
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Objective

• Based on DFT and QM/MM calculations,
• To rationalise the effect of immobilization and
  show how that
• correlates with the linker and substrate
  choices.
• To evaluate the enantioselectivity of the
  catalyst with respect to the
• energy surfaces along the epoxidation
  reaction pathway.

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Model systems employed in calculation
I
II
The full (I) and truncated (II) models of the
Mn-salen complex
L(axial linker) Cl-, Phenoxyl
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Model systems employed in calculation
(b) The model for the immobilized Mn-salen
complexes using phenoxyl axial linkage.

• Visualized Mn-salen complexes
• anchored inside a MCM-41 channel
• using phenoxyl group as the
• immobilizing linker

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Relative energies of spin states for oxo-Mn-salen
II complex vs. axial linkage (Calculated by
Mn(tz) basis using B3LYP/6-31G functional)

• The triplet state is found to be the ground state
  for both Cl- and
• phenoxyl linkers.
• Epoxidation reaction for both homogeneous
  catalyst (i.e., Cl- is
• the axial ligand) and heterogeneous catalysts
  (i.e., phenoxyl group
• is the axial ligand) occurs on a triplet
  surface.

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Effect of axial linkage on the geometry of
oxo-Mn-salen II for the triplet spin sate using
B3LYP method distances in A , angles in degrees
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DFT-calculated structures for the truncated
Oxo-Mn-salen II with Cl-
Optimised structure
HOMO
LUMO
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Optimized geometry of TS1 and TS2 corresponding
to the attack of TBMS for homogeneous Mn-salen
catalyst
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General mechanism scheme for asymmetric
epoxidation of olefins using Mn-salen complexes,
L axial linker
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Reaction profiles for the oxygen transfer
reaction on the triplet surface for homogeneous
Mn-salen catalyst
1. It is the mixture of CBMS and the catalyst in
gas phase without any interaction in
between. 2.Olefin enters the coordination sphere
of complex from the MnO center. Activation
energy for TS122 kJmol 3. Formation of radical
intermediate.(90 kJ/mol more stable than
2) Activation energy for TS235
kJ/mol 4.Formation of Epoxide complex.
Trans-?-methyl styrene (TBMS)
Cis-?-methyl styrene (CBMS)
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Results of DFT calculation

• The attack of TBMS is overall about 7 kJ/mol
  less in favour
• compared to that in CBMS.
• The epoxide complex formed by TBMS lies 2.5
  kJ/mol below
• the epoxide complex formed by CBMS.
• These findings are in agreement with a general
  assumption in
• homogeneous Mn-salen catalyst that TBMS is a
  less suitable
• substrate than CBMS.
• The more stable t rans-epoxide complex 4 is in
  qualitative
• agreement with the experimental observation that
  epoxidation of
• CBMS leads to a thermodynamically more stable
  trans-epoxide

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DFT-calculated structures for the truncated
oxo-Mn(II)salen with phenoxyl, located trans- to
the oxo group
HOMO
LUMO
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Optimised geometry of the transition states TS1
and TS2 corresponding to the attack of TBMS at
the MnO center of heterogeneous Mn-salen catalyst
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Energy profile for the epoxidation reaction of
CBMS and TBMS catalyzed by immobilized Mn-salen
complex.
TBMS
CBMS
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Result DFT calculation for the attack of CBMS

• The activation barrier for the formation of
  adsorbed CBMS radical is overall
• 8 kJ/mol less than that for the homogeneous
  salen catalyst.
• (Homogeneous catalyst 22 kJ/mol heterogeneous
  catalyst14 kJ/mol)
• The activation energy for epoxide complex
  formation is about 5 kJ/mol
• lowered for the immobilized Mn-salen complex
  than that for the homogeneous
• salen catalyst.
• (Homogeneous catalyst35 kJ/mol heterogeneous
  catalyst30 kJ/mol)
• On the triplet energy surface, the calculations
  suggest that epoxide formation
• is clearly more preferred by the immobilized
  catalyst compared to the
• homogeneous catalyst.
• These observations provide an explanation for the
  effectiveness and
• importance of additional ligand as the
  immobilizing linker.

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DFT calculation for the attack of TBMS

• In contrast to the homogeneous epoxidation
  reaction, a trans olefin
• can be a suitable substrate for epoxidation by
  immobilized Mn-salen catalysts.
• Epoxide complex 4 formed of CBMS is slightly (3
  kJ/mol) more stable than its
• trans-epoxide counterpart, despite of the fact
  that there is a lower barrier
• (5 kJ/mol) towards epoxide formation starting
  from TBMS radical adsorbed
• on MnO center.
• The energy profile strongly depends on electron
  donor/acceptor properties of the
• axial linker.

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Modelling of MCM-41 silica channel

• MCM-41 silica channel was modelled based on a
  straight, three-dimensional channel.

Pore length 3.4 nm

• The structure was represented by the pseudo cell,
  Si6O12, consists of hexagon arrangements of
  SiOSi units.
• Oxygen atoms saturate all silicon atoms at the
  pore surface.
• Oxygen atoms with fewer than two silicon atoms
  attached to them (at the inlet, outlet and outer
  surface) were then saturated by hydrogen atoms.
  

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Modelling of MCM-41 silica channel

• This model places the silicon and oxygen atoms in
  a simple geometrical arrangement and does not
  reproduce the real amorphous structure of
  MCM-41.
• In this MCM-41 model, all hydroxyl groups were
  located at the outer surface.
• The pore length is 3.4 nm and the pore diameter
  is 2.3 nm.
• Immobilization was performed by attaching the Si
  atom of the linker to oxygen atoms connected to
  two Si atoms on the wall (SiLinkerOSiMCM).

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Model used for ONIUM based QM/MM calculation

• A two-layer ONIOM protocol was used to couple
  the QM and MM parts in the full Mn-salen-L (L
  pheoxyl) calculations as well as for the
  immobilized Mn-salen catalyst into MCM-41
  channel.
• The high-level model system includes Mn, N, O,
  carbon atoms at the bridge and the full substrate
  and linker atoms.
• The low level calculation includes the rest of
  salen ligand and the atoms of MCM-41 channel.

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Reaction profiles for the epoxidation of CBMS on
the triplet surface for Mn-salen immobilized into
MCM-41 channel using a phenoxyl linker

• Energy barrier are lower because of the
  confinement effect inside MCM-41 channel.
• The more restricted space inside the mesopore in
  combination with the effect of immobilizing
  linker hinders the free-movement of the attached
  olefin.
• Besides, a full-salen ligand with substituents
  at 5, 5- and 3, 3-positions exhibits stronger
  steric influences compared to that for the model
  complex II.

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Conclusions
Catalyst Suitable substrate
Main product Homogeneous
cis-olefin trans-epoxide
Heterogeneous Trans-olefin
cis-epoxide

• Comparison of the optimized structure of the
  intermediate oxo-Mn-salen with the
• chloride and phenoxyl linker at the
  trans-position leads to the following
• suggestions
• Any coordination in the trans-position causes the
  Mn atom to move into the plane
• of the ligand.
• The movement of the Mn atom can improve the
  enantioselectivity in view of the
• shielding of the oxygen by the equatorial
  ligands.
• The MnO bond becomes lengthened facilitates
  oxygen transfer to the olefin.
• A trans-substrate has a higher level of
  asymmetric induction to the immobilized
• Mn-salen complex than that to a homogeneous
  catalyst, but the reaction path is
• more in favor of the cis-substrate.
• The MCM-41 channel reduces the energy barriers
  and enhances the
• enantioselectivity by influencing geometrical
  distortions of the Mn-salen
• complex.

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Thank U
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Questions?
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