I. Modeling the Reaction between I. Modeling the Reaction between Vinylamine and Singlet OxygenVinylamine and Singlet Oxygen

A Semi-Empirical Molecular Orbital Computational Study

Singlet OxygenSinglet Oxygen

Singlet oxygen (1O2) is an electronically excited form of molecular oxygen.

It is short-lived (~10-5 s), but very reactive.

Usually generated by dye-sensitization:

1Dye ____h____> 1Dye* 1Dye* ____(isc)____> 3Dye*

3Dye* + 3O2 __________> 1O2 + 1Dye

Electron Configuration of Electron Configuration of Singlet Oxygen (HOMO)Singlet Oxygen (HOMO)

3g 1g 1g

(ground state) 22 kcal/mol 37.5 kcal/mol

Triplet Singlet

Typical Modes of Reaction of Typical Modes of Reaction of Singlet OxygenSinglet Oxygen

1O2O

O+

1O2+O OH

X 1O2+

X

OO dioxetane

ene type product

endoperoxide

Reaction of Reaction of 11OO22 with Enamines with Enamines

NH2 1O2+

NH

CCH O

H

+ H2O

Based on product studies in more complex enamines (vinylamine is unstable and very difficult to prepare; it is modeled because it is small, and amenable to rapid calculation):

Modeling Singlet OxygenModeling Singlet Oxygen

Calculated Hf in kcal/mol

Structure MNDO AM1 MINDO/3

singlet O2 12.2 0.7 22.8

(Experimental value is 22.5 kcal/mol)

Intermediates Proposed for Intermediates Proposed for Reaction of Singlet Oxygen Reaction of Singlet Oxygen with Enamineswith Enamines

O

O NH2

O ONH2

OO

NH

OHO

NH2

OO

NH2

O

O

NH2

BackgroundBackground

We had strong kinetic (substituent effect) evidence that favored rate-limiting formation of a charge-transfer complex in the photo-oxygenation (reaction with singlet oxygen) of 1-benzyl-3,4-dihydroisoquinolines, which are in equilibrium with an enamine tautomer.

We decided to model a similar mechanism for vinylamine, the simplest enamine.

Modeling an InteractionModeling an Interaction

An AMPAC input file was created by merging two independently optimized structures: vinylamine and singlet oxygen

Various orientations were tried When one geometry showed

attractive interaction, it was examined more closely.

NCH2C

HH

H

O O

Optimizing the GeometryOptimizing the Geometry

The N-O ‘bond’ length was varied The N-O-O bond angle was varied The C-N-O-O dihedral angle was varied After optimizing one variable,

it was fixed to optimize another; then two were fixed to optimize the third.

Finally the structure was allowed to optimize starting with the best values of the three variables.

NCH2C

HH

H

O O

Attraction between Singlet Attraction between Singlet Oxygen and VinylamineOxygen and Vinylamine

Proposed Orbital InteractionProposed Orbital Interaction

N

O O (LUMO)

2p (HOMO)

Optimized Geometry of the Optimized Geometry of the Charge-Transfer ComplexCharge-Transfer Complex

NCH2C

HH

H

O O

An energy minimum was found at an N-O “bond” length of 1.55 Ao

The lowest energy complex was found to have an N-O-O “bond” angle of 111o

The lowest energy complex was found to have a C-N-O-O dihedral angle of 139o

Reaction Pathway Calculation:Reaction Pathway Calculation:Input File to Vary Bond LengthInput File to Vary Bond Length

t=5000 MINDO3

vinylamine

7 0.00000 0 0.0000 0 0.0000 0 0 0 0

6 1.38210 1 0.0000 0 0.0000 0 1 0 0

1 1.09000 1 113.9000 1 0.0000 1 2 1 0

6 1.34000 1 124.8000 1 179.9000 1 2 1 3

1 0.99900 1 122.4000 0 179.9000 1 1 2 3

1 0.99900 1 120.8000 1 0.0000 1 1 2 3

1 1.08000 1 124.7000 1 0.0000 1 4 2 1

1 1.08000 1 121.3000 1 179.9000 1 4 2 1

8 1.55000 -1 111.4000 1 137.1000 1 1 2 4

8 1.13000 1 111.1000 1 138.9000 1 9 1 2

0 0.00000 0 0.0000 0 0.0000 0 0 0 0

1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9, 2, 2.2, 2.4, 2.6, 3, 4, 6, 8, 10

Locating the Transition Locating the Transition StructureStructure

The keywords SADDLE, POWELL, and SIGMA were employed sequentially with the geometry of the reactant, a “guess” at the T.S. geometry, and the product geometry.

A FORCE calculation was done on the T.S. geometry provided by this method.

This yielded only 1 imaginary (negative) frequency, confirming the saddle point.

Reaction Energy Profiles: Reaction Energy Profiles: Zwitterionic Peroxide (a) and CT Complex Zwitterionic Peroxide (a) and CT Complex followed by Zwitterionic Peroxide (b)followed by Zwitterionic Peroxide (b)

ConclusionConclusion

A charge-transfer complex may be competitive with direct zwitterionic peroxide formation in the reaction of singlet oxygen with enamines, particularly in those cases where more complex structures may stabilize the intermediate complex or facilitate its rearrangement.

II. Modeling the Quenching of II. Modeling the Quenching of Singlet Oxygen by AminesSinglet Oxygen by Amines

A Semi-Empirical Molecular Orbital Computational Study

Singlet OxygenSinglet Oxygen

Singlet oxygen (1O2) is an electronically excited form of molecular oxygen.

It is short-lived (~10-6 s), but very reactive.

Usually generated by dye-sensitization:

1Dye ____h____> 1Dye* 1Dye* ____(isc)____> 3Dye*

3Dye* + 3O2 __________> 1O2 + 1Dye

Singlet Oxygen...Singlet Oxygen... It is quenched efficiently by tertiary amines, especially DABCO (diazabicyclooctane):

DABCO is sterically unhindered, unlike most tertiary amines, and has a low IP...therefore it

should be a good electron donor.NN

Quenching of Singlet Oxygen Quenching of Singlet Oxygen by Aminesby Amines

Ionization Energy vs Log Kq

5

5.5

6

6.5

7

7.5

8

7.5 8 8.5 9 9.5

Ionization Energy

Lo

g K

q

QuenchingQuenching

No chemical reaction involved...amines are unchanged

Physical quenching…rate related inversely to ionization potential of the amine

Very sensitive to steric effects in the vicinity of nitrogen

This data suggests a charge-transfer mechanism.

Proposed Orbital InteractionProposed Orbital Interaction (same as for C.T. complex formation)(same as for C.T. complex formation)

N

O O (LUMO)

2p (HOMO)

Our Approach:Our Approach:

Model various amines and singlet oxygen (optimized separately) in proximity to one another and look for an interaction (attraction); AMPAC/MINDO3 was used.

When an attraction is observed, examine the complex more closely to determine the optimum geometry.

Use knowledge gained from geometry of vinylamine-singlet oxygen complex.

Determining the Optimum Determining the Optimum N-O ‘Bond’ Distance N-O ‘Bond’ Distance

-0.5

0

0.5

1

1.5

2

2.5

3

1.45 1.5 1.55 1.6 1.65N-O DISTANCE

RE

LA

TIV

E E

NE

RG

Y

Determining the Optimum Determining the Optimum N-O-O ‘Bond’ Angle N-O-O ‘Bond’ Angle

-0.5

0

0.5

1

1.5

2

114 116 118 120 122

BOND ANGLE

RE

LA

TIV

E E

NE

RG

Y

Determining the Optimum Determining the Optimum N-O-O-O Dihedral Angle N-O-O-O Dihedral Angle

-0.5

0

0.5

1

1.5

2

2.5

3

160 170 180 190 200DIHEDRAL ANGLE

RE

LA

TIV

E E

NE

RG

Y

Typical Optimum Geometry of Typical Optimum Geometry of Amine-Amine-11OO22 Complexes Complexes

N-O ‘bond’ length of 1.55 Ao

N-O-O bond angle of 119o

C-N-O-O dihedral angle of 180o

Transfer of ~0.3 esu of charge from N to distal O is observed (more than in vinylamine).

Modeling Charge-Transfer Modeling Charge-Transfer Complexation of Amines Complexation of Amines with Singlet Oxygenwith Singlet Oxygen

N-O “bond” distance = 1.55 Ao

qN = +0.35esu qOdistal = -0.33 esu

Unexpected Results!Unexpected Results!

0

5

10

15

20

25

02468

N-O Separation, Angstroms

En

tha

lpy

of

Fo

rma

tio

n,

kc

al/

mo

l

Primary

Secondary

Tertiary

An Alternative Hypothesis:An Alternative Hypothesis:

Perhaps rate-limiting step is NOT formation of the

charge-transfer complex, but instead is intersystem

crossing (ISC) to the triplet complex:

[ 1O2 . . . 1NR3 ]

___ISC___> [ 3O2 . . . 3NR3 ]

This process can not be modeled, but can be

estimated by single point calculations.

Considering Triplet ComplexConsidering Triplet Complex

-24

-16

-8

0

8

16

24

32

40

48

-8 -6 -4 -2 0 2 4 6 8

N-O Separation, Angstroms

Rela

tive E

nth

alp

y o

f F

orm

ation,

kcal/m

ol

Triplet with

Singlet geometry

Singlet Triplet

Consistent with Slow ISC !Consistent with Slow ISC !

4.5

5

5.5

6

6.5

7

7.5

15 25 35 45

Enthalpy of Activation forIntersystem Crossing

Log

kq r = - 0.97

Acknowledgments: Financial Acknowledgments: Financial and Technical Supportand Technical Support

UNCW Office of Information Technology for use of the VAX computer

M.J.S. Dewar (now deceased) and Eamon F. Healy for providing a free copy of AMPAC

NSF for an ILI grant (1996) to Integrate Molecular Modeling into the Chemistry Curriculum (computers and software)

Acknowledgments: Acknowledgments: The WorkersThe Workers

Reaction of Singlet Oxygen with Vinylamine: David B. Allen and Kelly N. Taylor

Quenching of Singlet Oxygen by Amines: Charles K. Marschke, Jr., Chris A. Cottle and Noah W. Allen, III.