Structural Characterization and Electronic Properties of a Cyclic Non-heme-iron-dinitrosyl Complex: [Fe(NO) 2 Imidazole] 4 Eric Sundberg and Lijuan Li.

N N

HC

HC

NCH HC N

CH

HC

Fe

N

HC

CH

N

CH

Fe

Fe

NHC

NCH

CH

N

N

NN

N

N

NN

O O

O

O

OO

O

O

Structural Characterization and Electronic Properties of a Cyclic

Non-heme-iron-dinitrosyl Complex: [Fe(NO)2Imidazole]4

Structural Characterization and Electronic Properties of a Cyclic

Non-heme-iron-dinitrosyl Complex: [Fe(NO)2Imidazole]4

Eric Sundberg and Lijuan Li

California State University, Long Beach

Eric Sundberg and Lijuan Li

California State University, Long Beach

Nitric Oxide ChemistryNitric Oxide Chemistry• 30 Years ago:

– A major contributor to smog– An ingredient in cigarette smoke and automobile exhaust – A suspected carcinogen– An ozone depleting agent– Toxic, noxious chemical

Koshland, D. E., Jr. Science 1992, 258, 1861-1902

Nitric Oxide ChemistryNitric Oxide Chemistry

• In 1992, it was named the “Molecule of the Year” by the journal Science in an article titled, “NO News is Good News”

• In 1998 three gentlemen were awarded the nobel prize in medicine and physiology for their work involving the biological aspects of nitric oxide

Nitric Oxide ChemistryNitric Oxide Chemistry

Furchgott Ignarro MuradDiscovered that nitric oxide works as a signaling

molecule in the cardiovascular systemDiscovered that nitric oxide works as a signaling

molecule in the cardiovascular system

http://www.nobel.se/medicine/laureates/1998/index.html

Nitric Oxide ChemistryNitric Oxide Chemistry

• Maintains blood Maintains blood pressure by dilating pressure by dilating blood vesselsblood vessels

• Kills foreign invadersKills foreign invaders• Involved in Involved in

neurotransmissionneurotransmission

• Maintains blood Maintains blood pressure by dilating pressure by dilating blood vesselsblood vessels

• Kills foreign invadersKills foreign invaders• Involved in Involved in

neurotransmissionneurotransmission

• Involved in learning Involved in learning and memory processesand memory processes

• Controls platelet Controls platelet aggregationaggregation

• Stimulates penile Stimulates penile erectionserections

• Involved in learning Involved in learning and memory processesand memory processes

• Controls platelet Controls platelet aggregationaggregation

• Stimulates penile Stimulates penile erectionserections

Numerous Physiological Functions

Feldman, P. L.; Griffith, O. W.; Stuehr, D. J. Chem Eng. News 1993, 71 (Dec), 26-38

Heme Versus Non-hemeHeme Versus Non-heme• Nitrosyl (NO) on a

hemoglobin molecule• Nitrosyl attached to a

non-heme molecule• Nitrosyl attached to a

non-heme molecule

Fe

N

N

N

N

CH3

CH3CH3

CH3

COOH COOH

NO

Fe

NO

Fe

NO

NO

L

L

+ NO

Muller, B.; kleschyov, A. L.; Stoclet, J. C. Br. J. Pharm. 1996, 119, 1281-1285

Density Functional Theory

Stability UV-vis

Electrochemistry

EPR and NMR

ClassificationSynthesis

OutlineOutlineNon-heme iron Dinitroyls

Characterization

FT-IR X-ray Crystallography

SynthesisSynthesis

Fe(CO)2(NO)2 + C3H4N2

C

NN

C

O

Fe

O

O O

Starting Material:Dicarbonyldinitrosyliron(0)

N

NH

Ligand: Imidazole

SynthesisSynthesis• After 2 Hours: • After 24 Hours:

N

HN

N N

O O

Fe

C

O

N N

HC

HC

NCH HC N

CH

HC

Fe

N

HC

CH

N

CH

Fe

Fe

NHC

NCH

CH

N

N

NN

N

N

NN

O O

O

O

OO

O

O

1757.5

7

1806.8

3

2031.6

9

2088.0

1Fe(CO)2(NO)2

60

80

100

%T

1686.6

3

1731.0

1

1982.5

0

Fe(CO)(NO)2(Im)

20

40

60

80

%T

1725.9

5

1796.7

8

Fe(NO)2(Im)2

10

15

20

%T

1600 1800 2000 2200 2400 2600

Wavenumbers (cm-1)

CharacterizationCharacterization

N

HN

N N

O O

Fe

C

O

C

NN

C

O

Fe

O

O O

CharacterizationCharacterization

• X-ray Crystallography shows a cyclic compound with an acetone molecule trapped inside

Materials and MethodsMaterials and Methods

• Recrystallized [Fe(NO)2Im]4

• Nuclear Magnetic Resonance– Dissolved 50mg of sample into 2 mls of deuterated

THF and transferred to a NMR tube

– AC200 Spectrometer

• Electron Paramagnetic Resonance– Dissolved 2 mg of sample into degassed 1 ml of THF

and transferred to EPR tube

– Brooker EMX Model EPR Spectrometer

Materials and MethodsMaterials and Methods• Electrochemistry

– 3 electrode system with a gold working electrode

– THF was used as the solvent– Scan Rate of 100 mV sec-1

– 10mM [Fe(NO)2(Imidazole)]4 solution and a 0.1M electrolyte solution, (tetrabutylammonium perchlorate)

– Computer Controlled Electrochemical Analyzer

Autolab Electrochemical Insturments

http://www.ecochemie.nl/

Materials and MethodsMaterials and Methods

• UV-vis Spectroscopy– Varian 300 Bio UV-vis spectrophotometer– Dilution Series in THF: 0.1-0.8 mM

Cary Uv-vis Spectrometer

www.varianinc.com

Materials and MethodsMaterials and Methods

• Stability– FT-IR spectroscopy (Nicholet 380

Spectrometer) – 0.2mM in THF at 15 and 30 minutes

• Spin Density Functional Theory– Performed using X-ray crystallographic

coordinates– Dr. Fu-Ming Tao at Cal. State Univ. Fullerton

Nuclear Magnetic ResonanceNuclear Magnetic Resonance

ppm9.0 01.02.03.04.05.06.07.08.0

1H NMR

(H1)

(H2&H3)

H2&H3

H1

Nuclear Magnetic ResonanceNuclear Magnetic Resonance

306090120150180210240

ppm

13C NMR

C2&C3

C1

C1

C2&C3

Electron Paramagnetic ResonanceElectron Paramagnetic ResonanceElectron Paramagnetic ResonanceElectron Paramagnetic Resonance

g=2.03

20G

Hyperfine Structure

ElectrochemistryElectrochemistry

UV-vis SpectroscopyUV-vis Spectroscopy

MLCT

d-d transitions

Stability under Oxygen

1725.9

5

1796.7

8

Fe(NO)2(Im)2

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

%T

ransm

ittance

1200 1400 1600 1800 2000 2200 2400 2600 2800 3000 3200 3400

Wavenumbers (cm-1)

Spin Density Functional Calculations

• Will provide wavefunction analysis of the molecule = a + b + c…– A diagram of the electron density on the

molecule

1757.5

7

1806.8

3

2031.6

9

2088.0

1Fe(CO)2(NO)2

60

80

100

%T

1686.6

3

1731.0

1

1982.5

0

Fe(CO)(NO)2(Im)

20

40

60

80

%T

1725.9

5

1796.7

8

Fe(NO)2(Im)2

10

15

20

%T

1600 1800 2000 2200 2400 2600

Wavenumbers (cm-1)

Spin Density Functional Calculations

N

HN

N N

O O

Fe

C

O

C

NN

C

O

Fe

O

O O

Spin Density Functional CalculationsSpin Density Functional Calculations

Fe ON:NNH

:

:NN

: N OFe +

Fe

Single- Substituted Product

Cyclic Product

ConclusionConclusion• [Fe(NO)2Im]4 has been characterized by

– X-ray Crystallography and FT-IR Spectroscopy– NMR and EPR techniques

• Electrochemistry showed 2 chemically reversible reductions

• UV-vis spectroscopy showed MLCT and d-d orbital transitions

ConclusionConclusion

• Low stability of compound in solution when exposed to oxygen

• Spin Density Functional Theory showed excess electronic density on the imidazole

• Potential Medicinal Applications

Future StudiesFuture Studies

• Mass spectrometry

• Elemental analysis

• NMR studies of decomposed sample

• Laser flash photolysis

AcknowledgementsAcknowledgements

• Dr. Lijuan Li

• Dr. Ximeng Wang

• The Beckman Scholars Foundation

• Howard Huges Medical Institute