Lab F

A Comprehensive Investigation of Phthalocyanine Metal Cation

Complexes

J. Canino, J. Head, J. Kasparian,

G. Lincourt, A. Mc Cusker, A. Mills, J. Prata

University of Rhode IslandCHM402 Spring 2007

Outline

• Introduction and History• Current Applications• Synthesis and Analysis Overview• IR Analysis• EPR Analysis• UV-Vis Analysis• Conclusion and Future Applications• Acknowledgements

Phthalocyanines are extremely stable planar molecules with Cs symmetry

They have an 18π-electron heterocyclic aromatic system

Introduction

N

N

NH

N

NH

N

N

N

Introduction

• Phthalocyanines are a derivative of porphyrins• A porphyrin is a heterocyclic macrocycle derived

from four pyrrole-like subunits interconnected via methine (=CH-) bridges connecting their α carbon atoms.

N

N

NH

N

NH

N

N

N

Introduction

• Porphyrins are naturally occurring products.• They can be found in many of our own body’s synthesis.• Protoporphyrin IX is formed from Protoporphyrinogen

oxidase and then Ferrochelatase converts it to Heme, which is a critical metalloprotein in the body.

Protoporphyrin IXHeme

Introduction

• Phthalocyanines are the result

of the reaction of phthalanonitrile

with metals or metal salts at

elevated temperatures.

• A typical reaction of the development of phthalocyanines can be seen in the formation of copper phthalocyanine.

CN

CN

phthalanonitrile

Introduction

Copper Phthalocyanine is the most stable of the phthalocyanines and potentially the most stable

organic compound ever.

N

N

N

N

N

N

N

N

CuCN

CN+ Cu

2+

4

History

• The word phthalocyanine is derived from the Greek words for naphtha, meaning rock oil and cyanine, meaning blue

• This term was first used by Sir Patrick Linstead in 1933 to describe a new class of organic compounds.

• Phthalocyanine itself, however, is believed to have been discovered in 1907 as an accidental by-product of the synthesis of o-cyanobenzamide

History

• The development of phthalocyanine started in 1928 at Scotland Dyes Works

• The workers using phthalimide found it to be contaminated with a dark colored impurity

• They called in their scientists to isolate the product and determine its nature.

History

• They collected samples of the impurity but it was still mixed with the phthalimide.

• They found that treating the impurity with boiling water separated the two compounds.

• Phthalimide dissolved in the water but the impurity remained in its solid form. Simple filtration separated the two.

History

• With further investigation it was found that the impurity was extremely resistant to both heat and most reagents.

• Phthalimide was made from phthalic anhydride and ammonia in a large enamel coated iron drum

• They found some small chips in the enamel of the drum leading them to believe that some iron had gotten into the phthalimide and created the impurity.

History

• They determined that Iron was the source of the dark color and they set out to remove the iron.

• They tried boiling it with hydrochloric acid and testing for it in filtered liquid and testing it with ammonium thiocyanate.

• Iron was not removable by these means.

History

• The problem was sent to Royal College of Science where attempts were made to dissolve iron compound in concentrated sulphuric acid.

• Concentrated nitric acid removed color and turned substance into white precipitate when poured into ice-coldwater. Isolation and examination

revealed that it consisted of pthalimide.

NH

O

O

History

• When cuprous chloride was added to molten phthalimide, there was a vigorous reaction with the formulation of a colored product.

• They determined that the metals had to be a key part of the structure of this new compound.

• With this new element in the mix, J. Monteath Robertson at the Royal College of Science set out to discover the structure of the molecule.

History

• First he determined the empirical formula using micro-combustion techniques.

• Once he had the empirical formula the molecular weight was also determined.

History

• Using the molecular weight and knowing that the product must have an isoindole skeleton similar to phthalimide, he deduced the structure.

• This structure was later confirmed by x-ray contour diagrams.

NH

Isoindole

N

N

NH

N

NH

N

N

N

phthalocyanine

Current Applications Copper Dyes

Desirable Properties of Phthalocyanine Blue BN

• Light fastness• Tinting strength• Covering power• Resistance to the

effects of alkalies and acids

Current Applications Copper Dyes

Common Uses of Phthalocyanine Blue BN

• Paints• Inks • Coatings• Many plastics

Current Applications Copper Dyes

• Phthalocyanine Green G is simply chlorinated CuPC• Addition of chlorine shifts the absorption spectrum• Also used in tattoos and cosmetics

Current Applications CD-R Dyes

• Usually silver, gold or light green

• Rated lifetime of hundreds of years

• Phthalocyanine is resistant to UV rays

• Degradation only after two weeks of direct sunlight exposure.

Current Applications Electrochemistry

• Phthalocyanine possesses electronic conductivity due to lengthy conjugated system and pi-stacking.

NH

N

N

N

N

N

HN

N

Current Applications Electrochemistry

• Phthalocyanines are good semiconductors with characteristically low impedance

• Dilithium phthalocyanines have mixed electronic and ionic conducting properties due to the high mobility of the metal in the electron channels produced by pi-stacking

• Electronic conductivity increases with use of DC over AC

Current Applications Thin Film Transistors

• Type of field effect transistor• Used in flat screen technology• Comprised of layers of metallic contacts,

semiconductive material, and a dielectric layer• Semiconductive material must be transparent• Qualities desired include high mobility, low leak

currents, and threshold voltages

Current Applications Thin Film Transistors

• Separates pixels on a screen to afford greater clarity

• LCD Screen technology

• Found in most cell phones

Current Applications Thin Film Transistors

• Active layer is an ordered film of a phthalocyanine coordination compound

• Field-effect mobility greater than 10-3 cm2 /Vs• Conductivity in the range of about 10-9 S/cm to

about 10-7 S/cm at 20° C• Copper phthalocyanine, zinc phthalocyanine,

hydrogen phthalocyanine, and tin phthalocyanine

Current Applications Catalysis

• H2/O2 cells• Large energy payoff• Alternative Fuel• Requires the 2e-

reduction of oxygen – a process which requires a large energy input

• Possible solution: Organic Catalysis

Current Applications Catalysis

• Fe and Co phthalocyanines

• Catalysts for the electroreduction of oxygen

• Cheaper replacement for Pt

• The potential of an electrode containing 30% catalyst is 100 mV more positive than that of an electrode with 13% platinum

• Cells still have H2O2 as byproducts

Synthesis of PhthalocyanineProcedure

• Obtain 1mmol of the metal chloride or chloride hydrate salt

•Flame-dry flask if the metal is hydrated

•Add 3 mmol of phthalonitrile and 3mL of N,N-dimethylethanolamine.

•Add a dry reflux condenser containing a drying tube at the top and bring the contents to reflux in a sand bath.

•Reflux until the solution turns deep blue, then allow it to cool to RT. Filter first with 10mL of water and then 10mL of methanol.

Synthesis of PhthalocyanineReaction

CN

CN

CoCl2 + 4

D M A E

h e a t ~ 1 3 5 °C + 2Cl-

18 -electron aromatic macrocycle

Pc can host over 70 different metal ions in its central cavity

Metals included in this experiment:

Ni Co Mg

Cu Li

Zn Mn

Challenges in Synthesis

The central metal is used as a template, activating the bonding of the Phthalonitrile.

For efficient synthesis, the central metal must be a particular size. If too large a metal is introduced, the synthesis may not take place. A metal that is too small may fall out of the central hole.

2

Compound Percent Yield Ionic Radii (pm) (4)Ni 60.8% 69 pmCu 71.4% 71 pmZn 53.0% 75 pmCo 90.0% 72 pm (high-spin)Li 30.0% 41 pm (approx.)

Mn 65.0% 81 pm (approx.)

Large-Scale Synthesis

The first phthalocyanine to be manufactured commercially was copper phthalocyanine. It was made in 1934, in England. A similar product was synthesized in the United States in 1937 by Du Pont.

Traditional Synthesis Methods:

Heating the phthalonitrile to 350-360ºC for 7 hours in a sealed tube, or heating the phthalonitrile to 170-180ºC in triethanolamine for 4 hours.

Simply adding 4 moles of phthalonitrile to 1 mole of metal salt at 220-250ºC for 2-6 hours. This procedure would result in a 70-77 percent yield of PC on a plant scale.

Large-Scale Synthesis

Phthalonitrile Processes for industrial yields (90-93% based on phthalonitrile consumed):

•A closed system is charged with reactants and heated to 140ºC under 5atm. Air was partially removed. An exothermic reaction takes place, and the system achieves a temperature of 300ºC. The product was allowed to cool overnight.

•Processes done in solution used phthalonitrile, pyridine, and either nitrobenzene, trichlorobenzene, or monochlorobenzene under pressure. These processes achieved similar yields.

Summary

The ideal size for the central metal of the Pc is in the low 70pm ionic radius range.

• Heating the solution for a greater amount of time may have significantly increased the yields of the products.

Improvements:

• Running the reaction under an inert gas such as nitrogen or under vacuum may have helped the reaction.

Analysis:To determine if the desired product was created, an IR, UV-Vis, and EPR was run on each metal Pc.

Analysis:IR Spectroscopy

IR region measures the spectrum between the visible and microwave regions. Practical use ranges from 400-

4000cm-1

•Asymmetrical C-N=C vibration at 1486cm-1

•C-N bending at 1000-1250cm-1

•C-H stretching 2850-3000cm-1

•In substituted Pc’s, a strong absorption between 1430-1470cm-1 occurs with increases in alkyl chain length. This is related to the vibration mode of CH2 and CH3 groups.

•Small peaks in the 740-900cm-1 range is attributed to the breathing modes of the Pc.

AnalysisUV-Vis Spectroscopy

UV-Vis Spectral range is from 525nm-750nm and it is identify electronic transitions in molecules.

Types of Electronic Transitions:

Transition Molar absorption coefficient

Charge-Transfer 1000-10000 L/mol-cm

d-d spin-allowed < 10L/mol-cm for Oh or up to 100 L/mol-cm for nearly Oh complexes

d-d spin-forbidden < 1L/mol-cm

Transitions can be metal-to-ligand (MLCT) or ligand-to-metal (LMCT). MLCT are much more common.

Analysis:Electron Paramagnetic

Resonance Spectroscopy (EPR)

• Method of analysis is to follow the energy change as unpaired electrons flip in a magnetic field B0.

• Microwave radiation is constantly introduced to the sample and transitions are seen as absorption at a frequency υ

E = h υ = gμBB0

μB is the Bohr Magneton 9.27401 x 10-24 J T-1

The g value for a free electron is 2.0023, but the value can differ as a result of spin-orbit coupling.

Analysis:Electron Paramagnetic

Resonance Spectroscopy (EPR)

We would not expect to see an EPR in Pc compounds that do not have unpaired electrons. Compounds that are rather dilute

will not exhibit a measurable EPR either.

•EPR spectra can be obtained for systems having several unpaired electrons, but obtaining a background is rather difficult.

•Systems having an odd number of unpaired electrons are easier to detect whereas species with an even number of electrons can be difficult to detect.

Infrared Spectroscopy

• The infrared portion of the electromagnetic spectrum is divided into three different sections: near, mid and far infrared– (400-10cm-1) The far-infrared region has low energy

and it used for rotational spectroscopy– (4000-400cm-1) The mid-infrared region is used to

study vibrations and rotational-vibrations associated with structure

– (14000-4000cm-1) The near-infrared region has higher energy and excites overtone and harmonic vibrations

Background

• Infrared spectroscopy works by picking up different energy levels created by the specific frequencies of chemical bonds

• The different frequencies are determined by the shape of the molecule, the mass of the atoms and the bond energies

Group Vibrations of Porphyrins

GROUP Frequency (cm-1)

OH 3590-3610, 3367, 3330

NH 3310-3326, 975-990, 675-700

CH 2976-3077, 2849-2890, 1295, 986

CN 2208-2212

CO 1725-1740, 1640-1668, 905-930, 665

Instrumentation

• Perkin-Elmer Paragon 500 FT-IR Spectrometer – 4000-650cm-1

– 4 scans– 2.0 cm-1 resolution

• Sample prepared as KBr pellet– Mortar and pestle used to grind and combine the

product and KBr– 1:100 ratio used

Instrumentation

Metal-Free Phthalocyanine

Metal Phthalocyanine (Zn)

IR Analysis

• There are several peaks that are characteristic of compounds with benzene rings:– Vibrations of CC bonds of benzene rings are found at

1453cm-1 and 1474cm-1

– Other peaks can be found at 1608cm-1 and 1582cm-1

• The IR spectra of metal phthalocyanines and metal free phthalocyanines is particularly different in the region from 1600-200cm-1

IR of Metal Free Phthalocyanine

• Characteristic bands of metal free phthalocyanines:

– Band at 1010cm-1 is characteristic of the H2Pc ring vibrations

– Peak at 3341cm-1 and weak absorption band at 3280cm-1 is from the stretching vibrations of the N-H bonds

– There are several skeletal vibrations ranging from 1090-740cm-1 that are not present in metal phthalocyanines

IR Spectral Analysis

• In plane stretching vibration of N-H bonds enhances the peak at 1610 in the metal free phthalocyanine because of the existence of the extra NH2 group

• Metal Ligands absorb in the region at 200-550cm-1

• There are few other absorptions in this region• Metal phthalocyanines have strong absorption bands at

1470-1430cm-1

• Addition of the metal ligand causes different vibrational modes of the CH2 and CH3 groups

EPR: Background

• Method for the detection of unpaired electrons– Transition metals (Inorganic)– Free radicals (Organic)– Defects in materials

• Note: Paramagnetic means magnetism only occurs when an outside field is applied

EPR: Theory

• Spectroscopy = Measurement and interpretation of different energy states in an atom or molecule

• Planck’s Law:– ΔE=hv

– ΔE=hv=gμBB0

– “g-factor” = proportionality constant (≈2), varies on electronic configuration of the electron

– μB= Bohr magneton (unit of magnetic moment)

• Like NMR, an applied magnetic field B0 creates an energy difference between ms=-½ and ms=+½

• Unlike NMR, we are looking at spins from electrons (NMR investigates nuclear transitions)

EPR:Theory

Reference:http://www.chemistry.nmsu.edu/studntres/chem435/Lab7/eprsplit.gif

• Selection rule: only transitions between ±mI, I = nuclear spin

• +1->-1, -1->+1, 0->0

EPR Theory

• Zeeman effect:– The electron’s magnetic moment causes it to

align either parallel or anti-parallel to the applied magnetic field.

– Lowest energy: μ aligned with field (“parallel”, ms = -½)

– Highest energy: μ aligned against the field (“anti-parallel”, ms = +½)

– The energy of these two states diverge as the field is applied.

Reference: http://www.bruker-biospin.com/cwtheory.html

EPR:Theory

• Unlike conventional spectroscopy, continuous-wave EPR keeps the electromagnetic radiation (frequency) constant while varying the applied magnetic field.

• This is due to limitations in magnetic field applications

• Resonance occurs when the separation of the energy levels equals the energy of the microwave photons

Reference: P. Atkins, T. Overton, “Inorganic Chemistry” 4th edition, W.H. Freeman and Company, New York NY. 2006, p. 181.

EPR:Theory

• Frequency substantially affects the resonance field

• We used “X-Band”:≈9.75GHz. This is pretty standard for continuous-wave EPR.

• Others can be used to compliment information gathered with X-Band

Reference: http://www.bruker-biospin.com/cwtheory.html

EPR:Theory

• Hyperfine structure: The spin of an electron will couple to surrounding magnetic nuclei.

• This results in a local magnetic field at the electron: either supplementing or opposing the applied field

• This splits each Zeeman level into two more (2I+1)

• Selection rule: only Δms=+1, Δml=0 allowed

EPR:Theory

• Superhyperfine structure: shows the coupling of the metal to ligand nuclei– Shows the extent of delocalization and

covalent bond character

• Hyperfine and superhyperfine structure show what surrounds the metal: how many atoms, how close, etc

EPR: Applications

• Detects short-lived free radicals: used in biomedics for information on free radicals in toxicities, etc

• Spin-labeling paramagnetics is used to determine information about the environment around the label

• Provides information about metalloproteins• Radiation dosimetry: sterilization of medication /

food, identifying early human artifacts

Phthalocyanines & EPR

• The hyperfine structure of the EPR will depend on the metal in the phthalocyanine (copper should have four: I=3/2 for d9 complexes)

• Presence of superhyperfine structure will determine the delocalization / covalent character of the two nitrogen-metal dative bonds

EPR: MgPc

EPR: Analysis

• Since Mg is not a transition metal, no hyperfine structure is observed– The source of the unpaired electron must be

the ligand, not the metal

• The g-factor of 2.007 is slightly higher than ge of 2.0023, indicating a higher local magnetic field than the one supplied– Phthalocyanines are paramagnetic

EPR: Analysis

• If phthalocyanines are paramagnetic on their own, where does it come from?

• Studies on oxidation intermediates by Moser have proven that the unpaired electron is on some π-bond, and not on the central metal atom

• In a study done by Assour and Harrison, it was hypothesized that the unpaired electrons come from:– A chemical or physical impurity,– Presence of oxygen in the molecule, or..– A delocalized electron from a broken π-bond

Reference: Moser, Thomas, Phthalocyanine Compounds, Reinhold Publishing, New York 1963, pp49-52.

Reference: Assour, J. M., Harrison, S. E., Journal of Physical Chemistry, 1964 (68)872-4

EPR:Analysis

• Phthalocyanine is anisotropic: different magnetisms along different axes

• As a result, it is also an organic semi-conductor

• This is due to π-bond conjugation. Overlap allows electron flow between orbitals

• Delocalized π electrons are being detected by the EPR

UV/Vis

• Metalloporphyrins show many characteristic bands: two Q bands between 500 and 600nm, an intense B band between 380 and 420nm, and weak N, L, and M bands. N at ~325nm, M at ~215nm, and L in between N and M.

• The lower energy Q band comes from the electronic origin Q(0,0) of the lowest-energy excited singlet state. The higher energy Q band includes one mode of vibrational excitation Q(1,0). The B band is attributed to the origin of the second excited state B(0,0).

• The literature lists ranges for the molar extinction coefficients. For the the Q(1,0) band 1.2 to 2*104 L/mol cm, for B bands 2 to 4*105 L/mol cm.

M. Gouterman, in The Porphyrins, ed. D. Dolphin, Academic Press, New York, 1978, vol. III, p.12-17

UV/Vis

• The Beer’s Law plots shown here are for Ni(II), Co(II), Zn(II), and Cu(II).

• Only the spectra of Zn and Cu show N bands.• Many of the spectra showed signs of contaminants which is is most

likely the cause of the conflict between the theoretical and calculated molar extinction coefficients.

• The wavelength of the spectra increases for a series of metals: Pd(II), Co(II), Ni(II), Cu(II), Zn(II), V(IV)O, Mg(II).

• The Q and B bands are shifted towards the blue in all spectra, and according to the literature these bands to shift together.

599nm Beer’s Law Plot Ni PC

599nm of Ni PC

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0 0.00005 0.0001 0.00015 0.0002 0.00025

Concentration

Ab

sorb

ance

Slope = 2727 L/mol cm

666nm Beer’s Law Plot Ni PC

666nm Of Ni PC

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

0 0.00005 0.0001 0.00015 0.0002 0.00025

Concentration

Ab

sorb

ance

Slope = 3750 L/mol cm

597nm Beer’s Law Plot Co PC

Beer's Law Graph for 597nmCoPC

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0.45

0.5

0.00E+00 2.00E-06 4.00E-06 6.00E-06 8.00E-06 1.00E-05 1.20E-05 1.40E-05 1.60E-05 1.80E-05

Concentration

Abso

rban

ce

Slope = 27547 L/mol cm

657nm Beer’s Law Plot Co PC

Beer's Law Graph for 657nm for Co PC

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

0.00E+00 2.00E-06 4.00E-06 6.00E-06 8.00E-06 1.00E-05 1.20E-05 1.40E-05 1.60E-05 1.80E-05

Concentration

Abso

rban

ce

Slope = 93350 L/mol cm

344nm Beer’s Law Plot Zn PC

Beer's Law Plot at 344 nm Zn PC

00.05

0.10.15

0.20.25

0.30.35

0.40.45

0.00E+00 2.00E-06 4.00E-06 6.00E-06 8.00E-06 1.00E-05

Concentration (M)

Abs

orba

nce

(A)

Slope = 49796 L/mol cm

607nm Beer’s Law Plot Zn PC

Beer's Law Plot at 607 nm Zn PC

0

0.05

0.1

0.15

0.2

0.25

0.3

0.00E+00 2.00E-06 4.00E-06 6.00E-06 8.00E-06 1.00E-05

Concentration (M)

Abs

orba

nce

(A)

Slope = 30542 L/mol cm

637nm Beer’s Law Plot Zn PC

Beer's Law Plot at 673 nm of Zn PC

00.2

0.40.60.8

11.21.4

1.61.8

0.00E+00 2.00E-06 4.00E-06 6.00E-06 8.00E-06 1.00E-05

Concentration (M)

Abso

rban

ce (A

)

Slope = 194016 L/mol cm

325nm Beer’s Law Plot Cu PC

Beer's Law at 325nm Cu PC

00.20.40.60.8

11.21.41.61.8

0 0.00005 0.0001 0.00015 0.0002

Concentration

Abs

orba

nce

Slope = 8731L/mol cm

605nm Beer’s Law Plot Cu PC

Beer's Law at 605 nm Cu PC

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0 0.00002 0.00004 0.00006 0.00008 0.0001 0.00012 0.00014 0.00016 0.00018

Concentation

Abso

rban

ce

Slope = 3700 L/mol cm

671nm Beer’s Law Plot Cu PC

Beer's Law at 671nm Cu PC

0

0.5

1

1.5

2

2.5

0 0.00002 0.00004 0.00006 0.00008 0.0001 0.00012 0.00014 0.00016 0.00018

concentration

abso

ranc

e

Slope = 11469 L/mol cm

Conclusions

• Synthesis was successful– Yields for most phthalocyanines were over

50%– Loss of product due to….

• Not enough time refluxing• Not heating to high enough temperature• Poorly fitted filter paper to glass crucible

Conclusions

• Characterization of MPcs– IR Analysis

• Shows characteristic Pc peaks– Metal free Pc: Peak at 1010 cm-1 for central N-H bond– MPc: Didn’t have that peak, indicating metals bonded to N

• Comparison with known MPc spectra confirms product formation– Differences seen in slight shifts and peak intensity

– UV-Vis Analysis• MPc’s show characteristic absorption in the red region of the visible

spectrum due to conjugation of Pc ring structure– Except LiPc: Extra absorption peaks possibly caused by insoluble

product in pyridine.

– EPR Analysis• Shows paramagnetism of Phthalocyanine but is inconclusive

Future Applications

• The uses for phthalocyanines are expanding from their roles primarily as pigments and dyes.

• They are becoming important aspects of research in the following areas:– Organic Light Emitting Diodes (OLEDs)– HIV Treatment– Photodynamic Therapy

Organic Light Emitting Diodes

• Electrical current is applied to the cathode

• Transfer of electrons to the emissive layer, causes electrons from the conductive layer to move to the anode, leaving positively charged holes.

• Upon build up of charge, electrons and electron holes move towards each other (electrostatic attraction), and combine closer to the emissive layer

• Drop in energy of the electron results in light emission

Image Courtesy and Copyright © 1996-2005 Silicon Chip Publications Pty Ltd & Web Publications Pty Limited.

Organic Light Emitting Diodes

• Problem: Indium tin oxide (ITO) anode diffuses into the organic layer during operation.– Shortens lifetime

• Solution: Use of metal phthalcyanines (MPc) as hole injection layers on the ITO.– Absorbs light mainly from 600-700 nm, and

very weakly from 400-500 nm, making them ideal for blue-green displays

Organic Light Emitting Diodes

• Trials involving CoPc, CuPc, ZnPc, NiPc, SnPc, MnPc, and FePc as hole injection layers have found…– Bright green emission for all at λmax = 525 nm

– Increase in luminance: Co doubles luminance (Co>Ni>Zn>Cu>Mn>Fe>Sn>No MPC)

– Increase in emission efficiency– Significant decrease in turn-on voltage

• Except for SnPc and FePc

HIV Treatment

• Human immunodeficiency virus (HIV) – An estimated 38.6 million people in the world had HIV

at the end of 2005.

• The development of drugs could prevent viral infection from sexual transmission– Inhibit virus transfer into cells through membrane

fusion and endocytosis– Must exhibit no cytotoxic effects

HIV Treatment

• Investigations of sulfonated NiPc, CuPc, and other sulfonated tetra-pyrrole derivatives in vitro show…– Inactivated >90% of HIV-1 B subtypes– Blocked >90% of HIV-1 C subtypes– Blocked >85% of HIV-1 A subtypes– Illustrated little or no cytotoxic effects– Blocks infection of HIV subtypes at

coreceptor CCR5.• In other testing, CuPcS blocked ~95%

of infection by cell-associated virus transfer, while NiPcS blocked ~80%.

HIV Treatment

• Tests for inactivation of HIV at varying pHs were also done.– Need inactivation from pH

4.0 to 7.0 – Pc with no metal had a

dramatic change in inactivation at lower pHs

• Pretreated cells with the PcS compounds were also tested for inhibition of HIV infection– Showed similar results as

with post-treated cells

Compounds were incubated with HIV-1 in a sodium citrate-citric acid buffer of varying pHs for 1 hr. Cells were inoculated and then checked for infected cells 3 days later.

Photodynamic Therapy

• Cancer treatment that involves a photosensitizer (drug) and visible light to destroy targeted tissue.– Light promotes the drug to

electronically excited state. This energy is transferred to O2, which creates singlet oxygen.

– Singlet oxygen is highly oxidizing and cytotoxic, which allows it to destroy cancer cells.

• First approved PDT drug was Photofrin, a hematoporphyrin derivative, in 1995.

• Several other drugs have been approved since then

Photodynamic Therapy

• Still a need for new drugs that can…– Absorb light in far red region– Enhance singlet oxygen

production

• Phthalocyanines have great potential as PDT drugs.– Except they’re hydrophobic

and to enter cells they need to be hydrophillic.

– Water soluble derivates of Pc have been made, but hydrophobic forms have better PDT performance

• Development of Au nanoparticle delivery system– ZnPc derivatives with thiol

moiety self-assemble to Au surface

– Combine ZnPc derivatives with gold salt, a phase transfer reagent (TOAB), and sodium borohydride as a reductant.

– Increases solubility in polar solvents like ethanol and water

Photodynamic Therapy

• Nanoparticles were incubated with HeLa cells to see if they were incorporated into the cells via endocytosis.– Fluorescence Microscopy shows internalization of

photosensitizers

• Showed increase of singlet oxygen quantum yield from 0.45 to 0.65

• ZnPc Au nanoparticle system shows decrease to 77% cell mortality after incubation for 4 hours, and a 43% cell mortality after subsequent irradiation at 690 nm for 20 minutes.

Photodynamic Therapy

• Fluorinated ZnPc compounds exhibit increased singlet oxygen production, when compared to metal free compounds.– Also show cell mortality upon

irradiation against EMT-6 tumor cells

• Hydroxy-pyridine ZnPc species exhibited similar cytotoxicity towards human colon adenocarcinoma cells when compared to Photofrin.

Acknowledgements

• Dr. Kirschenbaum

• Carolyn Higgins

• Dr. Euler

References

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