Photodynamic Therapy: An overview

The use of light in medical treatment is nothing new. In the ancient world, roots of the plant Dorstenia were applied topically on to irritated skin which would clear following a few hours of sunshine. The active ingredient, psoralen, is now the basis of PUVA (psoralen + UVA) therapy used to treat the effects of psoriasis and other skin ailments. Psoralen acts by intercalating between base pairs of DNA and upon UV irradiation, the two double bonds form [2+2] cyclo-adducts with thymine, kinking and destroying the DNA of the replicating cells, which was causing the skin irritations in the first place.

In the early twentieth century, following significant progess in synthetic chemistry of coloured dyes throughout the nineteenth century, two German scientists completed work on the toxic effect of eoisin, a methylene based dye. The effect was only noted with the presence of light, and at a later date the presence of oxygen. Thus the modern day science of photodynamic therapy (PDT) was discovered, consisting of three components: photosensitising dye, light, and oxygen. Despite positive results from trials, the work went relatively unnoticed, and it wasn’t until the 1970s that it really picked up again.

Fundamentals

The basic principles of PDT are relatively easy to consider. A light absorbing dye is applied or injected into the patient and after a time appropriate for maximum uptake into tumour, the affected area is irradiated with light. The dye absorbs the incident light and an electronically excited state is formed. This subsequently generates a reactive oxygen species (ROS) which destroys the tumour. The concept is beautifully simple, and as the dye is non-toxic in the absence of light, does not carry the negative effect of traditional chemotherapies which are much less discriminate in their action. In PDT, only irradiated areas of body tissue will generate activity leading to cell destruction. As mentioned, there are three components to PDT: light, photosensitiser and oxygen. the latter two are considered in turn, below.

Oxygen

The net result of dye irradiation is the generation of reactive oxygen species, and it is generally considered that singlet oxygen 1O2 is the ROS responsible for cell destruction in PDT. 1O2 is formed when oxygen, which in the ground state exists in as a triplet (3O2 ) absorbs energy. According to the MO diagram of the ground state 3O2 shown, the singlet is formed with the pairing of electrons in the LUMO. This is energetically unstable relative to the ground state, as there is a vacant orbital of the same energy available to the paired electron. Hence, 1O2 is energetically higher (thus more reactive) and will return to its triplet ground state. The lifetime of the singlet state in a cell is of the order of 100s of ns, and it has been estimated that it can diffuse less than 50 nm in this time. Therefore, in cells of the order of microns, the action is limited to cellular dimensions.

1O2 is formed by energy transfer from the photoexcited dye. But an alternative is possible. If the photoexcited dye transfers an electron to molecular oxygen, a superoxide anion is formed. Therefore, a crucial aspect of drug development in PDT is the nature of the ROS formed. Electron transfer forming superoxide anion is called a Type I reaction. Energy transfer forming 1O2 is called a Type II reaction. We can distinguish between these by understanding the chemistry behind them. Importantly for us here. Type II is detected because as singlet oxygen returns to its triplet ground state, it emits a small amount of infrared phosphorescence, which can be detected (see figure – the emission maximum is approximately 1270 nm). Type I on the other hand, can be detected by monitoring the redox chemistry of Fe3+ and subsequent formation of hydroxyl radicals (the photo-Fenton mechanism).

Singlet oxygen emission

Photosensitiser

The photosensitiser has several functions. It must locate in the tumour. This involves considering both hydrophilic and lipophilic components in the molecular design that are not covered here. It should also absorb in the far visible region (600 – 800 and preferably 700 – 800 nm). Haemoglobin is a significant component of body tissue, and absorbs strongly in the mid visible region (580 nm). This is obvious when we shine a light through our hand – only red light passes through. Therefore the ideal will be one which absorbs light where the body does not, allowing them to be used deep within body tissue (e.g. liver, pancreas).

As it stands, clinically approved PDT drugs are not yet optimised for longer wavelength light absorption, and hence PDT treatment is currently limited to areas that are easy to expose to a light source: skin, lung, oesophagus, etc. This issue of “penetration depth” was the subject of a recent court case, whereby a doctor justifiably claimed that PDT treatment would not be suitable for treatments such as liver cancer, as the liver was just too big for light to pass through. (The doctor was subsequently acquitted of all charges). The bar chart (Ref 1) shows how photosensitiser absorption capacity affects penetration depth, and this is the focus of current research (below). Penetration doubles once light at longer wavelength than the absorption of haemoglobin is achieved (630 nm) and doubles again at 700 nm. An ideal photosensitiser will therefore absorb between 700 – 800 nm.

Other factors for an ideal photosensitiser include: low toxicity in the absence of light and little post-treatment side affects. One of the most significant side effects is post-treatment light sensitivity, whereby patients have to avoid light for fear that healthy body tissue which have residual amount of photosensitiser present will generate unwanted activity.

Jablonski Diagram for generation of singlet oxygen (ref 1)

From a photochemical point of view, one of the most important dye characteristics is that it will form a high concentration of triplet excited state. Since the mechanism of action is generation of singlet oxygen, a singlet state may not be long-lived enough to allow time for reaction with oxygen (singlet-singlet deactivation via fluorscence or non-radiative means is an allowed process, and therefore very fast). If the triplet forms via intersystem crossing, its deactivation is forbidden, and hence slower, allowing the energy transfer to oxygen to be more competitive. This again provides potential for future research (see below).

Photofrin

Photofrin (R)

The first clinically approved PDT drug was photofrin (R). Photofrin is a porphyrin -based compound and you may wish to examine its structure to identify hydrophilic and lipophilic components alluded to above. It absorbs at 630 nm, which is within the PDT window and has a respectable quantum yield of inter-system crossing of about 25%. However, its absorption is not significant, with a low extinction coefficient. Its worth noting here also that PDT is not limited to cancer based therapy, it has also been used as alternative to antibiotics and for gum disease (There is a good overview article in Chemistry World, ref 2, and some nice pictures for dental treatment at the Periowave site, ref 3)

Current Developments

Absorption spectra of chlorins and bacteriochlorins (Ref 1)

Photofrin’s limitation is primarily its light absorption. To get to a point where PDT can become more versatile, the photosensitiser needs first to absorb in the 700 – 800 nm window (and then subsequently satisfy all other demands re singlet oxygen generation, accumulation in tumours….). Reduction of one (chlorins) and two (bacteriochlorins) of the four pyrroles in porphyrin based compounds have been found to shift the wavelength of absorption to longer wavelengths. In the example shown, the absorption shifts to about 700 nm for chlorin-based molecules and to about 800 nm for bacteriochlorin based molecules. The compound shown has a high extinction coefficient of absorption and good oxygen generation capabilities. More information on these compounds is available in Ref 1.

Intersystem crossing can be enhanced by the heavy atom effect, and this is the subject of another class of boron-based compounds. It was noted for certain sites of substitution of iodine, the singlet oxygen generation capacity increased, attributed to an increased intersystem crossing yield caused by the iodine heavy atoms. More information on these compounds is available in reference 4.

Utilising heavy atom effect to enhance ISC (Ref 4)

Summary

PDT provides huge potential in treatment of cancerous tumours and a range of other antibiotic treatments. It has been called a very selective surgeon’s knife thanks to its ability to isolate the affected area for treatment with little collateral damage. At the core of future developments of PDT is an understanding of the photochemistry at its heart, and now a century after the first PDT action was discovered, it looks like it has a positive future.

References

1. (Primary reference for this article) Chem Soc Rev, 2011, 40, 340: Sections A, B, C.1, C.4, D, F.2, F.3

2. Chemistry World, 2012, April, 52, see also Education in Chemistry, 2004, May, 71.

3. Periowave blog (accessed December 2012)

3. Chem Soc Rev, 2013, 42, 77: pages 77 – 81.

Avatar and Photochemistry: Chemiluminescence

Photochemistry for an Oscar? In the movie Avatar, it plays a central role, although I must admit I didn’t see it listed in the credits… The movie is set on a planet called Pandora, and at night time, the forests of Pandora light up to give some really beautiful cinema, all in 3D! This article explains the glow in the trees, insects, inhabitants and just about everything else on Pandora at night time. Back on Earth, we’re familiar with this glow too!

When some chemicals react, they can give off or require huge amounts of energy in doing so, as existing bonds are ripped apart and new ones form. This energy is in the form of heat – reactions can give off heat (exothermic) or require heat to proceed (endothermic). More unusually, the can give off large amounts of energy in the form of light. This light is called chemiluminescence. In photochemistry, we are usually concerned with providing molecules with light to activate a reaction. With chemiluminescence, it’s the other way around – a chemical reaction results in the emission of light. The classic demonstration of chemiluminescence is with a compound called, appropriately enough, luminol. Here’s a short Youtube video on it (with a rather excited chemist).

So what is happening?

Let’s look closer at the luminol reaction. When hydrogen peroxide (e.g. from household bleach) is added to luminol, in the presence of base and a catalyst (such as iron(III) which gets involved in the oxidation), 3-aminophthalate is formed. But the energy involved in the oxidation of luminol by the peroxide results in the phthalate having an electronically excited state. The releases this excess energy by emission of light, giving the blue colour observed.

Luminol Reaction

Luminol reacts with hydrogen peroxide to produce an electronically excited 3-aminophthalate, which emits in the blue (450 nm)

Applications of chemiluminescence

Natural World

One of the most common observations of chemiluminescence, as any inhabitant of Pandora will know, is bio-chemiluminescence, or bioluminescence, which is where natural world has exploited the use of chemiluminescence. The most commonly known example of this is the firefly (Photinus), which uses a reaction similar to that of luminol, and an enzyme, luciferase, in place of the peroxide, along with magnesium ions to produce a glow (the colour depends on the type of fly).

Oxidation of Luciferin

Oxidation of Luciferin by luciferase in the presence of magnesium ions gives emission (e.g. in the yellow region)

As well as Pandora, back on Earth, Irish swimmers came across some beautiful examples of bioluminescence off the coast at Killiney when “spectacular green neon flashes” in the sea were observed by swimmers as they swam through water. This was determined to be the plankton Noctiluca scintillans, which is reported to be known as “Sea Ghost” or “Fire of Sea”.

Image of Noctiluca

Image of Noctiluca Scintillans (taken from Maria Antonia Sampayo, http://planktonnet.awi.de, Creative Commons Attribution 3.0 License)

Analytical Applications

Given that emission spectroscopy is such a versatile analytical tool, it is perhaps no surprise that chemiluminescence has several potential applications in the area of chemical analysis. The intensity of luminescence is proportional the the concentration of reactant. In principle, analysis does not need the same level of instrumentation as emission spectroscopy – which needs a light source to excite the sample and emission my be detectable by eye. Therefore it can be used in crude analytical tests. Luminol is used to test for blood at crimescenes – a luminol spray on any suspected blood traces results in the iron in the blood catalysing luminol chemiluminescence, and glows for up to a minute after being sprayed.

But there is more scope for its use. Two problems to its adoption as an analytical technique are that the quantum yield of emission can be low, which means that at low concentrations, the detection may be difficult. In addition to potentially poor sensitivity, long lived emission (such as those observed in glow sticks and luminol), which makes for great demonstrations, means that response time is unnecessarily long. Some work on both of these areas is advancing. Coupling the chemiluminescence interactions with metal nanoparticles harnesses the surface plasmon resonance effect, where the emission from the chemiluminescence couples or resonates with the electron density of the nanoparticles, which enhance the signal, with reports of a 4 – 10 fold increase. The efficient transfer of energy from the excited state of the reagent to the nanorparticles also significantly reduces their lifetime, hence the lingering glow. Readers interested in this work are referred to Aslan and Geddes, given below.

This being said, chemiluminescence is already in use to study a wide range of medicinal and environmental-related compounds in a technique that couples chemiluminescence with liquid chromatography (HPLC-CL). The reagents used in this technique include the now familiar luminol, which is used to investigate lipid hydroperoxides, neurotransmitters such as dopamine (which enhance the chemiluminescence), and environmentally relevant species such as organophosphorus reagents (e.g. diclorvos). The always familiar Ru(bpy)32+, which as well as everything else can exhibit chemiluminescence, undergoing reduction by analytes in high energy electron transfer reactions to produce the excited state. This system has been used to study nitrosamines, N-methylcarbamates pesticides in pear and apple samples and domoic acid which can be a factor responsible for shellfish poisoning. There are several set-ups possible for interfacing the chemiluminescence set-up with the HPLC; most simply by having an injection point after separation for the chemiluminescent reagent prior to the emission detector. A very detailed review of the use of chemiluminescence in medicinal, food and environmental analytes is that by Gámiz-Gracia et al.

Finally, it is worth noting that a lot of gas-phase reactions result in chemiluminescence. This is the basis of gas analysers, for example the nitrogen monoxide analyser. Nitrogen monoxide reacts with ozone to produce an excited state nitrogen dioxide which emits in the far visible/infrared region. The extent of luminescence can be related tot he initial concentration of NO.

Your very own magical world

If you want to set up your own version of Pandora, which cost James Cameron $250M, you can do it for a few euros, by buying some glow sticks and dotting them around. Their glow lasts for a few hours, so all you need is a little imagination during this time…

References

Lights in Sea are Natural“, Irish Times, www.irishtimes.com, 18 October 2009

K. Aslan and C. D. Geddes, “Metal-enhanced chemiluminescence: advanced chemiluminescence concepts for 21st century“, Chem. Soc. Rev., 2009, 2556 – 2564.

Laura Gámiz-Gracia, Ana M. García-Campana, José F. Huertas-Pérez, Francisco J. Lara, “Chemiluminescence detection in liquid chromatography: Applications to clinical, pharmaceutical, environmental and food analysis—A review“, Anal. Chim. Acta, 2009, 640, 7 – 28.




Beautiful Photochemistry

I came across this nice blog recently and thought it was worth signposting here. It is called “Beautiful Photochemistry” and its author writes summaries  of recent articles from some leading chemistry journals which have a photochemical basis. There are some great synopses on a range of topics within photochemistry, including one I was very happy to see on enone-alkene cycloadditions.

Beautiful Photochemistry Blog: http://beautifulphotochemistry.wordpress.com/

 

Quenching Mechanisms

Excited states can be deactivated in several ways – they can emit, giving off light energy, deactivate – resulting in a “vibrationally hot” ground state (i.e. energy loss as heat) or be quenched by another molecule. In this section, we will consider the process of quenching, and outline some ideas that use the process of quenching in applications. In addition, we will examine how the process of quenching can be studied to give us information on the nature of the excited state-quencher interaction. It is assumed the reader is familiar with the information presented in the Light Absorption and Fate of Excited State post.

Overview

Quenching of the excited state is a significant process because it is usually a very efficient process. The excited state of many organic compounds, for example, are efficiently quenched by the presence of oxygen, at rate constants several orders of magnitude faster than emission processes from the triplet state. (Emission from the triplet is spin forbidden, and hence has rate constants in the range 10 to 103 dm3 mol-1 s-1, whereas oxygen quenching may take place at rate constants of the order 109 dm3 mol-1 s-1. Therefore, to study the emission from triplets, we need to deaerate the sample (and have it at low temperature – see the experimental section). Quenching processes can occur by two processes – electron transfer or energy transfer. In both cases, the excited state energy of the luminophore (the luminescent species) is deactivated due to the presence of the quencher. There are two scenarios by which quenching is generally modelled, and these are discussed below.

Dynamic Quenching of an Excited State

If a solution with emitting species is studied, and for every 100 photons absorbed by the solution, 30 are re-emitted, the quantum yield of emission is said to be 0.3. What happens to the other 70? They are translated into radiationless transitions, such as deactivation. As mentioned in the Ruthenium polypyridyl photochemistry post, we can quantify the quantum yield of emission (or any process) as being the rate constant of that process (in this case emission) divided by the sum of all rate constants deactivating the excited state. If we divide the emission quantum yield in the absence of quencher by that in the presence of quencher, we can generate an expression known as the Stern-Volmer equation, as shown below.

SV_quenching

Derivation of the Stern-Volmer Equation based on considering rate constants of deactivation in the absence and presence of quencher

The Stern-Volmer equation models what is called dynamic quenching, quenching which occurs by the quencher diffusing through solution and interacting with luminophore, resulting in a deactivation of the excited state. The emission intensity is reduced, because as well as other deactivation pathways before the presence of quencher, the presence of quencher now adds another deactivation pathway in competition with luminescence. This quenching process is controlled by how fast the quencher can diffuse through solution and “collide” with luminophore, and as diffusion is usually a very fast process in solutions, it can be very efficient.

The Stern-Volmer equation is the equation of a straight line, and hence it allows for  very easy experimental determination of the quenching rate constant, kq. If the emission intensity (or lifetime) in the absence of quencher and then in the presence of incremental amounts of quencher is measured, and the resulting ratio of emission intensities (I(0)/I) is plotted as a function of quencher concentration, the resulting graph (called a Stern-Volmer plot) will have an intercept of 1 and a slope called the Stern-Volmer constant, KSV. KSV is the product of the natural radiative lifetime (the lifetime in the absence of quencher, τ0, and the quenching rate constant, kq. Knowing the slope and the natural radiative lifetime allows easy calculation of the quenching rate constant. An outline of a common experiment – quenching of a ruthenium polypyridyl complex emission with Fe3+ is shown below.

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The fact that quenching can be so efficient means that it can be a useful probe in studying systems with emission properties. For example, ruthenium polypyridyl complexes have been used successfully as oxygen sensors, whereby the complex has been incorporated into a silica matrix and the resulting stub located inside packaging. In the absence of oxygen, emission is observed when the stub is irradiated with light. However, if oxygen leaches into packaging, the emission observed will be substantially reduced, as it will be quenched by the oxygen. By calibrating the reduction in intensity using a Stern-Volmer plot, it is possible to estimate the concentration (partial pressure) of oxygen in the system. The concept has applicability in food packaging and for containers holding oxygen sensitive artefacts (e.g. paintings).

Static Quenching

Dynamic quenching results from collisions between excited state and quencher. However, if the quencher is somehow associated with the luminophore in solution prior to light absorption, the association may mean that the luminophore will not emit, due to induced changes in its properties because of presence of quencher. Therefore the reduction in emission intensity will be affected by the extent to which the quencher associates to the luminophore and the number of quenchers present. The reduction in emission intensity can be quantified as follows. If the luminophore, M, associates with quencher, Q according to an equilibrium constant of association, Ks, then this association constant can be quantified as the ratio of associated luminophore-quenchers luminophore-quenchers moieties ([M-Q]) to the product of unassociated luminophore and quencher; [M][Q]. Since the total concentation of luminophore, [M]0 is equal to the sum of associated and unassociated luminophore, substitution of this into the equilibrium expression, followed by rearrangement results in another equation of a straight line, very similar in form to the Stern-Volmer equation. However, while plotting I0/I (as emission intensity can be said to be proportional to concentration) against [Q] will result in a straight line for static quenching, analogous to dynamic quenching, interpretation of the slope is different. In this case, the slope quantifies the association constant between quencher and luminophore – and therefore is useful in providing information on how these two species interact in the ground state.

static-quenching

Derivation of an expression for static quenching

Dynamic or Static?

The question that immediately arises now is that if plots of emission intensity against quencher concentration both produce straight line graphs, how do we know which type of quenching is occurring? The answer lies in thinking again about the nature of each type of quenching. For dynamic quenching, all luminophores are affected by the quenching process as it is probable that they will all collide with a quencher during their excited state lifetime, so both emission intensity and lifetime reduced on increasing quencher concentration. For static quenching by association, only luminophore-quencher associations result in reduction in emission, unassociated luminophores are free to luminesce as if there was no quencher present. Increasing quencher concentration affects emission intensity, because there are more associations, but not emission lifetime, as the unassociated luminophores can emit in the absence of quencher. (Note that these two scenarios are the extremes, and there are cases where a mixture of both static and dynamic quenching may occur simultaneously.)

dynamic_versus_static_quenching

Schematic of dynamic versus static (association) quenching

Therefore the diagnostic test for assigning whether a quenching mechanism is dynamic or static is to compare how the emission intensity and emission lifetime changes as a function of increasing concentration. In the case of dynamic quenching, plots of relative emission intensities and emission lifetimes will be th same, changing on increasing quencher concentration. For static quenching, only a plot of relative emission intensity will change, the emission lifetime plot will have  slope close to zero.

diagnostic_plots

Model diagnostic plots to distinguish between dynamic and static quenching

Another model of static quenching is where the quencher is in a fixed position close to the luminophore (e.g. in a frozen matrix or a zeolite). This is modelled by the Perrin model of quenching, which will be discussed in the experimental techniques section when discussing phosphorescence.

References

MK Seery, N Fay, T McCormac, E Dempsey, RJ Forster, TE Keyes, Photophysics of Ruthenium Polypyridyl Complexes formed with lacunary polyoxotungstates with iron addenda, Phys. Chem. Chem. Phys., (2005), 19(7), 3426 – 3433. An example showing unusual static quenching between a quencher (large polyoxometallate clusters) and a luminophore (a ruthenium complex).

B Valeur, Molecular Fluorescence: Principles and Applications, Wiley: Weinheim, 2002. Discusses the principles of dynamic and static quenching well.

Our Energy Future: Lecture by Prof Tom Meyer

Prof Tom Meyer, Energy Frontier Research Centre, University of North Carolina, was in Dublin to participate in a Dublin Region Higher Education Alliance Master Class on Solar Energy. Afterwards, he gave a public lecture on “Our Energy Future: Science, Technology and Policy Challenges for the 21st Century – A US Perspective“. The lecture was held at TCD, and was sponsored by the Royal Society of Chemistry Republic of Ireland Local Section. It considered the various current and future world energy demands, and the role renewable energies have to play in providing this energy. My summary is given below.

Prof Thomas J Meyer has been researching the photochemistry of ruthenium complexes since the late 1960’s. Much of what we know about electron transfer in ruthenium polypyridyl complexes today is due to work conducted by Meyer and others in this period. Meyer worked with Henry Taube, who won the Nobel Prize in 1983 “for his work on the mechanisms of electron transfer reactions, especially in metal complexes”, publishing a paper with him in Inorganic Chemistry (1968) on excited state oxidation potentials of ruthenium-amine complexes. This work was an important pre-cursor to a 1973 paper published by Taube, Meyer and co-workers on the reduction of oxygen by these complexes. In the mid-1970’s, at a time when the oil crisis of the time was reaching a peak, Meyer published a series of important papers in Journal of American Chemical Society on the nature and kinetics of quenching of ruthenium amine complexes (including ruthenium – tris-bipyridyl) which gave great kinetic and mechanistic insight into the electron transfer between the metal complexes and an array of quenchers. Meyer reiterated in an article written in 1975 the importance of understanding electron transfer in the study of energy conversion, especially so with metal complexes as these absorb strongly at wavelengths of solar interest.

Prof Meyer, speaking at TCD on "Our Energy Future"

A surge of interest in these systems was observed the oil crisis, which faded somewhat in the 80’s and it wasn’t until Gratzel’s work on dye-sensitised solar cells, reported in 1990, that generated efficiencies that would allow for devices to become realistic contributors to energy supply. Since that itme, work has been concentrating on enhancing light absorption capacity, currently champoined by a ruthrnium dy “N3” (see DSSC post), as well as considering and optimising electron transfer processes in the solar cell devices.

Meyer’s lecture in TCD considered the current and future status of energy demands. It was a message he has delivered to the american political system, across administrations, during his tenure at the Los Alamos National Laboratory. Meyer reported that in the US, energy costs make up 7 – 10% of the cost of living, and 7% of overall world trade. A large demand in energy increase has been observed since 1900’s and this surge is expected to continue until at least 2100. While current stable economies’ energy usage will level off, emerging and transitional ecomomies (China, India, etc) will place major demands on the world’s energy supply. In the six years since 1999, China and India increased their energy usage by 80% and 25%, respectively (Cicerone). (A presentation by Cicerone, Preseident of the National Academy of Sciences is reference below and places thes enegy demands in context). In summation, >100 TW of additional ‘clean’ energy will be required by 2100.

The US currently uses 26% of the world’s oil supply, greater than the next five net using countries combined. 26% of the world’s oil is in the middle-east. Globally, the cost of oil is increasingly expensive to extract, as reserves become more and more difficult to source. Therefore additional energies from alternate sources is required to factor the loss in and increasing expensive of oil production; as well as the surge in energy demand from emerging economies. In addition, this energy supply must be in the context of envrironmental considerations, primarily global warming.

Meyer outlined several strategies to large scale energy production. Principal among these were nuclear, solar, and clean hydrocarbons. These and others are considered below.

Coal currently supplies 27% of the world’s energy demands, including half of US energy needs. It is also responsible for 35% of US carbon dioxide emissions. In principle, it could provide increased energy requirements until 2050, if 1% of GDP was used in dealing with carbon dioxide sequestration. The story of coal usage inclues the story of FutureGen – an initiative announced by the Bush administration in 2003. This was aimed at using coal as a clean fuel, with achieved targets of 275 MW of energy production with 90% carbon dioxide sequestration. However, the project was cancelled by the Bush administration in Jan 2008, due to massive cost overruns ($900M). The Obama adminsitration has restarted this work (June 2009), recognising that clean coal will be a crucial element to supplying energy demands in the forseeable future. Oil shale and tar sands are estimated to contain 2 trillion barrels of oil. However, it expensive (requireing a lot ofwater) and enviornmentally damaging to extract oil from these reserves.

Hyrdogen fuel is obtained from a variety of sources – primarily methane, but also from coal extraction and water electrolysis. In the latter case, electrolysis of water to produce hydrogen (and oxygen) is utililised by photochemical processes. Meyer identified the Idaho National Laboratory hydrogen programme as one which was making good progress in the production of hydrogen as a mass fuel. The advantages of hydrogen were good efficiency, and water and heat as emission products. However, the current costs (for transportation) are ca. $3500/kW, with a target of $35/kW. Another significant problem with the use of hydrogen was storage and transportation, which were expensive because of the nature of the fuel.

Nuclear energy provids ~20% of US energy, and increased usage would result in a significant decrease in greenhouse gases. There are 44 nuclear reactors currently being built internationally, and therefore these will be significnat contributors in to the future. The issues, well know, of nuclear power are what to do with waster, control (political issue), reprocessing and general safety issues.

Renewable energies provide an alternative approach to the solution. It is estimated that wind could provide 20% of US energy requirements. However, solar energy is a real viable option, given that 26,000TW per year of sunclight isiincident on the Earth’s surface (net amount after absorption etc). the technology is on the cusp of mass implementation, with some lingering problems regarding efficiencies. (In the US, there are also problems regardingthe arrangement of the national grid (see Grid 2030 project). Current estimates are that solar generation of 3 TW, assuming 10% efficiency solar cells, would cost approximately $60 Trillion (covering an area of 57k sq – miles). Current and future work will be focussed on reducing this cost.

Meyer reiterated the point in his talk, and again in questions, that there must be a political will to drive this work forward. Solar energy could have emerged as a major player much earlier, if work started after the oil crisis had continued apace. 6% of US energy is currently sourced from renewable sources; with 85% from coal, oil and gas. The hope is that by 2059, these numbers can be reversed!

References

C. R. Bock, T. J. Meyer, D. G. Whitten, Photochemistry of transition metal complexes. Mechanism and efficiency of energy conversion by electron-transfer quenching, J. Amer. Chem. Soc., 1975, 97, 2909 – 2911.

R. J. Cicerone, National Academy of Sciences, Address to the 145th Annual Meeting, available at: http://www.nationalacademies.org/includes/NASmembers2008.PDF [Oct 2009]

Las Alamos National Lab: National Security Science: http://www.lanl.gov/ [Oct 2009]

T. J. Meyer and H. Taube, Electron transfer reactions of ruthenium ammines, Inorg. Chem., 1968, 7, 2369 – 2371.

J. R. Pladziew, T. J. Meyer, J. A. Broomhea, and H. Taube, Reduction of oxygen by hexamammineruthenium(II) and by tris (ethylenediamine) ruthenium (II), Inorg. Chem., 1973, 12, 639 – 643.

H. Taube, Nobel Prize Lecture Nobel Prize 1983, http://nobelprize.org/nobel_prizes/chemistry/laureates/1983/taube-lecture.html [Oct 09]

R. C. Young, T. J. Meyer and D. G. Whitten, Kinetic relaxation measurement of rapid electron-transfer reactions by flash photlysis – conversion of light energy into chemical energy using Ru(bpy)3(3+)-Ru(bpy)3(2+*) couple, J. Amer. Chem. Soc., 1975, 97, 4781 – 4782.

Metal Oxide Photocatalysis

Metal oxide photocatalysis is based on the use of metal oxides (for example titanium dioxide) as light-activated catalysts in the destruction of organic and inorganic materials and in organic chemistry synthesis. In this article, we will be looking at the use of thee types of materials in the degradation of organic matter, which has applicability in environmental remediation (aqueous and air-borne) and self-cleaning surfaces. The technique is already widely used in commercial applications, but is still hampered by one significant limitation. These materials generally absorb primarily ultra-violet light, and research in recent years has been concentrating on developing visible-light active materials, with an emphasis on nano-particulate materials to maximize surface area. This article discusses the background to metal oxide photocatalysis, using titanium dioxide as the exemplar material, and looks at strategies being researched to enhance the photocatalytic efficiency.

Introduction

Titanium dioxide is a white powder, with titanium in oxidation state IV. Its d-electron configuration is therefore d0, and the white colour is explained by the lack of d-d or metal centred transitions. It exists in several polymorphs – two of interest here: anatase and rutile. As it is a semiconductor, its HOMO is termed a valence band and LUMO is termed a conduction band. Light absorption effectively results in a ligand to metal charge transfer, electrons from oxygen are transferred to the vacant titanium d-orbitals. For anatase (3.2 eV) and rutile (3.0 eV), this transition is in the UVA region, resulting in a sharp absorption band at 390 – 400 nm.

Looking more closely at the electronic processes, promotion of an electron to the conduction band, on irradiation by UV light, results in a ‘hole’ in the valence band – essentially a detriment of the electron density that was localised on that orbital, and usually assigned a positive charge to symbolize the loss of negative electron (of course negative and positive are just arbitrary notations). The hole is powerfully oxidizing – the orbital very much wants to retrieve electron density just lost after light irradiation. It can retrieve this simply by the electron in the conduction band recombining with the valence band – recombination is a sum of radiative (i.e. emission may be observed) and non-radiative processes. Based on the energy gap law, the fact that rutile energy levels are closer mean that the non-radiative process is more efficient, and hence recombination is more efficient. This is an important observation which we will return to shortly.

Alternative pathways to recombination are possible, and as you can guess, these result in the use of these materials as photocatalysts. The hole has the potential to oxidise water that may be on the surface of the material resulting in the formation of hydoxyl radicals. Hydroxyl radicals are themselves very powerful oxidisers, and can easily oxidise any organic species that happens to be nearby, ultimately to carbon dioxide and water. Meanwhile, upstairs in the conduction band, the electron has no hole to recombine with, since it has oxidised surface bound water. It quickly looks for an alternative to reduce, and rapidly reduces oxygen to form the superoxide anion. This can subsequently react with water to form, again, the hydroxyl radical. The processes are summarized below.

Top: Light of energy exceeding band gap results in charge separation, with electron reducing a donor (usually oxygen) and hole oxidising a donor (usually water); bottom: summary of processes occuring

Top: Light of energy exceeding band gap results in charge separation, with electron reducing a donor (usually oxygen) and hole oxidising a donor (usually water); bottom: summary of processes occuring. Image based on Bahnemann (2004).

At the level of the material’s surface, the requirements for efficient photocatalysis can be deduced from the electronic reactions – there should be surface bound water to allow for efficient oxidation; and the water should be aerated to provide oxygen to the solution. Additionally, the degradation of the pollutant by the catalyst requires for the pollutant to be adsorbed or very close to the surface of the material, and hence the greater the surface area of the material, the more pollutant can adsorb. Nanoparticulate materials are therefore preferred as they vastly increase the surface area (see DSSC post).

Pilkington self-cleaning glass is an example of use of this technology in a commercial application. A thin film of nanoparticulate titanium dioxide is coated onto panes of glass (it is so thin that it is transparent). The glass is in the normal course of events, acquiring dirt. The titanium dioxide on the glass, once exposed to sunlight, produces hydroxyl radicals which degrade any surface adsorbed dirt. Once washed down with rain, this decomposed dirt is removed and the glass is ready for another cycle. The same process is observed for any organic species – they react with the hydroxyl radical to ultimately form carbon dioxide and water.

Given that the materials work readily, it is a good time to detail the limitations. the primary limitation is that the materials absorb only UV light, so the activation by sunlight is completed by the 5% of sunlight that is in the UV region. A large amount of research has looked into ways to enhance the visible light activity of the materials. Another limitation is the fact that recombination is an efficient, competitive process, and given that this is a less efficient process with anatase, it is generally accepted that anatase is a preferred photocatalyst to rutile. Below, we will discuss approaches taken to both increase the visible light absorption capability and increase the efficiency of subsequent reactivity over the recombination process.

Moving to Visible Light Absorption Capability

Given the requirement for UV light activation of TiO2, researchers became interested in tuning the materials so that they would become activated by visible light (e.g. room light) for applications for indoor use or by solar light for outdoor use. Various approaches were considered, and in 2001, a Japanese chemist named Asahi working out of Toyota labs, published a paper in the journal Science on nitrogen doped titanium dioxide materials. Nitrogen doping produced what is commonly called yellow TiO2 (because of, unsurprisingly, its yellow colour!) which showed effective UV and visible light activity. While there is some debate around how the activity is increased, the N-doped TiO2 is shown to have a much greater absorbance in the visible region (extending from a sharp cut off at about 390 nm to a broad cut off at above 500 nm). This subsequently increased the amount of visible light activity the material could absorb, and hence meant that visible light-activated photocatalysis was achievable.

There has been some discussion in the literature on the mechanism on enhancement of nitrogen doping, and the mechanism described here is one put forward by Nakoto (2004) and Irie (2003), and counters Asahi’s original explanation that the N-doping narrowed the gap between the valence band and conduction band of titania. these researchers proposed that the introduction of nitrogen introduced new occupied (i.e. electron rich) orbitals in between the valence band (which are comprised primarily of O-2p orbitals) and conduction band (which are comprised primarily of Ti-3d orbitals). These N-2p orbitals acted as a step up for the electrons in the O-2p orbital, which once populated had now a much smaller jump to make to be promoted into the conduction band.Once this process occurs, electrons from the original valence band can migrate into the mid-band gap energy level, leaving a hole in the valence band, which reacts as described before.

N-doping as explained by Nakoto and Irie. Doping with nitrogen results in a mid-band gap energy level which reduces the energy gap required for charge separation

N-doping as explained by Nakoto and Irie. Doping with nitrogen results in a mid-band gap energy level which reduces the energy gap required for charge separation

Increasing efficiency by incorporation of metal nanoparticles

Given that charge separation requires a great deal of effort, a second theme of research (as well as increasing visible light activity) is to facilitate charge separation. One clever way of doing this is to incorporate noble metal nanoparticles such as silver or gold into the titanium dioxide material. As an example, incorporation of a small amount of silver (1 – 5%) results in increased efficiency in photocatalysis. Silver has a “Fermi level” or electron accepting region at an energy just below the conduction band. Therefore, after light absorption and charge separation, the electron in the conduction band can be effectively trapped by the silver, while the hole oxidises water and forms hydroxyl radicals, without the threat of recombination. Various researchers, including our own work, have shown that there is an optimum amount or “Goldilock’s zone” of silver to add – just enough is needed so that there are silver sites dispersed through the material to rapidly trap electrons, but that too much silver may cover the titanium dioxide and prevent light absorption. In addition, too much silver may mean that the silver acts as a recombination site itself – essentially it will form a bridge between an electron and a hole.

The emission of titanium dioxide (and of similar studies with zinc oxide) can be interpreted as a measure of the recombination efficiency. Studies examining the emission of these metal oxides have demonstrated that the emission intensity reduces on increasing amounts of silver – indicating that the silver is trapping electrons and reducing electron-hole recombination, as indicated in the diagram below.

Incorporation of silver nanoparticles facilitate longer charge separation by trapping photogenerated electrons

Incorporation of silver nanoparticles facilitate longer charge separation by trapping photogenerated electrons

Heterojunctions

A similar strategy to that described above, an a rapidly evolving area, is the idea of incorporating different semiconductors which have different conduction band energy levels. The strategy is as before, trap the electron so the hole has more time to react. A simple example is the anatase-rutile heterojunction. Rutile has a smaller band gap (by about 0.2 eV) to anatase, although their valence band levels are at similar energies. Therefore, in an analogous fashion to the situation with silver, above, charge separation in anatase, followed by electron injection into the rutile conduction band means that there is a hole in the valence band of anatase that can freely oxidise water. It is no coincidence that the industry standard photocatalyst, Degussa P25, has a 75:25 ratio of anatase:rutile (it also has a very small particle size).

Summary

Semiconductor photocatalysis is the utilisation of photogenerated strongly oxidising hydroxyl radicals, which can be applied to a wide range of scenarios, including organic degradation (for pollution remediation) and in organic synthesis. Light induced charge separation, followed by generation of hydroxyl radicals is in the normal course of event reliant on UV light, given the energy gap (band gap) of titanium dioxide. Strategies to enhance the photocatalytic activity include doping to reduce the energy required for charge separation and incorporation of nanoparticles to lengthen the period of charge separation. The size of the materials is also a factor, as for degradation of materials, the pollutant needs to be very near to or adsorbed onto the surface of the semiconductor, and nanoparticulate materials mean that a greater surface area can be exploited.

References

Asahi, R., Morikawa, T., Ohwaki, T., Aoki, K. and Taga, Y., Visible-light photocatalysis in nitrogen-doped titanium oxides, Science, 2001, 294, 269 – 271. Asahi’s paper describing his results on N-TiO2. the work shows irradiation by UV-only and visible-only light, showing the enhancement by N-TiO2 with visible light source.

Bahnemann, D., Photocatalytic water treatment: solar energy applications, Solar Energy, 2004, 77, 445–459. Prof Bahnemann is one of Europe’s most active researchers in this field, and this very readable paper shows how the technology can and is used in solar decontamination technology.

Nakamura R, Tanaka T, and Nakato Y., Mechanism for visible light responses in anodic photocurrents at N-doped TiO2 film electrodes, J. Phys Chem. B., 2004, 108, 10617 – 10620. (See also Irie, H et al, J. Phys Chem. B., 2003, 107, 5483 – 5486). Papers explaining the origin of the hypothesis for the mid-gap energy levels introduced by nitrogen doping.

Seery, M. K., George, R., Floris, P. and Pillai, S. C., Silver doped titanium dioxide nanomaterials for enhanced visible light photocatalysis, J. Photochem. Photobiol A: Chemistry, 2007, 189(2-3), 258 – 263 and Georgekutty, R., Seery, M. K. and Pillai, S. C., A Highly Efficient Ag-ZnO Photocatalyst: Synthesis, Properties and Mechanism, J. Phys. Chem. C, 2008, 112(35), 13563 – 13570. these papers detail the incorporation of silver into titanium and zinc oxides respectively, including some consideration of mechanism.

Origins of Flash Photolysis: George Porter

Flash photolysis revolutionised the science of photochemistry by allowing for rapid (and the definition of that term was era-dependent) monitoring of photochemical intermediates. Since its development in the mid-20th century, flash photolysis has been at the centre of studies of photochemical/physical processes. Developed by Porter, working with Norrish at Cambridge, at the microsecond timescale, the instrumentation has now evolved to the femtosecond timescale – nine orders of magnitude faster over four decades. Porter said in 1975 that he anticipated femtosecond spectroscopy within five years, and it was primarily instrumental issues which delayed his vision. His foresight was eventually realised with the work of Egyptian photophysicist Ahmed Zewail, working at Caltech. This first in a sequence of articles covers the historical development of flash photolysis, we will look in future posts at the progress leading up to Zewail’s development of femtosecond spectroscopy as well as outlining how it is used experimentally to study photochemical intermediates.

1. Development of Early Instrumentation

When Ronald Norrish, Goerge Porter and Manfred Eigen were awarded the Nobel Prize in 1967, for studies of extremely fast chemical reactions, effected by disturbing the equilibrium by means of very short impulses of energy, it was an acknowledgement of their pioneering work in developing apparatus to study microsecond chemical reactions in the microsecond timescale. Eigen’s work inolved using sound waves (a form of pressure) to perturb (or distort) systems, subtly, and Porter, working as a student of Norrish’s at Cambridge, used UV flashes to perturb systems creating electronically excited states. Prior to this development, “fast” reaction kinetics were capable of being studied only on the sub-second time-scale using stopped-flow apparatus, which was developed in the 1920’s. The concept was simple in principle – distort the system at equilibrium using a high-energy flash of light and detect how fast the system restores to equilibrium. The difference here from previous approaches to kinetic analysis was that studies, for example in stopped flow, examined how fast systems approached equilibrium on mixing, and hence were limited by how fast mixing could be effected.

Porter has said that his work for the navy during World War II, as a radar scientist using pulses of electromagnetic radiation was the seed for his ideas at Cambridge when he went to work as Norrish’s graduate student after the war in 1945. Having been sent to get a replacement lamp for a torch for experiments he was conducting to study the CH2 radical (the torch was acting as a continuous light source), Porter saw flash-lamps being manufactured at the Siemen’s factory in Preston, UK and in 1947, introduced the idea of using flash lamps as a pulse of energy to “study transient phenomenon”. The second flash (the true genius of the development), after the burst of light creating the transient state, would essentially photograph the transient phenomenon – so the time scale of the flash was crucial. At the time, millisecond measurement was considered “far beyond direct physical measurement”. Flash photolysis would allow liftetimes 1000 times shorter to be measured by 1950.

The flash lamp used by Porter was a high-intensity pulsed lamp used by the Royal Navy at the time for night-time aerial photography. It was contained in a 1 m long quartz tube (2000 μF charged to 4 kV for those interested in electronics). It could be discharged in 2 ms. The probe flash – a less intense light source which would measure the changes in absorption after the initial flash was 50 microseconds, and both the initial flash (pump) and probe were timed using a timing wheel, which can be seen in the photograph of the original apparatus (to the right of the apparatus) below.

Left: Lord George Porter. Image generously donated by Lady Porter, (c) Lady Porter; used with permission. Right: The first flash photolysis apparatus. From Thrush, Photochem. Photobiol. Sci., 2003, 2, 453–454 - used by permission of the Royal Society of Chemistry - see link below)

Left: Lord George Porter at the time of the development of flash photolysis. Image generously donated by Lady Porter, (c) Lady Porter; used with permission. Right: The first flash photolysis apparatus. From Thrush, Photochem. Photobiol. Sci., 2003, 2, 453–454 - used by permission of the Royal Society of Chemistry - see link below)

2. Early Experiments

Interestingly, the first experiments the apparatus was used in have direct relevance to modern science – the study of hydroxyl radicals in hydrogen-oxygen-nitrogen dioxide systems and in the study of the ClO radical in chlorine-nitrogen-oxygen systems. These species and intermediates generated are at the heart of stratospheric chemistry research today. Early transient absorption spectroscopy experiments (see Windsor article in same issue, referenced below) were on triplet-triplet absorption in polyaromatic hydrocarbons (PAHs), again environmentally relevant species today. These studies looked at the kinetics of decay of the triplet state, in the microsecond timescale, and how they were affected by solvent viscosity, presence of oxygen, etc. These studies formed the backbone of a wide and ever-growing research into organic compounds (including my own on enone-alkene cycloadditions some 40 years later!).

Review

It’s difficult for us now to comprehend the true genius exhibited by Porter in his development of flash photolysis. I think it demonstrates magnificent scientific flair, taking together his previous experience, observance of available instruments parts and an obviously great understanding of chemistry, and combining to develop flash photolysis. The development of the technique revolutionised the fields of kinetics and photochemistry, with implications across a huge variety of fields, including, as we have seen above, stratospheric chemistry and organic photochemistry. Porter has sown the seeds for fast very fast and ultimately ultrafast reaction kinetics, which essentially required faster and faster laser pulses to achieve. By the late 1960’s, nanosecond spectroscopy was feasible.

In the next article on this topic, which will be linked here, we will look at Zewail’s work in developing femtosecond spectroscopy.

References

This article is sourced from various articles, as indicated below:

Van Houten, J. A Century of Chemical Dynamics Traced through the Nobel Prizes: 1967: Eigen, Norrish, and Porter, J. Chem. Educ., 2002, 79(5), 548 – 550. Overview of the development of Flash Photolysis in the context of Nobel Prizes in kinetics generally.

Thrush, B. A., The Genesis of Flash Photolysis, Photochem. Photobiol. Sci., 2003, 2, 453 – 454. Short article on the experimental details, as part of a special issue on George Porter’s work and influence in the area. The journal issue generally shows the scope of flash photolysis in photochemistry research today.

Farago, P., Interview with Sir George Porter, J. Chem. Educ., 1975, 52(11), 703 – 705. Great interview with Porter – what comes across so well is his keen interest in science and in promotion of good science communication. Well worth a  read.

Windsor, M. W., Flash photolysis and triplet states and free radicals in solution, Photochem. Photobiol. Sci., 2003, 2, 455 – 458. Wonderful personal account of Porter’s first student (as I can gather) and his work on the development of triplet-triplet absorption spectroscopy.