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A bright future for sunscreens
Understanding the intrinsic properties of molecules that protect our skin from the harmful rays of the Sun is critical to developing more efficacious sunscreen products. Now, gas-phase spectroscopy and microsolvation studies of model ultraviolet-filter molecules have shown that they may provide a route to developing improved sunscreens.
Vasilios G. Stavros
M
1
ππ*
nπ*
isomerization (few ps)
~20 ns
Cis–trans double bond
UV-B
Degradation
UV-B
1
× Degradation gradat
~3 ps Energy
alignant melanoma is one of the most common cancers in the UK, with skin cancer incidence statistics showing around 13,000 new cases of malignant melanomas in 2011 (ref. 1). This alarmingly large number has meant that there have been increasing efforts towards developing more efficient sunscreens that act as ultraviolet light filters. Given their recognized importance and widespread commercial use, surprisingly little is known about how, after light absorption, these sunscreens disperse highly toxic UV energy in a non-toxic manner at the molecular level. Gleaning insight into such ‘photoprotection’ mechanisms will inevitably assist in developing next-generation sunscreens. Now, writing in the Journal of Physical Chemistry Letters, Wybren Jan Buma and co-workers2 show how the fundamental photochemical properties of common sunscreen constituents control their effectiveness as UV filters. Using gas-phase spectroscopy methods, which provide exquisite insight into the intrinsic properties of isolated molecules, they studied the initial molecule–photon interaction and tracked the subsequent photochemical ‘cascade’ — observing the behaviour of the molecule as it ‘drops’ from a high-energy excited state. They then demonstrate how the addition of just a single water solvent molecule (microsolvation) can dramatically alter the properties of sunscreen constituents. In doing so, they have taken a large step towards suggesting effective means by which to improve the efficacy of commercially available sunscreens. Buma and co-workers chose to study 2-ethylhexyl-4-methoxycinnamate (EHMC), a molecule commonly used as a UV-B (315–280 nm) filter in sunscreens together with a simplified version of EHMC, methyl4-methoxycinnamate (MMC). For both EHMC and MMC, absorption of a UV-B photon results in the promotion of an electron from a bonding π orbital into an antibonding π* orbital, transforming both molecules into an excited singlet ππ* state (1ππ*). The frequency-resolved spectrum for this absorption process in MMC displayed a
Electronic ground state MMC
MMC-H2O
Figure 1 | A schematic of a proposed kinetic scheme for methyl-4-methoxycinnamate (MMC) and MMC–H2O following irradiation with UV-B. The addition of a water molecule reverses the energetic ordering of the 1ππ* and 1nπ* states shown in blue and red, respectively. In so doing, the 1nπ* ‘bottleneck’ in MMC is removed. The photoexcited molecule can thus undergo much faster relaxation back to the electronic ground state, effectively bypassing photodegradation. Insets: molecular structure of s-cis-MMC (left) and ‘microsolvated’ s-cis-MMC (right). Figure reproduced with permission from ref. 2, © 2014 ACS; water ripple © PhotoDisc/Getty Images/Don Farrall.
dense manifold of transitions to vibrational levels in the excited state, which they were able to attribute to two conformers — the s-cis (shown in Fig. 1) and s-trans conformers. Using these MMC studies as a benchmark, they were then able to assign the excitation spectrum for EHMC, once again to the s-cis and s-trans conformers. Most significantly though, the spectral linewidths from the excitation spectra provide information about the lifetimes of the states through the energy–time uncertainty principle, revealing picosecond lifetimes of the initially excited 1ππ* states
NATURE CHEMISTRY | VOL 6 | NOVEMBER 2014 | www.nature.com/naturechemistry
© 2014 Macmillan Publishers Limited. All rights reserved
in both MMC and EHMC. However, this result appeared to be in stark contrast to their time-resolved measurements, which reported longer excited-state lifetimes on the order of nanoseconds. The highly complementary frequencyand time-resolved studies enabled Buma and co-workers to propose that after excitation of a 1ππ* state in MMC and EHMC, nonradiative internal conversion then causes transformation into a weakly absorbing (optically dark) excited 1nπ* state, within a few picoseconds. It is this 1nπ* state that is responsible for the longer nanosecond 955
news & views lifetime. The kinetic scheme is summarized by the sketch shown in Fig. 1 for MMC. Intriguingly, such lengthy excited-state lifetimes run counterintuitively to what one anticipates from a sunscreen; prolonged decay times back to the electronic ground state increases the likelihood of competing (and potentially harmful) reaction pathways, such as radical formation. This is in line with previous studies, which have shown that EHMC decomposes on exposure to UV radiation3. In contrast, and in concordance with what one intuitively requires, naturally occurring biological sunscreens, such as eumelanins (the brown pigment found in skin), have excited-state lifetimes that are orders of magnitude shorter 4. The question that then arises is: can the efficacy of EHMC as a sunscreen constituent be improved by learning from nature? Buma and co-workers sought ways to address this question. Using insight from organic chemistry, where polar solvents are known to stabilise 1ππ* states while also destabilise 1nπ* states5, they were able to effectively remove the bottleneck created by the long-lived 1nπ* state. They achieved this by extending their measurements and microsolvating MMC, generating clusters of MMC with a single water molecule attached. Linewidth analysis of the frequency-resolved excitation spectrum of MMC–H2O revealed that the lifetime of the 1ππ* state was still a few picoseconds. This was in contrast to the time-resolved measurements, which now showed the excited-state lifetime of MMC–H2O to be faster than the time resolution of their experiment. This led the
956
authors to propose that unlike MMC, which undergoes internal conversion from the short-lived 1ππ* state (picoseconds) to the long-lived 1nπ* state (nanoseconds), MMC– H2O undergoes rapid internal conversion from the 1ππ* state to the electronic ground state, mediated in part by cis–trans double bond isomerization. Akin to biological sunscreens, the potentially toxic energy localized in electronically excited states is thus converted to vibrational motion (heat) in the electronic ground state, which can then be harmlessly dissipated into the surrounding solvent. The drastic change in the excited-state lifetime of MMC following complexation with water is a tell-tale signifier of the influence of intramolecular solute–solvent interactions on electronic structure; the ability to manipulate electronic structure through solvent polarity could, as Buma and co-workers point out, offer elegant means to influence the efficacy of sunscreen constituents, such as EHMC. A salient point emerging from these studies is the importance of ‘bottom-up’ methodologies. With reference to the present studies, such a molecular-level understanding of photoprotection and factors that inhibit and promote this process (for example, solvation) would not be possible otherwise, adding further gravitas to the importance of such gas-phase studies6. These coup de maître measurements by Buma and co-workers offer insight into the field of photoprotection, with direct insight into the intrinsic properties of biologically important molecules and specifically how
we can potentially tailor their electronic structure for commercial use. Moving forward, there is the tantalizing prospect of triggering new and exciting avenues of research; for example, experiments that target the influence of increasing cluster size and the role of chemical substitution7. Perhaps more importantly, these gas-phase studies offer detailed dynamical insight, which can be used to inform measurements carried out in the more complex and biologically relevant condensed-phase environment. Steps have already been taken along these lines8 and much larger steps are still to follow; Buma and co-workers’ investigations on the photoprotection mechanisms of molecular sunscreens have thrown down the gauntlet to both experimentalists and theorists seeking to apply fundamental research to advance healthcare technologies. ❐ Vasilios G. Stavros is in the Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK. e-mail: [email protected] References
1. www.cancerresearchuk.org 2. Tan, E. M. M., Hilbers, M. & Buma, W. J. J. Phys. Chem. Lett. 5, 2464–2468 (2014). 3. Butt, S. T. & Christensen, T. Radiat. Prot. Dosim. 91, 283−286 (2000). 4. Nofsinger, J. B., Ye, T. & Simon, J. D. J. Phys. Chem. B 105, 2864–2866 (2001). 5. Williams, D. H. & Fleming, I. Spectroscopic Methods in Organic Chemistry 6th edn (McGraw-Hill Education, 2008). 6. Verlet, J. R. R. Chem. Soc. Rev. 37, 505–517 (2008). 7. Karsili, T. N. V. et al. J. Phys. Chem. A http://dx.doi.org/10.1021/ jp507282d (2014). 8. Harris, S. J. et al. Phys. Chem. Chem. Phys. 15, 6567–6582 (2013).
NATURE CHEMISTRY | VOL 6 | NOVEMBER 2014 | www.nature.com/naturechemistry
© 2014 Macmillan Publishers Limited. All rights reserved
A bright future for sunscreens
Understanding the intrinsic properties of molecules that protect our skin from the harmful rays of the Sun is critical to developing more efficacious sunscreen products. Now, gas-phase spectroscopy and microsolvation studies of model ultraviolet-filter molecules have shown that they may provide a route to developing improved sunscreens.
Vasilios G. Stavros
M
1
ππ*
nπ*
isomerization (few ps)
~20 ns
Cis–trans double bond
UV-B
Degradation
UV-B
1
× Degradation gradat
~3 ps Energy
alignant melanoma is one of the most common cancers in the UK, with skin cancer incidence statistics showing around 13,000 new cases of malignant melanomas in 2011 (ref. 1). This alarmingly large number has meant that there have been increasing efforts towards developing more efficient sunscreens that act as ultraviolet light filters. Given their recognized importance and widespread commercial use, surprisingly little is known about how, after light absorption, these sunscreens disperse highly toxic UV energy in a non-toxic manner at the molecular level. Gleaning insight into such ‘photoprotection’ mechanisms will inevitably assist in developing next-generation sunscreens. Now, writing in the Journal of Physical Chemistry Letters, Wybren Jan Buma and co-workers2 show how the fundamental photochemical properties of common sunscreen constituents control their effectiveness as UV filters. Using gas-phase spectroscopy methods, which provide exquisite insight into the intrinsic properties of isolated molecules, they studied the initial molecule–photon interaction and tracked the subsequent photochemical ‘cascade’ — observing the behaviour of the molecule as it ‘drops’ from a high-energy excited state. They then demonstrate how the addition of just a single water solvent molecule (microsolvation) can dramatically alter the properties of sunscreen constituents. In doing so, they have taken a large step towards suggesting effective means by which to improve the efficacy of commercially available sunscreens. Buma and co-workers chose to study 2-ethylhexyl-4-methoxycinnamate (EHMC), a molecule commonly used as a UV-B (315–280 nm) filter in sunscreens together with a simplified version of EHMC, methyl4-methoxycinnamate (MMC). For both EHMC and MMC, absorption of a UV-B photon results in the promotion of an electron from a bonding π orbital into an antibonding π* orbital, transforming both molecules into an excited singlet ππ* state (1ππ*). The frequency-resolved spectrum for this absorption process in MMC displayed a
Electronic ground state MMC
MMC-H2O
Figure 1 | A schematic of a proposed kinetic scheme for methyl-4-methoxycinnamate (MMC) and MMC–H2O following irradiation with UV-B. The addition of a water molecule reverses the energetic ordering of the 1ππ* and 1nπ* states shown in blue and red, respectively. In so doing, the 1nπ* ‘bottleneck’ in MMC is removed. The photoexcited molecule can thus undergo much faster relaxation back to the electronic ground state, effectively bypassing photodegradation. Insets: molecular structure of s-cis-MMC (left) and ‘microsolvated’ s-cis-MMC (right). Figure reproduced with permission from ref. 2, © 2014 ACS; water ripple © PhotoDisc/Getty Images/Don Farrall.
dense manifold of transitions to vibrational levels in the excited state, which they were able to attribute to two conformers — the s-cis (shown in Fig. 1) and s-trans conformers. Using these MMC studies as a benchmark, they were then able to assign the excitation spectrum for EHMC, once again to the s-cis and s-trans conformers. Most significantly though, the spectral linewidths from the excitation spectra provide information about the lifetimes of the states through the energy–time uncertainty principle, revealing picosecond lifetimes of the initially excited 1ππ* states
NATURE CHEMISTRY | VOL 6 | NOVEMBER 2014 | www.nature.com/naturechemistry
© 2014 Macmillan Publishers Limited. All rights reserved
in both MMC and EHMC. However, this result appeared to be in stark contrast to their time-resolved measurements, which reported longer excited-state lifetimes on the order of nanoseconds. The highly complementary frequencyand time-resolved studies enabled Buma and co-workers to propose that after excitation of a 1ππ* state in MMC and EHMC, nonradiative internal conversion then causes transformation into a weakly absorbing (optically dark) excited 1nπ* state, within a few picoseconds. It is this 1nπ* state that is responsible for the longer nanosecond 955
news & views lifetime. The kinetic scheme is summarized by the sketch shown in Fig. 1 for MMC. Intriguingly, such lengthy excited-state lifetimes run counterintuitively to what one anticipates from a sunscreen; prolonged decay times back to the electronic ground state increases the likelihood of competing (and potentially harmful) reaction pathways, such as radical formation. This is in line with previous studies, which have shown that EHMC decomposes on exposure to UV radiation3. In contrast, and in concordance with what one intuitively requires, naturally occurring biological sunscreens, such as eumelanins (the brown pigment found in skin), have excited-state lifetimes that are orders of magnitude shorter 4. The question that then arises is: can the efficacy of EHMC as a sunscreen constituent be improved by learning from nature? Buma and co-workers sought ways to address this question. Using insight from organic chemistry, where polar solvents are known to stabilise 1ππ* states while also destabilise 1nπ* states5, they were able to effectively remove the bottleneck created by the long-lived 1nπ* state. They achieved this by extending their measurements and microsolvating MMC, generating clusters of MMC with a single water molecule attached. Linewidth analysis of the frequency-resolved excitation spectrum of MMC–H2O revealed that the lifetime of the 1ππ* state was still a few picoseconds. This was in contrast to the time-resolved measurements, which now showed the excited-state lifetime of MMC–H2O to be faster than the time resolution of their experiment. This led the
956
authors to propose that unlike MMC, which undergoes internal conversion from the short-lived 1ππ* state (picoseconds) to the long-lived 1nπ* state (nanoseconds), MMC– H2O undergoes rapid internal conversion from the 1ππ* state to the electronic ground state, mediated in part by cis–trans double bond isomerization. Akin to biological sunscreens, the potentially toxic energy localized in electronically excited states is thus converted to vibrational motion (heat) in the electronic ground state, which can then be harmlessly dissipated into the surrounding solvent. The drastic change in the excited-state lifetime of MMC following complexation with water is a tell-tale signifier of the influence of intramolecular solute–solvent interactions on electronic structure; the ability to manipulate electronic structure through solvent polarity could, as Buma and co-workers point out, offer elegant means to influence the efficacy of sunscreen constituents, such as EHMC. A salient point emerging from these studies is the importance of ‘bottom-up’ methodologies. With reference to the present studies, such a molecular-level understanding of photoprotection and factors that inhibit and promote this process (for example, solvation) would not be possible otherwise, adding further gravitas to the importance of such gas-phase studies6. These coup de maître measurements by Buma and co-workers offer insight into the field of photoprotection, with direct insight into the intrinsic properties of biologically important molecules and specifically how
we can potentially tailor their electronic structure for commercial use. Moving forward, there is the tantalizing prospect of triggering new and exciting avenues of research; for example, experiments that target the influence of increasing cluster size and the role of chemical substitution7. Perhaps more importantly, these gas-phase studies offer detailed dynamical insight, which can be used to inform measurements carried out in the more complex and biologically relevant condensed-phase environment. Steps have already been taken along these lines8 and much larger steps are still to follow; Buma and co-workers’ investigations on the photoprotection mechanisms of molecular sunscreens have thrown down the gauntlet to both experimentalists and theorists seeking to apply fundamental research to advance healthcare technologies. ❐ Vasilios G. Stavros is in the Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK. e-mail: [email protected] References
1. www.cancerresearchuk.org 2. Tan, E. M. M., Hilbers, M. & Buma, W. J. J. Phys. Chem. Lett. 5, 2464–2468 (2014). 3. Butt, S. T. & Christensen, T. Radiat. Prot. Dosim. 91, 283−286 (2000). 4. Nofsinger, J. B., Ye, T. & Simon, J. D. J. Phys. Chem. B 105, 2864–2866 (2001). 5. Williams, D. H. & Fleming, I. Spectroscopic Methods in Organic Chemistry 6th edn (McGraw-Hill Education, 2008). 6. Verlet, J. R. R. Chem. Soc. Rev. 37, 505–517 (2008). 7. Karsili, T. N. V. et al. J. Phys. Chem. A http://dx.doi.org/10.1021/ jp507282d (2014). 8. Harris, S. J. et al. Phys. Chem. Chem. Phys. 15, 6567–6582 (2013).
NATURE CHEMISTRY | VOL 6 | NOVEMBER 2014 | www.nature.com/naturechemistry
© 2014 Macmillan Publishers Limited. All rights reserved
