Photochemical and photophysical properties of sunscreens

92001 Elsevier Science B.V. All rights reserved

495

Sun Protection in Man

EU. Giacomoni, editor

Chapter 26

Photochemical and photophysical properties of sunscreens Ann Cantrell, David J. McGarvey and T. George Truscott Table of contents Abstract .....................................................................

497

26.1 26.2

Introduction ............................................................ Organic systems ........................................................

497 499

26.2.1 A m i n o b e n z o a t e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

499

26.2.2 A n t h r a n i l a t e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

502

26.2.3 B e n z o p h e n o n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

504

26.2.4 B e n z y l i d e n e c a m p h o r s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

505

26.2.5 C i n n a m a t e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26.2.6 D i b e n z o y l m e t h a n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

508 509

26.2.7 S a l i c y l a t e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

512

26.3

26.2.8 M i s c e l l a n e o u s o r g a n i c s u n s c r e e n s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Inorganic systems ......................................................

512 513

26.4

26.3.1 T i t a n i u m d i o x i d e and zinc o x i d e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary ...............................................................

513 516

References ...................................................................

516

PHOTOCHEMICAL AND PHOTOPHYSICAL PROPERTIES

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Abstract Topical sunscreens provide a means of sun protection and function by the absorption of light effecting an electronic excitation of the sunscreen molecule (from its ground state to a first excited singlet state). Effective sunscreens are those that absorb strongly in the appropriate UV region, display good photostability and exhibit minor spectral modifications upon exposure to UV radiation and thermally dissipate the absorbed energy harmlessly. The most effective deactivation routes are internal conversion, vibrational relaxation and photoisomerisation. However, organic UV absorbers have the potential to form relatively long-lived triplet states, which can stimulate singlet oxygen production, effect transformations in biological substrates, such as thymine or in constituents of sunscreen formulations. This chapter is concerned with a critical assessment of the photochemical and photophysical properties of a range of commercially available organic (UVA and UVB) and inorganic sunscreens with respect to their efficacy and suitability as common sunscreen ingredients. We focus on the positive and negative attributes of the photochemical properties of sunscreens and consider the impact of published findings on sunscreen manufacturers and the development of new sunscreen agents. We conclude that many organic sunscreens function by photoisomerisation, where isomeric mixtures serve as the major sun protection components. However, a number of sunscreens also form triplet states and singlet oxygen. Furthermore, inorganic sunscreens such as titanium dioxide and zinc oxide are known to degrade organic materials and produce hydroxyl radicals, although this is somewhat overcome by the use of surface treatment. Photoactivity testing of inorganic sunscreens is at an early stage of development and further work is required to achieve suitable protocols.

26.1 Introduction The effects of ultra-violet radiation, UVR (both UVA and UVB) on human health are well documented and include photoaging [1], immunosuppression [2] and cancer (squamous/basal cell carcinoma and malignant melanoma) [3]. Human skin has inherent protection from UVR through urocanic acid (the degradation product of histidine) and the naturally occurring eumelanin that arises from melanogenesis [4], as well as the other systems described in this monograph. However, these systems are not infallible and vary in their effectiveness between skin types. The increased incidence in sun-related illnesses has stimulated the development of additional protection measures and specifically the production of topically applied organic and inorganic sunscreens, the first ones being used as early as the 1920s [5]. This chapter is concerned only with systems that are employed commercially. Sunscreens may be classed as either UVA or UVB absorbers according to their spectral profiles, although some absorb in both regions. Sunscreens function through a combination of absorption, reflection and scattering of UVR, thus preventing the UVR from impinging on the surface of the skin. It is necessary, however, for the sunscreens to dissipate the excess energy harmlessly and there are various pathways through which this is achieved.

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VR o} L G) r (l)

im m

s=

~ 4-1

ISC

c:

........

O

A SQ

1 ,,~r A~ ~ ,,

F

q

If'

-w,-

T2 11

" ~ 1 ~

T1

.....

I~1

orlO2

~r

RADIATIVE TRANSITIONS"

NON-RADIATIVE TRANSITIONS:

A = ABSORI:rrlON F = FLUORESCENCE

IC = INTERNALCONVERSION ISC = INTERSYSTEMCROSSING

P = PHOSPHORESCENCE

VR = VIBRATIONAL RELAXATION

I = ISOMERISATION(INCLUDES TAUTOMERISATION ETC)

F i g u r e 1. Modified Jablonski diagram.

The electronic energy levels of organic molecules and the principal intramolecular photophysical processes (processes that do not result in chemical change) are often represented on a Jablonski diagram (Fig. 1). Photophysical and photochemical phenomena in organic molecules involve (predominantly) the first excited singlet ($1) and triplet (T1) states. The photophysical deactivation routes (given in Fig. 1) from $1 and/or T1 include radiative processes (straight arrows, fluorescence and phosphorescence), and non-radiative processes (wavy arrows, vibrational relaxation, internal conversion and intersystem crossing). Triplet states are generally much longer-lived than singlet states, and consequently triplet states are generally more susceptible to quenching by intermolecular processes. However, triplet state formation is dependent on ISC from $1, and hence measurements of the efficiency of triplet state formation (the triplet state quantum yield, ~bT) and the triplet state lifetime (rT) are important for new sunscreens. Excited states are quenched by molecular oxygen and this may lead to formation of a reactive excited state of oxygen, singlet oxygen (ground state oxygen is a triplet state, Scheme 1). S~ + 3 0 2

~

T1

T1 +

~

S0 + 1 0 ~

302

TI+IQ

-~- 1 0 ~

__~ s0+3Q*

S c h e m e 1. Q = quencher, So = ground state species, T1 = triplet excited state.

Photochemical processes include photoisomerisation, photofragmentation and other phototransformation reactions, which may arise from either singlet or triplet excited states. It is desirable for sunscreens to exhibit strong and broad absorption in the appropriate UV region (i.e. possess a large molar absorption coefficient) and to degrade the

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499

Table 1. Some methods employed to study photo-properties of molecules Parameters

Method

rT q~, ~isom ET

Laser flash photolysis, pulse radiolysis Laser flash photolysis Phosphorescence, energy transfer, oxygen perturbation of So - T1 absorption Laser flash photolysis- near I.R. luminescence, chemical traps

4'A

absorbed energy rapidly and harmlessly. Sunscreens should be photostable, such that modifications to the absorption spectrum that result from UV exposure are moderate and that minimal loss of protective power occurs. Furthermore, excited state deactivation of the sunscreen should be rapid (sub-nanosecond or faster) and the triplet state energy level (Ev) low, therefore, minimising the possibility of sensitising thymine triplet states (which can lead to the formation of thymine dimers [6]), or causing other photosensitised transformations within the sunscreen formulation or on/in the skin. Methods for determining photochemical/physical parameters of molecules are summarised in Table 1. Sunscreens generally do not possess all of the optimum optical and photochemical characteristics described above and many may fall short in several areas. It is therefore prudent that fundamental photochemical studies are carried out on existing sunscreens and on those at the developmental stage, in order to reveal the detailed photophysical and photochemical behaviour that underlies the observed photostability of sunscreens and to reveal any undesirable attributes that have the potential to cause damage to human skin or to other constituents in sunscreen formulations.

26.2 Organic systems The range of organic sunscreens is considerable, and tailored substitution of the basic molecular templates affords fine-tuning of spectral (and other) properties. The sunscreens are broadly categorised according to their structures and include derivatives of aminobenzoates (I, II), anthranilates (III, IV), benzophenones (V, VI, VII), benzylidene camphors (VIII, IX), cinnamates (X, XI), dibenzoylmethanes (XII, XIII) and salicylates (XIV) [7,8]. Each group of organic sunscreen is discussed separately (Fig. 2). Fig. 3 summarises molar absorption coefficient data (at)~max) for common organic UVA and UVB sunscreens available commercially in Europe and/or the USA.

26.2.1 Aminobenzoates p-Aminobenzoic acid (PABA) was one of the first UVB sunscreens to be used and has received (along with its derivatives) considerable adverse publicity. This stems from studies, showing that PABA derivatives cause adverse skin reactions and that their photochemical properties do not meet some of the most important criteria for an ideal sunscreen. In 1982, in vitro studies on PABA revealed potentially hazardous

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H3C~N"/CH3

NH2

~

I

II III

o.

o

OH O

i v

OH

vI

~

IV

,co ,C, oc, OH O

~

O H 3 C O ~'" ~

OH3 0

O 0

sO3H

IX

o

\~(

OH

VII

HO3S ~ VIII

O~..,~CH3

~ O

OH

OH ..~ OCH3

o

il XIV

H

Figure 2. Structures of some UVA and UVB sunscreens: I -- p-aminobenzoic acid (PABA)" II octyldimethylaminobenzoate (OD-PABA); III = menthyl anthranilate (MA); IV = homomenthyl anthranilate; V = 2-hydroxy-4-methoxybenzophenone (HM-BZP); VI = 2,2',4,4'-tetrahydroxybenzophenone (Benzophenone 2) and VII = 2,2'-dihydroxy-4,4'-dimethoxybenzophenone (Benzophenone 6); VIII 3-4'-methylbenzylidene camphor (MBC); IX -- terephthalylidenedicamphor sulphonic acid (TPDC-SA); X = 2-ethylhexyl-p-methoxycinnamate (2-EHMC); XI = 2-ethylhexyl-2-cyano-3,3-diphenyl-2-propanoate (2-EHCDP); XII -- 4-isopropyldibenzoylmethane (I-DBM) and XIII = 4-tert-butyl-4'-methoxydibenzoylmethane (BM-DBM); XIV = general salicylate structure; XV = 2-phenylbenzimidazole-5-sulphonic acid (PBSA).

PHOTOCHEMICAL AND PHOTOPHYSICAL PROPERTIES

501

Figure 3. Molar absorption coefficients (6max) and absorption maxima (~-max)of various sunscreens.

effects through its ability to photosensitise formation of thymine dimers in cultured human cells [13]. The PABA derivative, octyldimethyl-p-aminobenzoate (OD-PABA, tradename Padimate-O) was also subsequently deemed undesirable as a sunscreen ingredient due to its structural similarity to a radical initiator used for polymerisation, ethyl-4-dimethylaminobenzoate [14], although OD-PABA is still in use today. The main concerns regarding aminobenzoates are their photosensitising abilities. PABA forms various photoproducts derived from free radical intermediates [15,16], produces singlet oxygen [17,18] and binds to DNA and its free bases in aqueous solution leading to formation of DNA photoproducts [19]. OD-PABA is mutagenic and has been shown to cause mutations in yeast cells and to damage DNA following simulated sunlight exposure [20]. In a recent paper [21], OD-PABA was shown to increase strand breaks in DNA when human keratinocytes were exposed to the sunscreen in vitro (simulating its diffusion through the skin) and irradiated with UV-light. However, when a sunscreen formulation (SPF 15 containing OD-PABA, 2-ethylhexylmethoxycinnamate and 2-hydroxy-4-methoxybenzophenone) was irradiated but not in contact with the cells, a reduction in DNA photodamage was observed. Both sunscreens possess strong absorption in the UVB, with maxima at 286 nm for PABA and 309 nm for OD-PABA (Fig. 4). Allen et al. [17] showed that under steady-state irradiation conditions, PABA exhibited a faster rate of formation of singlet oxygen than the other sunscreens studied and this was proposed to be related to reported photoallergic reactions. They quantified singlet oxygen formation by monitoring consumption of furfuryl alcohol (FFA), an established singlet oxygen trap, following illumination of aqueous solutions of various sunscreens using a 1000 W xenon arc lamp. Amongst the sunscreens examined by Allen et al., PABA was found to be the most efficient sensitiser of singlet oxygen under the steady state irradiation conditions employed (given a relative rate of formation of singlet oxygen of 1). OD-PABA was significantly lower (by an order of magnitude, 0.096). These studies involved steady-state irradiation over long periods of time (from

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A. CANTRELL ET AL.

Figure 4. Absorption spectra of (i) PABA and (ii) OD-PABAin ethanol.

80 min for PABA to 400 min for the other sunscreens). Hence, singlet oxygen production may not be solely derived from the starting material, but could also be sensitised by photoproducts. Hill observed triplet state formation from OD-PABA via LFP, and q~r was estimated to be close to 0.1. The singlet oxygen quantum yields of OD-PABA and PABA were also determined (via a steady-state method) as 0.018 and 0.0029, respectively [10]. In addition, studies have shown that PABA is able to sensitise formation of cyclobutane thymine dimers in vitro and to form DNA-sunscreen adducts following UVA irradiation [13,19]. PABA is now considered potentially carcinogenic. However, other studies have shown that PABA is an effective sunscreen agent [22,23]. Furthermore, Sano et al. proposed that PABA exerts some of its positive effects via scavenging of reactive oxygen species. They showed that PABA reacts with hypochlorite (HOC1), scavenges OH" and quenches singlet oxygen (kq ~ 1010 M -1 s -1) [24]. Douarre et al. showed that the ester derivative of PABA, 2-ethylhexyl p-aminobenzoic acid (PAB) exhibits an extremely low quantum yield of photodegradation (-~10 -4) following irradiation at 302 nm in methanol. This was determined via both HPLC and UV-visible spectrophotometry. They point out that the photoproducts possess very similar absorption spectra to the starting material. In the presence of diacetyl (which forms radicals) the degradation quantum yield increases by a factor of 100-1000, and the presence of oxygen is necessary to effect photodegradation [25]. The undesirable photochemical properties of aminobenzoates have led to adverse publicity for their use as sunscreen ingredients, despite the protection against UV exposure that they exhibit. There is considerable controversy regarding the safety of sunscreens, involving conflicting evidence of in vitro and in vivo studies and readers are referred to the recent review by Gasparro et al., which discusses such issues [5].

26.2.2 Anthranilates

Anthranilates are ortho aminobenzoates that possess electron-donating groups. Menthyl anthranilate (MA) is a UVA filter, which has an absorption maximum at 338 nm in

PHOTOCHEMICAL AND PHOTOPHYSICAL PROPERTIES

503

ethanol and a comparatively low molar absorption coefficient of 5800 M -1 cm -1. A LFP study of the photophysical properties of this molecule was reported recently [9]. The authors observed that the triplet state possesses a relatively long-lifetime in several solvents (26 Ixs in ethanol, 122 txs in acetonitrile and 200 Ixs in toluene). In all solvents studied, efficient quenching of the anthranilate triplet state by molecular oxygen was observed, with a second-order quenching rate constant of 108-109 M -1 s -1. The authors demonstrated that MA produces singlet oxygen (via direct luminescence detection), with a quantum efficiency of 0.09-0.12, dependent on solvent. The authors also suggest that the triplet state is formed in a commercial sunscreen formulation, based on their observation of triplet states in various solvents (and not from direct evidence within a commercial product). The triplet state energy of MA was reported to be 69 kcal mol -~ from phosphorescence measurements, although this is subject to some uncertainty as the spectrum is broad, featureless and the position of the (0,0) transition (which corresponds to the triplet energy level) is not clear. The authors do not give an indication of the uncertainty, which may be important since the triplet state energy level is close to that of the thymine triplet state (75 kcal mol-~). MA is also highly fluorescent, with a similar quantum yield of fluorescence to its parent compound, anthranilic acid of -~0.6 [26]. The fluorescence spectrum exhibits a peak at ~400 nm in solution and in a commercial sunscreen system. The fluorescence lifetime was found to be ~5 ns. Fig. 5 gives the absorption and fluorescence spectra of MA in ethanol. The authors point out that there are two interfaces on protected skin, the air-sunscreen and sunscreen-skin interfaces. Due to the differing refractive indices at these interfaces (a larger refractive index difference for the sunscreen-air interface), some emitted light will not escape and the authors suggest that internal reflection of emitted light will occur, which may actually increase the amount of light (of wavelengths 370 to 400 nm) reaching the surface of the skin.

3

..................................................................................................................................................................................... 8

2.5 6 2

)

p.

e

0 m J~

5==

1.5

3~


2,~ 0.5

1

0 ................ 200

0 250

300

350

400

450

500

550

Wavelength/nm

Figure 5. (a) The UV-Visible absorption spectrum of MA in ethanol (1 • 10 -4 M). (b) Corrected fluorescence emission spectrum of MA in ethanol (2 x l0 -5 M), ,kex = 340 nm. (c) The corrected fluorescence excitation spectrum of MA in ethanol (2 x 10 -5 M), ~-em = 405 nm. (d) The delayed fluorescence spectrum of MA in ethanol following 355 nm laser excitation of a degassed solution.

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A. C ANTRELL ET AL.

26.2.3 Benzophenones This category of sunscreen comprises a variety of ortho substituted benzophenones with electron-donating groups that lead to increased electron delocalisation. The spectrum of benzophenone (given in Fig. 6A) consists of a r~-~* transition at 250 nm and a much weaker (e ~ 102 M -1 cm -1) n-~* transition at 350 nm, which is not shown. The spectra of benzophenone derivatives used as sunscreens (Fig. 6B), however, are shifted (to ~325 nm) [7]. The principal benzophenone sunscreen in current use is 2hydroxy-4-methoxybenzophenone (HM-BZP, its tradenames include Benzophenone-3 and Oxybenzone). A drawback with these filters is their comparatively low absorption coefficients (only 9400 M -1 cm -1 at 325 nm for HM-BZP) and thus they do not afford high sun protection factors (SPF) at low to moderate concentrations. Also they offer only limited protection at longer UVA wavelengths. There have been few reports on the photochemistry of benzophenone-based sunscreens although there are reports that they exhibit good photostability [27,28]. Indeed, Deflandre and Lang showed that HM-BZP exhibited only a 1% loss of absorbance (at 320 nm) following one hour of irradiation with a 250 W xenon arc lamp (using a 320 nm cut-off filter) in a model emulsion sample [27]. Furthermore, Tarras-Wahlberg et al. showed that the UV spectrum of HM-BZP and 2-Hydroxy-4-methoxy-4'-methylbenzophenone in petroleum jelly was stable to both UVA and UVB radiation [28]. The benzophenone sunscreens form strong intramolecular hydrogen bonds between the carbonyl oxygen atom and the hydrogen atom of the ortho hydroxyl group, which stabilise the molecule and extend the conjugation of the chromophore. Of course, there have been many photochemical studies of carbonyl compounds and early work by Porter and Suppan led to an understanding of the photoreactivity of benzophenone and its derivatives [29,30]. Benzophenone undergoes efficient ISC to form the lowest excited triplet state, from which many photochemical reactions proceed, including H-abstraction to form the ketyl radical: 3BZP* + RH --+ BZPH" + R"

Figure 6. Absorptionspectra of benzophenone (A) in ethanol (~.max = 251 nm, the weak n-~t* transition at ~350 nm is not shown) and HM-BZPin ethanol (B).

PHOTOCHEMICAL AND PHOTOPHYSICAL PROPERTIES

505

The photoreactivity of benzophenone derivatives is dependent on the nature and position of substituents (which affect the electronic distribution within the lowest triplet state, these may be n-rt* or rt-rt* states). Porter and Suppan first studied a variety of benzophenone derivatives including halogenated, amino and hydroxylated substituents and showed that n-rt* states are more reactive than rt-rt* states [29]. The principal photochemical reactions of carbonyl compounds are well documented and include a-cleavage, intra- and intermolecular hydrogen abstraction.

26.2.4 Benzylidene camphors 3,4'-Methylbenzylidene camphor (MBC, also known, for example, as Parsol 5000 and Eusolex 6300) is a UVB sunscreen and is only authorised for use in Europe at present. It has a large molar absorption coefficient of 24,500 M-1 cm-1 at 300 nm. Terephthalylidene dicamphor sulphonic acid (TPDC-SA, Mexoryl | SX) is a relatively new sunscreen (introduced to the European market in 1993) and is a derivative of MBC. Its extended conjugation shifts the absorption maximum to 345 nm and it is categorised as a hydro-soluble UVA sunscreen with 8max of 47,000 M -1 cm -1 [12]. Fig. 7 shows the absorption spectra of TPDC-SA and MBC in ethanol. Fig. 8 shows the spectrum for a commercial sunscreen (SPF 6) which contains the UVA sunscreens TPDC-SA, BM-DBM, the UVB sunscreen, 2-EHCDP and titanium dioxide. The shoulder of the BM-DBM absorption band is visible at ~380 nm. The camphor sunscreens undergo photo-induced reversible trans-cis isomerisation [31]. Beck et al. irradiated various derivatives of benzylidene camphor (BC) in cyclohexane using a 250 W xenon arc lamp and a 320 nm filter. These workers reported a shift in the absorption spectrum to longer wavelengths after 30 s irradiation but further irradiation caused no subsequent changes in the spectral profile, i.e. the photostationary mixture is photostable. The quantum yield for trans to cis isomerisation of BC was also determined and found to be wavelength dependent (from 0.13 at 287 nm to 0.3 at 370 nm) but independent of concentration, solvent and the presence of oxygen. The quantum yield for photoisomerisation of TPDC-SA has not yet been

Figure 7.

Absorption spectra of TPDCSA (~,2 • 10 -5 M) (A) and of 5 • 10 -5 M MBC (B) in ethanol.

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A. C ANTRELL ET AL.

Figure 8. Absorption spectrum of Ambre-Solaire Moisturising Tanning Milk SPF 6, 1 Ixl cm -2 loaded onto a 25 cm 2 quartz plate.

Figure 9. Absorption spectra of an aqueous solution of TPDC-SA (~2 • 10 -5 M) following UVA irradiation using a 40 W Philips fluorescent lamp (total energy ,-~24 J cm -2) [32].

reported. Fig. 9 shows the absorption spectra of TPDC-SA following UV irradiation and Fig. 10 illustrates photoisomerisation of TPDC-SA. BCs have been shown to exhibit good photostability and Beck et al. found that the quantum yield of photodegradation for many BCs was ~ 10-4 [31]. Deflandre and Lang [27] studied various BC derivatives, including MBC, and determined the percentage

O

h\ o

~E

H

O

3 O

Figure 10. Photoisomerisation process of TPDC-SA.

S Z--E

~ t, ~SO3H

PHOTOCHEMICAL AND PHOTOPHYSICAL PROPERTIES

507

loss of absorbance in an emulsion sample. They showed that the BCs gave only a 1-2.4% loss compared with the DBMs, which showed 40% and 36% loss for I-DBM and BM-DBM, respectively. More recently Tarras-Wahlberg et al. [28] demonstrated the photostability of these molecules and the maintenance of their UV spectral profiles following irradiation. Indeed the protection afforded by the camphor sunscreens is due to the photostationary equilibrium of Z/E isomers, the Z-E isomer displaying a slightly modified absorption profile to that of the E - E isomer of TPDC-SA (see in Fig. 9). Energy transfer from a triplet state donor molecule can also induce isomerisation and hence the isomerisation process can take place from both the singlet and triplet states of these molecules. The quantum yield of isomerisation for benzylidene camphor photosensitised by benzophenone was reported by Beck et al. to be wavelength dependent with a value of ~0.4 following 365 nm irradiation in chloroform [33]. However, other processes may also take place, for example TPDC-SA exhibits weak fluorescence in ethanol and undergoes intersystem crossing (4~r ~ 0.1) to produce the triplet state with a solvent-dependent lifetime that varies from 50 ns in ethanol to 120 ns in acetonitrile. The triplet state is quenched by molecular oxygen to produce singlet oxygen, with a limiting quantum yield (in the event of complete scavenging by oxygen) of ~0.09 in acetonitrile [34]. Furthermore, the triplet state of TPDC-SA has also been detected in a commercial sunscreen preparation with a lifetime of ~50 ns (Fig. 11). However, the lifetime did not change when a stream of argon was passed over the sample (the sunscreen was not bubbled with argon, however), suggesting that oxygen quenching in this environment is inefficient [34]. In addition, singlet oxygen formation was not detected in the sunscreen. Consequently, it is likely that the singlet oxygen quantum yield for TPDC-SA in a commercial sunscreen system will be at least an order of magnitude lower than in neat organic solvents. The triplet state of TPDC-SA is low, at only 47 kcal mo1-1 [35] and therefore will not sensitise triplet state thymine. In contrast, MBC does not show any observable transient absorption on nanosecond timescales and it produces singlet oxygen in low yield (4~A ~ 0.0023) as determined by steady-state irradiation of MBC in deuterated benzene [10].

Figure 11. Triplet state absorption spectra at various times following 355 nm laser excitation of TPDC-SA in Ambre-Solaire SPF 6 sunscreen formulation (1 gl cm -2 loaded onto a 5 • 5 cm quartz plate) [34].

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26.2.5 C i n n a m a t e s

The cinnamates are UVB sunscreens and include 2-ethylhexyl-p-methoxy cinnamate (2-EHMC, tradename Parsol MCX) and 2-ethylhexyl-2-cyano-3,3-diphenyl-2-propanoate (2-EHCDP, also known as Octocrylene). Cinnamates possess high molar absorption coefficients and are heavily used sunscreen ingredients, present in over 90% of sun care products. The spectra of the cis and trans forms of 2-EMHC are given in Fig. 12. Morliere et al. reported the photochemical properties of 2-EHMC in 1982 and showed that the molecule undergoes reversible t r a n s - c i s photoisomerisation [36]. This leads to quite significant changes in the absorption spectrum at ,-310 nm with a considerable loss of absorbance over 10 min of irradiation (using an Osram high-pressure Hg lamp). This observation was also made by Tarrass-Wahlberg et al. in a petroleum jelly solution using 20 MED UVB and 100 mJ cm -2 UVA. However, further irradiation does not cause additional loss, suggesting the isomeric mixture is photostable [28]. 2-EHMC was shown to undergo wavelength-dependent isomerisation with a quantum yield ranging from 0.6 to 1 in both deaerated and aerated solvent systems (ethanol, water, methanol and cyclohexane) [36]. Hill also found similar results, obtaining a value of 0.56 for t~isom(Z_E) and 0.81 for ~bisom(E-Z),using 266 nm LFP [ 10]. Isomerisation occurs within 50 ns and is proposed to occur via the singlet state or a very short-lived triplet state. Furthermore, isomerisation is sensitised via energy transfer, from the triplet state of 5-MOP and 8-MOP [36]. Thus, the triplet state energy level of 2-EHMC is lower than 8-MOP (ET -- 62.6 kcal tool -I) and 5-MOP (ET = 60.5 kcal mo1-1) and therefore should be unable to sensitise triplet state thymine. The exact value of the triplet state energy level was not determined, but the data provide an upper limit. In a later study by Hill et al., the triplet state energy level of 2-EHMC was found to be 57 kcal mo1-1 via high-pressure oxygen perturbation of singlet-triplet absorption bands [37]. There are concerns about the safety of 2-EHMC since it is able to react with itself and form dimers via a [2+2] cycloaddition reaction involving its ethylenic double bond, in a similar manner to thymine, and hence it is possible that 2-EHMC may also form a sunscreen-DNA adduct [14].

Figure 12. Ground state absorption spectra of (i) trans and (ii) cis 2-EHMC in ethanol.

PHOTOCHEMICAL AND PHOTOPHYSICAL PROPERTIES

Figure 13. Absorptionspectrum of 1 •

l0 -4

509

M 2-EHCDP in cyclohexane.

There has been very little research into the photochemistry of 2-EHCDP (see Fig. 13). Mulroy has carried out laser flash photolysis studies but did not detect any triplet state or singlet oxygen production suggesting that either 4~r is zero or the triplet state lifetime is shorter than the detection limits of the instrumentation (~ 10 ns) [11]. However, Allen et al. found the quantum yield of singlet oxygen production to be greater than zero [ 17]. The triplet state energy level has not been reported.

26.2.6 Dibenzoylmethanes The sunscreens that are based on the dibenzoylmethane structure include 4-tert-butyl4'-methoxydibenzoylmethane (BM-DBM) and isopropyl dibenzoylmethane (I-DBM), both of which are UVA sunscreens. BM-DBM is also the most extensively studied UVA sunscreen and much work has been carried out on its parent compound, dibenzoylmethane, DBM. BM-DBM (also known by various tradenames such as Parsol 1789 and Avobenzone) is the most commonly used UVA sunscreen and recent approval by the Food and Drug Administration has extended its use to the USA [38]. I-DBM, however, has been withdrawn from the list of accepted sunscreen ingredients and has not been used since 1994. The advantage of BM-DBM is its high molar absorption coefficient at long UVA wavelengths which is due to the extended chromophore that results from the strong intramolecular hydrogen bonding within the molecule in its chelated enol form (Figs. 2 and 14A). BM-DBM tautomerises from the chelated enol form (the major component in non-UV exposed samples) to a diketo form. The diketo form is observed under steadystate irradiation conditions (Fig. 14B), particularly in solvents such as acetonitrile, and it exhibits an absorption maximum at 260 nm (Fig. 15). The extent of ketonisation is highly dependent on the solvent/emulsion system employed and does not occur to a significant extent in protic solvents such as ethanol. However, quantum yields of diketo production have not been reported.

510

A. CANTRELL ET AL.

Figure

14. Absorption spectrum of BM-DBM in acetonitrile (A) and BM-DBM in a model emulsion preparation following UV irradiation using a 75 W Xe arc lamp (B).

Figure

15. Absorption spectrum of 2

BM-DBM in acetonitrile irradiated using a 75 W xenon arc lamp for 10 min.

• 10 -5 M

Dissipation of absorbed energy is also effected by formation of non-chelated enol (NCE) species (Fig. 16), as first suggested by Veierov et al. in 1977 for DBM [39]. LFP studies reveal the relatively long-lived (millisecond duration but highly solvent dependent) NCE, which may arise via rotation around the single C - C bond or by isomerisation about the C = C double bond producing a Z and E-isomer of the NCE, respectively [40]. There have been numerous subsequent papers on DBM and its derivatives that have attempted to explain the behaviour of DBM and BM-DBM and establish the exact nature of the transient species. The quantum yield of NCE production was determined by Hill as "-~0.25 in various solvents [10]. Both ketonisation and isomerisation have been observed in model emulsion preparations, although the rate of tautomerisation is much slower than in aprotic organic solvents, such as acetonitrile [32]. These processes all involve harmless energy dissipation decay channels, although it must be pointed out that the transient intermediates may possess distinctive photochemical properties. A further advantage of this molecule is that it has a low triplet

PHOTOCHEMICAL AND PHOTOPHYSICAL PROPERTIES

511

MeO

OH

.H~

0 MeOw

~

v

I"

M

e

O

0

~

0 OH MeOf

Figure 16.

Photochemical processes of BM-DBM.

energy level (ET ~ 59 kcal mol -~ [37]) and no triplet state formation or singlet oxygen production has been reported. Many studies on BM-DBM have focused attention on its limited photostability. Roscher et al. [41] showed that BM-DBM undergoes significant photodegradation and several photoproducts were formed (detected by HPLC) that are indicative of carbonyl photochemistry. However, they employed rather severe irradiation conditions (100 h irradiation using wavelengths > 185 nm in cyclohexane). Other workers have also reported photostability problems of BM-DBM [27,28,42-47]. Schwack and Rudolph investigated the photostability of BM-DBM and I-DBM in various solvents (cyclohexane, isooctane, isopropanol and methanol) using UVB and UVA light. They found an 8% degradation for both molecules exposed to UVA and 14% for BM-DBM and 20% for I-DBM following UVB irradiation. Photoproducts were also identified using HPLC and GC-MS and the products found were benzoic acids, benzaldehydes and benzils, all of which indicate the involvement of the diketo form. Furthermore, the sunscreens were found to be stable in isopropanol and methanol where the equilibrium lies almost exclusively towards the enol form [42]. Deflandre and Lang showed BM-DBM (4% weight/weight emulsion sample) to have a 36% loss of absorbance following irradiation using a solar simulator and 320 nm filter, but DBMs containing an ortho hydroxy group were much more stable [27]. Marti-Mestres et al. [43] highlighted the importance of the vehicle into which BMDBM is placed. It was found to be quite stable in isopropyl myristate with only a 12% loss of absorption following 4 h irradiation using a solar simulator. Bonda et al. [44] demonstrated that BM-DBM undergoes loss of absorption following irradiation (735 mJ cm -2) using a 320 nm cut-off filter in cyclohexane, but that addition of a protic hydroxylic solvent only, such as isopropanol, lowers the extent of ketonisation following UVR exposure. Tarrass-Wahlberg et al. also demonstrated the loss of absorbance of

512

A. CANTRELL ET AL.

BM-DBM and the complete loss of absorption in the UVA region after 100 mJ UVA irradiation of I-DBM [28]. The involvement of singlet oxygen and oxy radicals may also be important in the photodegradation of BM-DBM. Dunlap et al. used uric acid as a trap for oxygen species such as 102, OH" and superoxide, O~- produced from various sunscreens following irradiation using solar simulated light. The rate of uric acid oxidation was measured by HPLC. BM-DBM was shown to have the highest rate of uric acid photooxidation of any UVA sunscreen studied including HM-BZP and I-DBM [46]. The UVB sunscreens 2-EHCDP and MBC have been shown to enhance the photostability of BM-DBM [48]. The mechanism of this is not yet understood but may be due to quenching of the triplet state of the diketo form or NCE form, although there is no evidence to suggest that they interact with the NCE directly [32].

26.2.7 Salicylates The salicylates have been in use for some time and include derivatives such as ethylhexyl salicylate, homomenthyl, benzyl and triethanolamine salicylate. The ortho substituted structures are able to form intramolecular hydrogen bonds and exhibit )~max at ~300 nm (non-ortho substituted salicylates have an absorption band at ~--290 nm). Homomenthyl salicylate is reported to undergo cis-trans isomerisation as given in Fig. 17. It was reported that HS exists as 15% cis form and 85% trans form; however, figures of 40% and 60%, respectively, are also reported [7]. Allen et al. (in the same study as for PABA) did not observe any singlet oxygen production from octylsalicylate (2-hydroxybenzoic acid octyl ester) [ 17]. O

II

ht~

CIS

TRANS

Figure 17. Photoisomerisation of homomenthyl salicylate.

26.2.8 Miscellaneous organic sunscreens 2-Phenylbenzimidazole-5-sulphonic acid (PBSA). PBSA, also known, for example, as Parsol HS, is a water-soluble UVB sunscreen approved for use in both Europe and the USA. It has an absorption maximum at 305 nm in ethanol with a molar absorption coefficient of ~26,000 M -1 cm -1 (Fig. 18). There have been very few photochemical studies of this sunscreen, but it has been reported that PBSA is able to sensitise (possibly by electron transfer) the formation of thymine dimers in solutions of the free base [18]. The triplet state energy (determined by Mulroy as 66 kcal mo1-1 from phosphorescence measurements [11 ]) discounts an energy transfer mechanism.

PHOTOCHEMICAL AND PHOTOPHYSICAL PROPERTIES

513

Figure 18. Absorptionspectrum of 2-phenylbenzimidazole-5-sulphonicacid (3.5 x 10-5 M) in ethanol. 26.3 Inorganic systems 26.3.1 Titanium dioxide and zinc oxide The inorganic sunscreens not only scatter and reflect UV radiation but also absorb it. When titanium dioxide is exposed to UVR, absorption of light occurs and an electron is promoted from the valence band to the conduction band, with concurrent formation of a hole, h +. TiO2 --+ e- + h + The separation of these two levels corresponds to the band gap energy, Ebg (the band gap energy of anatase TiO2 corresponds to a wavelength of 387 nm, rutile is 405 nm and ZnO is 384 nm). Migration of both the electron and the hole to the particle surface is then possible. From there several processes may take place: hole-electron recombination, oxidation of an electron donor by the hole, or reduction of an electron acceptor by the electron. Fig. 19 depicts these reactions. For example, water on the surface may react with the hole to form hydroxyl radicals, OH" which are highly reactive species [49,50] and the electron may react with oxygen

Figure 19. Representationof the photoreactions of titanium dioxide.

514

A. CANTRELL ET AL.

to produce the superoxide radical and then go on to form hydrogen peroxide via disproportionation. H20 + h + --+ OH" 4- H + 0 2 -+- e- --+ 02- ~ --+ --+ H202

For a long time inorganic sunscreens were considered undesirable because of their high refractive indices and ability to scatter visible light, which cause 'whitening' of the skin when applied. However, the development of processes for production of ultra-fine particles has overcome this concern since ultra-fine TiO2 is visibly transparent. However, the small particle size may present new problems because of the increase in surface area. Many reports on TiO2 have recounted its photocatalytic capabilities, ability to catalyse the degradation of a variety of organic molecules and form reactive hydroxyl radicals from water adsorbed on the particle surface [49-53]. Thus an increase in surface area, as occurs with ultra-fine particles, may potentially augment the photoactivity of TiO2. The photoactivity of inorganic systems has relevance to the overall potential toxicity of sunscreens, photosensitisation reactions and accelerated photodegradation of organic sunscreens [55-57]. However, inorganic sunscreens are often coated with inert substances such as alumina or octylsilane, which inhibit reaction of adsorbed species with the electron or hole [57]. There have been relatively few studies on the photoactivity of coated TiO2 or ZnO used in sunscreen formulations and indeed, information for consumers on the nature of the metal oxide crystal structure (anatase is much more photoactive than rutile TiO2) and the coatings within sunscreen products is virtually non-existent. Swartz et al. studied the photoactivity of treated and untreated TiO2 samples by electron paramagnetic resonance techniques to monitor OH" formation. They showed that surface treatment with silicone had a significant effect on the relative amounts of spin-trapped hydroxyl radicals from TiO2 and were likely to be less active than uncoated samples [54]. However, Sayre and Dowdy found that some samples of titanium dioxide and zinc oxide used in cosmetic products (to which various coatings have been applied), showed photoactive behaviour towards corn oil that contains unsaturated lipids, including linoleic acid, and therefore could potentially attack skin cell lipids in vivo [58]. Current methods of photoactivity testing of titanium dioxide rely on either the photooxidation of isopropanol or photogreying. Photogreying arises because of formation of coloured Ti 3+, formed by trapping electrons at Ti(IV) sites. This method has disadvantages in that results are often not reproducible and photogreying measures the trapping of electrons by TiO2 rather than photoactivity (i.e. the potential to induce transformations in other substances). However, an alternative testing method for coated titanium dioxide is being developed in our laboratory that involves photoinduced reduction of the stable 1,1-diphenyl-2-picrylhydrazyl radical, DPPH" resulting in a colour change (from purple to yellow) [59]. The mechanism of photocatalysed reduction of DPPH" by TiO2 is not fully understood but an advantage of using DPPH is that it can be employed for dispersions. More research is required on photoactivity testing of titanium dioxide and zinc oxide used in commercial sunscreen products.

0

>. Table 2. Photochemical and photophysical properties of UVA and UVB sunscreens Sunscreen

Major mode of action

MBC (UVB) TPDC-SA (UVA) BM-DBM (UVA)

trans-cis isomerisation trans-cis isomerisation

HMBZP (UVA) PABA (UVB) MA (UVA) 2-EHMC (UVB) OD-PABA (UVB) 2-EHCDP

enol-keto tautomerisation NCE production tautomerisation ISC fluorescence trans-cis isomerisation ISC

~bprocess 0.13-0.3 [311 0.24 [10]

q~T

4~A

ET/kcal mo1-1

rT

~ 0 [101 >0.1 [34] ~,0 [10]

0.0023 [101 ~0.09" [34] ,~0 [10]

55 [101 47 [35] 59 [10]

4.5 its [101 50-120 ns [34] 380 ns [10]

-

~0.6 [9] 0.81 [10]

>. :Z

-

"~0 [16]

~ 0 [10]

0.1 [10]

0.1

-

~0

[11]

-

>0

[11]

0.0029 [10] 0.09-0.12 [9] 0.0012 (trans) [10] 0.0014 (cis) [10] 0.018 [10] ~0[11]

-

75 69 57 58 69

ZZ O ZZ

-

[37] [9]

(trans) [10] (cis) [10] [10]

-

26-200 txs [9] 40 ns [10] 5 p~s <10 ns [ 1 1 ]

t" O

>01161 PBSA

>0

[11]

66

[11]

0.16 ms

[11]

* -- sensitive to [O2], singlet oxygen yields from references [10] and [16] were measured using steady-state irradiation (at 365 nm of Hg arc lamp in deuterated benzene [10]), those from [9] and [34] were measured using time resolved luminescence spectroscopy.

t'r3

516

A. CANTRELL ET AL.

26.4 Summary The modes of energy dissipation of many (organic) sunscreens is via harmless processes. This involves either photoisomerisation or phototautomerisation, and usually proceeds with a high quantum yield. However, often this is less than unity and other processes also take place. These may include fluorescence and triplet state formation, both of which are not desirable (the former since it indicates a significant singlet state lifetime). Table 2 summarises the photochemical and photophysical properties of the sunscreens discussed. Furthermore, the undesirable aspects of sunscreens include the ability to form radicals, DNA-adducts, sensitise the formation of thymine dimers and singlet oxygen. All of these attributes are potentially deleterious to human health and are of concern if there is a possibility for sunscreens to penetrate the skin and interact with biological substrates such as cell lipids or DNA. It is important to minimise the risk of producing reactive excited state or non-excited state species within sunscreen formulations. The possibilities available to manufacturers include producing new sunscreen ingredients that possess ideal photophysical characteristics such as low lying triplet state energies, sunscreens that act as efficient excited state quenchers (of singlet oxygen for example) or as photostabilisers. For example, OD-PABA, MBC and 2-EHMC are able to quench tryptophan triplet state with kq of the order of 1 0 9 - 1 0 l0 M -1 s -1 [11]. The photoactivity of TiOz/ZnO should be tested prior to use in commercial products using a suitable protocol. However, new protocols for testing photoactivity of inorganic sunscreens are required.

A cknowledgements The authors would like to thank Dr. E.J. Land for useful discussions and Photochemistry and Photobiology for permission to reproduce Fig. 5.

References 1 2 3 4 5 6 7 8

G.J. Fisher, S.C. Datta, S.H. Talwar, Z.Q. Wang, J. Varani, S. Kang, J. Voorhees (1996). Molecular basis of sun-induced premature skin aging and retinoid antagonism. Nature, 379, 335-339. M.L. Kripke, A. Jeevan (1993). Immunological effects of UVB radiation. In: A. Shima (Ed), Frontiers of Photobiology. Elsevier, Amsterdam, pp. 537-539. E Urbach (1993). Photocarcinogenesis: Past, present and future. In: A. Shima (Ed), Frontiers of Photobiology. Elsevier, Amsterdam, pp. 403-413. A.R. Young (1997). Chromophores in human skin. Phys. Med. Biol., 42, 789-802. EP. Gasparro, M. Mitchnick, J.E Nash (1998). A review of sunscreen safety and efficacy. Photochem. Photobiol., 68, 243-256. A.A. Lamola (1968). Excited state precursors of thymine photodimers. Photochem. Photobiol., 7, 619-632. N.A. Shaath, N.J. Lowe (1990). Sunscreens. Development, Evaluation and Regulatory Aspects. Marcel Dekker, New York. K. Klein (1992). Encyclopaedia of UV absorbers for sunscreen products. Cosmet. Toiletries, 107, 45-65.

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