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Photodecomposition of several compounds commonly used as sunscreen agents
I. Photoc~in.
Photobiol. A: Chem., 80 (1994) 417-421
Photodecomposition sunscreen agents Nina Jiang
Matheny
Department
Roscher
417
of several compounds
‘, Martin
K.O.
Lindemann,
commonly used as
Suk Bin
Kong,
Cheon
G. Cho
and
Ping
of ChemiFtry, The American Uniwrsity, Washington, DC, 2OOI6-8014 (USA)
Abstract The photolysis reactions of three compounds commonly used as sunscreen agents, Parsol 1789 (1-[4-(1,1dimethylethyl)phenyl]-3-(4-methoxyphenyl)-1,3-propanedione), Oxybenzone ((2-hydroxy-4-methoxyphenyl)phenylmethanone) and Padimate 0 (Zethylhexyl-&(dimethylaminojbenzoate), were investigated to provide a chemical background to aid in the understanding of the photosensitization of the sunscreen agents. Photolysis was carried out in cyclohexane for 70-140 h using a mercury vapor lamp (450 W) without excluding oxygen. Irradiation of Pars.01 1789 in cyclohexane yielded iert-butylbenzene,p-tert-butylbenzoic acid andp-methoxybenzoic acid, products obtained from the combination of the sunscreen with the solvent included the cyclohexyl esters ofp-methoxybenzoic acid,p-teri-butylbenzoic acid and methanoic acid; products obtained from the solvent included cyclohexanol, cyclohexanone and dicyclohexy1 ether. Irradiation of Oxybenzone in cyclohexane for 100 h produced no detectable products by either gas or liquid chromatographic analysis. Oxybenzone was recovered unchanged and no products. were observed from the photoinitiated reaction of oxygen with the solvent. Irradiation of Padimate 0 in cyclohexane yielded the ethylhexyl esters of p-aminobenzoic acid, p-mouomethylaminobenzoic acid and p-dimethylamino(o/m)-methylbenzoic acid, as well as products from the photoinitiated reaction of oxygen with the solvent.
1. Introduction There is a growing interest in cosmetic products containing sunscreen agents. The products are widely available and are used to protect the skin against sunburn. Sunscreen agents prevent the degradation of the cosmetic products by sunlight. However, the regular application of these products may cause irritation and allergic or photoallergic contact dermatitis [1, 21. Studies have shown that a sunscreen agent, a preservative and a non-ionic detergent in an aqueous vehicle will leave an effective amount of sunscreen on the skin even after rinsing [3]. The photostability and photodegradation of sunscreen agents have been studied by many workers by monitoring the spectral changes over time, e.g. the shift in the UV maxima [4] or the irreversible disappearance of the chromophore [5]. The products of photodegradation have not been investigated.
‘Author
to whom correspondence
lOlO-6030/94/$07.00 Q 1994 Else-&r SSDI 1010-6030(94)01043-F
should be addressed.
Sequoia.
AU rights reserved
In this work, the photodecomposition reactions of three compounds commonly used as commercial sunscreen agents were studied in cyclohexane: Parsol 1789 (l-[4-(l,l-dimethylethyl)phenyl]-3(4-methoxyphenyl)-1,3-propanedione) (I) [6], Oxybenzone ((2-hydroxy-4-methoxyphenyl)phenylmethanone) (II) [6] and Padlmate 0 (Zethylhexyl4-(dimethylamino)benate (III} [7].
2. Materials
and methods
2.1. Irradiation [8] Photolysis was performed with a photochemical reaction assembly and mercury vapor immersion lamp (medium pressure, quartz) purchased from Ace Glass Inc. During photolysis, the system was cooled with water to avoid any possible thermal reactions caused by the emitted heat from the lamp. The quartz filtered some of the short-wavelength rays of the lamp, but transmitted the wavelengths 185-4000 nm. No effort was made to exclude oxygen from the reaction system during photolysis.
418
N.M. Roscher
et al. I Photodecomposition
2.2. ChemicaZs Parsol 1789, Oxybenzone and Padimate 0 were supplied by Johnson & Johnson Co. and were used without further purification. The chemicals were of the highest grade available and included cyclohexane, cyclohexene, cyclohexanone and rer?butylbenzene (J.T. Baker Chemical Company), p-methoxybenzoic acid, p-tert-butylbenzoic acid, p-methoxyacetophenone, methoxybenzene, pmethylmethoxybenzcne and p-methoxybenzaldehyde (Aldrich Chemical Company),p-dimethylaminobenzoic acid (Kodak Chemical Company) and cyclohexanol, cyclohexanone and methanoic acid (Fisher Scientific Products Co.). 2.3. Chromatography A Hewlett Packard 5890 gas chromatograph, equipped with a polydimethylsiloxane capillary column (RSL-150; 10 m; inside diameter, 0.53 mm) (Alltech Associates), was used for the separation of the reaction products from Parsol 1789, Padimate 0 and Oxybenzone. High pressure liquid chromatographic (HPLC) analysis of Padimate 0 was performed on a Hewlett Packard 1090 with an RP-18-DB column. 2.4. Spectroscofl Mass spectra were measured on a Hewlett Packard 5995 gas chromatograph/mass spectrometer (GC/MS) (electron impact (EI), 70 eV). A polydimethylsiloxane capillary column (RSLlSO; 15 m; inside diameter, 0.35 m) was used. Any values for mass spectra (m/e) less than 5% were not reported. Nuclear magnetic resonance (NMR) spectra were measured on a Varian XL-300 using tetramethylsilane (T&IS) as internal standard. I-IV-visible spectra were measured on a Hewlett Packard 8452A diode array spectrophotometer. IR spectra were obtained using a Perkin-Elmer 397 spectrophotometer. 2.5. Pars01 1789 Parsol 1789 (0.01 M) in cyclohexane was irradiated for 100 h. Thin layer chromatography of the products using chloroform as eluent indicated nine products with no recovered starting material. By column chromatography and recrystallization, p-methoxybenzoic acid was isolated and was compared with a known sample. The majority of the products were identified by comparison with known samples by considering identical thin layer and gas chromatography retention times and by matching the GUMS data. The dicyclohexyl ether was identified by matching its mass spectrum with the Wiley computerized mass spectral data base [9].
of compoundsused
as sunscreen
agents
2.6. Cycloheranc Cyclohexane was irradiated for 140 h under the same conditions as used for the sunscreen compounds. No decomposition of the solution was observed. 2.7. Oxybenzone A cyclohexane solution of Oxybenzone (0.01 M) was irradiated for 100 h with stirring (magnetic). After this time, the solution was concentrated and analyzed by the GC and GUMS. The starting material was totally recovered with no evidence of traces of any other materials. 2.8. Pudimate 0 Padimate 0 (0.01 M) in cyclohexane was irradiated for 70, 100 and 140 h with stirring (magnetic). After irradiation the solution was concentrated and analyzed by the GC, GUMS and liquid chromatograph (LC). In addition to the starting material, three products were identified from the sunscreen compound. The monomethylamine derivative and the unsubstituted amine derivative were readily identified by comparison with authentic samples. p-Dimethylaminomethylbenzoic acid is a new compound not reported previously. Mass spectra m/z (percentage base peak): 41.1 (58), 42.1 (41), 43.1 (41), 51.0 (18), 55.0 (43), 56.1 (30), 57.1 (35), 65.0 (30), 69.1 (22), 70.1 (42), 71.1 (18), 76.0 (15), 77.0 (34), 78.1 (21), 79.0 (26) 83.1 (27) 844.1 (19) 104.1 (19) 105.1 (17), 106.1 {23), 112.1 (25), 121.0 (67), 122.1 (19), 132.0 (20), 134.1 (34), 135.1 (19), 138.1 (40), 141.1 (27), 150.1 (34), 151.1 (41), 162.1 (59), 163.1 (20), 179.1 (loo), 180.1 (49), 181.1 (49), 291.1 (17).
3. Results and discussion The compounds Parsol 1789, Oxybenzone and Padimate 0 were irradiated with a medium pressure mercury vapor immersion lamp in a quartz reaction vessel for 70-140 h as solutions in cyclohexane [6,7]. This lamp allowed a large amount of sample to be irradiated in an efficient way. The quartz immersion well was water cooled to prevent thermal reactions. The solutions were stirred magnetically to provide continual mixing, with no effort made to exclude oxygen, since oxygen would be present in any topical application of sunscreen agents. 3.1. Pars01 1789 (I) A solution of Parsol 1789 in cyclohexane was irradiated for 100 h under the conditions described
NM. Roscher et aL I Photodecomposition of compunds
above; total decomposition of Parsol 1789 was observed, as well as several products arising from the photoinitiated decomposition of the solvent (Fig. 1). Products identified from Parsol 1789 included tert-butylbeuzene, p-methoxybenzoic acid and p-tert-butylbenzoic acid. p-tert-Butylbenzoic acid predominates in all cases by gas chromatographic analysis. Generally, the amount of p-tertbutylbenzoic acid obtained was two to three times the p-methoxybenzoic acid yield with about 10%-U% tert-butylbenzene. Two of the products, the cyclohexyl esters of p-methoxybenzoic acid andp-tert-butylbenzoic acid, originated from the reaction of the solvent with the radicals formed on decomposition of Parsol 1789. In a typical run, each of the cyclohexyl esters represented less than 5% of the products from Parsol 1789. Qclohexane yielded cyclohexanol, cyclohexanone and dicyclohexyl ether from the photoinitiated reaction with oxygen. The cyclohexyl ester of methanoic acid was also observed in the GU MS and presumably arises from the interaction of the solvent with the photodecomposition product of the sunscreen. The total amount of products from cyclohexane varied. In all cases cyclohexanol was the main product. In one run the relative amounts by gas chromatography were cyclohexanol (37%), cyclohexanone (24%), dicyclohexyl ether (9%), cyclohexyl ester of methanoic acid (27%) and cyclohexyl esters of p-methoxybenzoic acid and p-tert-butylbenzoic acid (2%) with twice as much of the ester of p-tert-butylbenzoic acid. Although tert-butylbenzene was observed, no methoxybenzene was detectable by gas chroma-
used as sunscreen agents
tography using a spiked sample technique. Another research group [lo] has reported the observation of p-methoxybenzaldehyde, but we did not obtain this material under our reaction conditions. It is assumed that the long reaction time would have caused the oxidation of any p-methoxybenzaldehyde into p-methoxybenzoic acid. No p-methoxyacetophenone or p-tert-butylacetophenone was detected. Although single fragment molecules would also have been present in the solution, such as methanol, carbon monoxide and methanoic acid, no attempt was made to detect these. However, the observation of the cyclohexyl ester of methanoic acid as a minor product in the solution indicates their existence. A possible mechanism for the formation of the products from Parsol 1789 is presented in Fig. 2 [H-14]. p-Methoxybenzoic acid and p-tert-butylbenzoic acid should be formed by the same mechanistic route: type I cleavage and reaction with oxygen dissolved in the solvent [15]. The radicals formed from Parsol 1789 and oxygen abstract hydrogen mainly from the solvent (cyclohexane). The cyclohexyl radical can react with oxygen leading to cyclohexanol, cyclohexanone and dicyclohexyl ether. The cyclohexyl radical can also react
R=H,C6HII
wsc~ + Q-OH +
+
o=
O-OH
0
o-0-L +(-J-o-(-J
Fig. 1. Decomposition
of Parsol
1789 (I).
419
Fig. 2. Proposed 1789.
mechanism
for the decomposition
of Parsol
420
NM.
Rascher et al. f Phofodecomposition
with the other radicals from Parsol to the cyclohexyl esters observed.
1789 leading
3.2. Oxybenwne (II) A solution of Oxybenzone (Fig. 3) in cyclohexane irradiated for 100 h was stable with no detectable products by either gas or liquid chromatographic analysis. The Oxybenzone was recovered unchanged and no products were observed from the photoinitiated reaction of oxygen with the solvent. This stability supports the clinical studies which show that Oxybenzone is safe for topical application to humans [16], Recently, Van Haver d al. [17] have reported that, during laser-induced optoacoustic spectroscopy, the parent compound of Oxybenzone, 2_hydroxybenzophenone, is photostable at low laser pulse energies. 3.3. Padimate 0 (III) After 70 h of irradiation of Padimate 0 in cyclohexane, the monomethylaminobenzoic acid cyclohexyl ester was observed with no additional products detectable. However, after 140 h of irradiation, the p-monomethylaminobenoic acid ethylhexyl ester (21%) was observed together with p-dimethylamino-(o/m)-methylbenzoic acid ethylhexyl ester (5%) and less than 1% of the paminobenzoic acid ethylhexyl ester (Fig. 4), with the balance recovered starting material. Control studies showed that none of the materials were present as contaminants in the original material. In addition, products from the photoinitiated reaction of oxygen with the solvent were observed,
of compoundsused as sumcreenagents
including cyctohexanol. Under these conditions, therewas no evidence of the azo derivative obtained by Gasparro [18] and formed from the parent acid, p-aminobenzoic acid. For the p-dimethylamino-(o/m)-methylbenzoic acid ethylhexyl ester, we have been unable to determine unequivocally whether the methyl is in the ortho or meta position. Mass spectral and proton NMR analysis indicate clearly that the additional methyl group is on the aromatic ring. Mass spectral analysis indicates that the molecular weight is 291. The proton NMR spectrum is similar to that of the starting material with an additional peak at 2.1 (TMS =O). Neither the o- nor m-methyl derivative has been reported previously. The parent o-methyl-p-dimethylaminobenzoic acid was prepared by McAlees et al. [19], but complete spectral data were not provided. Consideration of the spectral data of similarly substituted molecules does not provide a definitive answer. In our studies, the free radical methyl addition over time is important to understand the breakdown of the sunscreen compound. 3.4. p-Dimethylarninobenzoic acid p-Dimethylaminobenzoic acidwas also irradiated in aqueous solution to determine if a similar breakdown occurred or if any of the products reported for the photoexcitation ofp-aminobenzoic acid were observed 1181. No breakdown of pdimethylaminobenzoic acid was detected under the conditions used in our study. 4. Conclusions These studies of the photodegradation of sunscreen compounds were carried out in an organic solvent to obtain unequivocal rest&s. Formulation on the skin is a more complex system. However, the photodecomposition products obtained suggest that careful consideration should be given to the long-term use of several of these materials as sunscreen agents.
II
Fig. 3. Oxybenzone
(II).
Acknowledgment CHJ\ a3
CH I
/N
3
II
-Q
I ’ -C--R CH3
F-‘H2
R = -CH2 dH CH2 CHZCH2 CH 3
+ 0 II
C-OR Fig. 4. Decomposition
The support of Johnson & Johnson Consumer Products Co., Inc. is gratefully acknowledged.
of Padimate 0 (III).
References 1 S. Schauder and H. Ippen, Photodetmatologv, 3 (1986) 140. 2 J.S.C. English, J.R. White and E. Cronin, Canfact Demo., 17 (1987) 159.
N.M. Roscher et al. I Photodecomposition 3 J.E. Bernstein, (I..!? Parent 4,701,321; Chem. Abstr., 108 (1988) 818139d. 4 H. Flmdt-Hansen, C.J. Nielsen and P. Thune, Photodennoto&y, 5 (1988) 257. 5 A. DeFIandre and G. Lang, Int 1. Cos. Sci, 10 (1988) 53. 6 C.G. Cho, M.S. Thesis, The American University, Washington DC, 1989. 7 P. Bang, MS. Thesis, The American University, Washington DC, 1990. 8 F. Urbach, Photodermatologv, 6 (1989) 177. 9 F.W. McIafferty and D.B. Stouffer (eds.), J.W. Wiley/NBS Mass Spectral Data, Vol. 1, National Bureau of Standards, 1989. 10 M.K.G. Lindemann, Johnson &Johnson Consumer Products Co, Inc., personal communicalion, 1989.
of compounds used os sunscreen agents
421
11 P. Yankov and S. Saltiel, C/rem. Phys. L&t., 128 (1986) 517. 12 J.C. Scaiano, E.B. Abuin and L.C. Stewart, 1 Am. Chem. sot., 104 (1982) 5673. 13 R.W. Redmund, J.C. Scaiano and L.J. Johnston,J. Am. Chem. sot., 112 (1990) 398. 14 J.C. Gramain and R. Remuson, L Org. Chem., 50 (1985) 1120. 15 D.S. Weiss, Org. Phorochem., 5 (1981) 347. 16 R.C. Elder, X Am. Coil. Toxicoi., Z(5) (1983) 40. 17 P. Van Haver, L. Viaene, M. Van der Auweraer and F.C. De Schryver, .I. Photo&em. Photobioi., A: Chem., 63(2) (1992) 265. 18 F.P. Gasparro, Photodermatology, 2 (1985) 151. 19 A-l. M&lees, R. McCrcadle and D.W. Snedden, 1. Chem. Sot., Perkin Trans. I, (1977) 2030.
Photobiol. A: Chem., 80 (1994) 417-421
Photodecomposition sunscreen agents Nina Jiang
Matheny
Department
Roscher
417
of several compounds
‘, Martin
K.O.
Lindemann,
commonly used as
Suk Bin
Kong,
Cheon
G. Cho
and
Ping
of ChemiFtry, The American Uniwrsity, Washington, DC, 2OOI6-8014 (USA)
Abstract The photolysis reactions of three compounds commonly used as sunscreen agents, Parsol 1789 (1-[4-(1,1dimethylethyl)phenyl]-3-(4-methoxyphenyl)-1,3-propanedione), Oxybenzone ((2-hydroxy-4-methoxyphenyl)phenylmethanone) and Padimate 0 (Zethylhexyl-&(dimethylaminojbenzoate), were investigated to provide a chemical background to aid in the understanding of the photosensitization of the sunscreen agents. Photolysis was carried out in cyclohexane for 70-140 h using a mercury vapor lamp (450 W) without excluding oxygen. Irradiation of Pars.01 1789 in cyclohexane yielded iert-butylbenzene,p-tert-butylbenzoic acid andp-methoxybenzoic acid, products obtained from the combination of the sunscreen with the solvent included the cyclohexyl esters ofp-methoxybenzoic acid,p-teri-butylbenzoic acid and methanoic acid; products obtained from the solvent included cyclohexanol, cyclohexanone and dicyclohexy1 ether. Irradiation of Oxybenzone in cyclohexane for 100 h produced no detectable products by either gas or liquid chromatographic analysis. Oxybenzone was recovered unchanged and no products. were observed from the photoinitiated reaction of oxygen with the solvent. Irradiation of Padimate 0 in cyclohexane yielded the ethylhexyl esters of p-aminobenzoic acid, p-mouomethylaminobenzoic acid and p-dimethylamino(o/m)-methylbenzoic acid, as well as products from the photoinitiated reaction of oxygen with the solvent.
1. Introduction There is a growing interest in cosmetic products containing sunscreen agents. The products are widely available and are used to protect the skin against sunburn. Sunscreen agents prevent the degradation of the cosmetic products by sunlight. However, the regular application of these products may cause irritation and allergic or photoallergic contact dermatitis [1, 21. Studies have shown that a sunscreen agent, a preservative and a non-ionic detergent in an aqueous vehicle will leave an effective amount of sunscreen on the skin even after rinsing [3]. The photostability and photodegradation of sunscreen agents have been studied by many workers by monitoring the spectral changes over time, e.g. the shift in the UV maxima [4] or the irreversible disappearance of the chromophore [5]. The products of photodegradation have not been investigated.
‘Author
to whom correspondence
lOlO-6030/94/$07.00 Q 1994 Else-&r SSDI 1010-6030(94)01043-F
should be addressed.
Sequoia.
AU rights reserved
In this work, the photodecomposition reactions of three compounds commonly used as commercial sunscreen agents were studied in cyclohexane: Parsol 1789 (l-[4-(l,l-dimethylethyl)phenyl]-3(4-methoxyphenyl)-1,3-propanedione) (I) [6], Oxybenzone ((2-hydroxy-4-methoxyphenyl)phenylmethanone) (II) [6] and Padlmate 0 (Zethylhexyl4-(dimethylamino)benate (III} [7].
2. Materials
and methods
2.1. Irradiation [8] Photolysis was performed with a photochemical reaction assembly and mercury vapor immersion lamp (medium pressure, quartz) purchased from Ace Glass Inc. During photolysis, the system was cooled with water to avoid any possible thermal reactions caused by the emitted heat from the lamp. The quartz filtered some of the short-wavelength rays of the lamp, but transmitted the wavelengths 185-4000 nm. No effort was made to exclude oxygen from the reaction system during photolysis.
418
N.M. Roscher
et al. I Photodecomposition
2.2. ChemicaZs Parsol 1789, Oxybenzone and Padimate 0 were supplied by Johnson & Johnson Co. and were used without further purification. The chemicals were of the highest grade available and included cyclohexane, cyclohexene, cyclohexanone and rer?butylbenzene (J.T. Baker Chemical Company), p-methoxybenzoic acid, p-tert-butylbenzoic acid, p-methoxyacetophenone, methoxybenzene, pmethylmethoxybenzcne and p-methoxybenzaldehyde (Aldrich Chemical Company),p-dimethylaminobenzoic acid (Kodak Chemical Company) and cyclohexanol, cyclohexanone and methanoic acid (Fisher Scientific Products Co.). 2.3. Chromatography A Hewlett Packard 5890 gas chromatograph, equipped with a polydimethylsiloxane capillary column (RSL-150; 10 m; inside diameter, 0.53 mm) (Alltech Associates), was used for the separation of the reaction products from Parsol 1789, Padimate 0 and Oxybenzone. High pressure liquid chromatographic (HPLC) analysis of Padimate 0 was performed on a Hewlett Packard 1090 with an RP-18-DB column. 2.4. Spectroscofl Mass spectra were measured on a Hewlett Packard 5995 gas chromatograph/mass spectrometer (GC/MS) (electron impact (EI), 70 eV). A polydimethylsiloxane capillary column (RSLlSO; 15 m; inside diameter, 0.35 m) was used. Any values for mass spectra (m/e) less than 5% were not reported. Nuclear magnetic resonance (NMR) spectra were measured on a Varian XL-300 using tetramethylsilane (T&IS) as internal standard. I-IV-visible spectra were measured on a Hewlett Packard 8452A diode array spectrophotometer. IR spectra were obtained using a Perkin-Elmer 397 spectrophotometer. 2.5. Pars01 1789 Parsol 1789 (0.01 M) in cyclohexane was irradiated for 100 h. Thin layer chromatography of the products using chloroform as eluent indicated nine products with no recovered starting material. By column chromatography and recrystallization, p-methoxybenzoic acid was isolated and was compared with a known sample. The majority of the products were identified by comparison with known samples by considering identical thin layer and gas chromatography retention times and by matching the GUMS data. The dicyclohexyl ether was identified by matching its mass spectrum with the Wiley computerized mass spectral data base [9].
of compoundsused
as sunscreen
agents
2.6. Cycloheranc Cyclohexane was irradiated for 140 h under the same conditions as used for the sunscreen compounds. No decomposition of the solution was observed. 2.7. Oxybenzone A cyclohexane solution of Oxybenzone (0.01 M) was irradiated for 100 h with stirring (magnetic). After this time, the solution was concentrated and analyzed by the GC and GUMS. The starting material was totally recovered with no evidence of traces of any other materials. 2.8. Pudimate 0 Padimate 0 (0.01 M) in cyclohexane was irradiated for 70, 100 and 140 h with stirring (magnetic). After irradiation the solution was concentrated and analyzed by the GC, GUMS and liquid chromatograph (LC). In addition to the starting material, three products were identified from the sunscreen compound. The monomethylamine derivative and the unsubstituted amine derivative were readily identified by comparison with authentic samples. p-Dimethylaminomethylbenzoic acid is a new compound not reported previously. Mass spectra m/z (percentage base peak): 41.1 (58), 42.1 (41), 43.1 (41), 51.0 (18), 55.0 (43), 56.1 (30), 57.1 (35), 65.0 (30), 69.1 (22), 70.1 (42), 71.1 (18), 76.0 (15), 77.0 (34), 78.1 (21), 79.0 (26) 83.1 (27) 844.1 (19) 104.1 (19) 105.1 (17), 106.1 {23), 112.1 (25), 121.0 (67), 122.1 (19), 132.0 (20), 134.1 (34), 135.1 (19), 138.1 (40), 141.1 (27), 150.1 (34), 151.1 (41), 162.1 (59), 163.1 (20), 179.1 (loo), 180.1 (49), 181.1 (49), 291.1 (17).
3. Results and discussion The compounds Parsol 1789, Oxybenzone and Padimate 0 were irradiated with a medium pressure mercury vapor immersion lamp in a quartz reaction vessel for 70-140 h as solutions in cyclohexane [6,7]. This lamp allowed a large amount of sample to be irradiated in an efficient way. The quartz immersion well was water cooled to prevent thermal reactions. The solutions were stirred magnetically to provide continual mixing, with no effort made to exclude oxygen, since oxygen would be present in any topical application of sunscreen agents. 3.1. Pars01 1789 (I) A solution of Parsol 1789 in cyclohexane was irradiated for 100 h under the conditions described
NM. Roscher et aL I Photodecomposition of compunds
above; total decomposition of Parsol 1789 was observed, as well as several products arising from the photoinitiated decomposition of the solvent (Fig. 1). Products identified from Parsol 1789 included tert-butylbeuzene, p-methoxybenzoic acid and p-tert-butylbenzoic acid. p-tert-Butylbenzoic acid predominates in all cases by gas chromatographic analysis. Generally, the amount of p-tertbutylbenzoic acid obtained was two to three times the p-methoxybenzoic acid yield with about 10%-U% tert-butylbenzene. Two of the products, the cyclohexyl esters of p-methoxybenzoic acid andp-tert-butylbenzoic acid, originated from the reaction of the solvent with the radicals formed on decomposition of Parsol 1789. In a typical run, each of the cyclohexyl esters represented less than 5% of the products from Parsol 1789. Qclohexane yielded cyclohexanol, cyclohexanone and dicyclohexyl ether from the photoinitiated reaction with oxygen. The cyclohexyl ester of methanoic acid was also observed in the GU MS and presumably arises from the interaction of the solvent with the photodecomposition product of the sunscreen. The total amount of products from cyclohexane varied. In all cases cyclohexanol was the main product. In one run the relative amounts by gas chromatography were cyclohexanol (37%), cyclohexanone (24%), dicyclohexyl ether (9%), cyclohexyl ester of methanoic acid (27%) and cyclohexyl esters of p-methoxybenzoic acid and p-tert-butylbenzoic acid (2%) with twice as much of the ester of p-tert-butylbenzoic acid. Although tert-butylbenzene was observed, no methoxybenzene was detectable by gas chroma-
used as sunscreen agents
tography using a spiked sample technique. Another research group [lo] has reported the observation of p-methoxybenzaldehyde, but we did not obtain this material under our reaction conditions. It is assumed that the long reaction time would have caused the oxidation of any p-methoxybenzaldehyde into p-methoxybenzoic acid. No p-methoxyacetophenone or p-tert-butylacetophenone was detected. Although single fragment molecules would also have been present in the solution, such as methanol, carbon monoxide and methanoic acid, no attempt was made to detect these. However, the observation of the cyclohexyl ester of methanoic acid as a minor product in the solution indicates their existence. A possible mechanism for the formation of the products from Parsol 1789 is presented in Fig. 2 [H-14]. p-Methoxybenzoic acid and p-tert-butylbenzoic acid should be formed by the same mechanistic route: type I cleavage and reaction with oxygen dissolved in the solvent [15]. The radicals formed from Parsol 1789 and oxygen abstract hydrogen mainly from the solvent (cyclohexane). The cyclohexyl radical can react with oxygen leading to cyclohexanol, cyclohexanone and dicyclohexyl ether. The cyclohexyl radical can also react
R=H,C6HII
wsc~ + Q-OH +
+
o=
O-OH
0
o-0-L +(-J-o-(-J
Fig. 1. Decomposition
of Parsol
1789 (I).
419
Fig. 2. Proposed 1789.
mechanism
for the decomposition
of Parsol
420
NM.
Rascher et al. f Phofodecomposition
with the other radicals from Parsol to the cyclohexyl esters observed.
1789 leading
3.2. Oxybenwne (II) A solution of Oxybenzone (Fig. 3) in cyclohexane irradiated for 100 h was stable with no detectable products by either gas or liquid chromatographic analysis. The Oxybenzone was recovered unchanged and no products were observed from the photoinitiated reaction of oxygen with the solvent. This stability supports the clinical studies which show that Oxybenzone is safe for topical application to humans [16], Recently, Van Haver d al. [17] have reported that, during laser-induced optoacoustic spectroscopy, the parent compound of Oxybenzone, 2_hydroxybenzophenone, is photostable at low laser pulse energies. 3.3. Padimate 0 (III) After 70 h of irradiation of Padimate 0 in cyclohexane, the monomethylaminobenzoic acid cyclohexyl ester was observed with no additional products detectable. However, after 140 h of irradiation, the p-monomethylaminobenoic acid ethylhexyl ester (21%) was observed together with p-dimethylamino-(o/m)-methylbenzoic acid ethylhexyl ester (5%) and less than 1% of the paminobenzoic acid ethylhexyl ester (Fig. 4), with the balance recovered starting material. Control studies showed that none of the materials were present as contaminants in the original material. In addition, products from the photoinitiated reaction of oxygen with the solvent were observed,
of compoundsused as sumcreenagents
including cyctohexanol. Under these conditions, therewas no evidence of the azo derivative obtained by Gasparro [18] and formed from the parent acid, p-aminobenzoic acid. For the p-dimethylamino-(o/m)-methylbenzoic acid ethylhexyl ester, we have been unable to determine unequivocally whether the methyl is in the ortho or meta position. Mass spectral and proton NMR analysis indicate clearly that the additional methyl group is on the aromatic ring. Mass spectral analysis indicates that the molecular weight is 291. The proton NMR spectrum is similar to that of the starting material with an additional peak at 2.1 (TMS =O). Neither the o- nor m-methyl derivative has been reported previously. The parent o-methyl-p-dimethylaminobenzoic acid was prepared by McAlees et al. [19], but complete spectral data were not provided. Consideration of the spectral data of similarly substituted molecules does not provide a definitive answer. In our studies, the free radical methyl addition over time is important to understand the breakdown of the sunscreen compound. 3.4. p-Dimethylarninobenzoic acid p-Dimethylaminobenzoic acidwas also irradiated in aqueous solution to determine if a similar breakdown occurred or if any of the products reported for the photoexcitation ofp-aminobenzoic acid were observed 1181. No breakdown of pdimethylaminobenzoic acid was detected under the conditions used in our study. 4. Conclusions These studies of the photodegradation of sunscreen compounds were carried out in an organic solvent to obtain unequivocal rest&s. Formulation on the skin is a more complex system. However, the photodecomposition products obtained suggest that careful consideration should be given to the long-term use of several of these materials as sunscreen agents.
II
Fig. 3. Oxybenzone
(II).
Acknowledgment CHJ\ a3
CH I
/N
3
II
-Q
I ’ -C--R CH3
F-‘H2
R = -CH2 dH CH2 CHZCH2 CH 3
+ 0 II
C-OR Fig. 4. Decomposition
The support of Johnson & Johnson Consumer Products Co., Inc. is gratefully acknowledged.
of Padimate 0 (III).
References 1 S. Schauder and H. Ippen, Photodetmatologv, 3 (1986) 140. 2 J.S.C. English, J.R. White and E. Cronin, Canfact Demo., 17 (1987) 159.
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of compounds used os sunscreen agents
421
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