Benchmark studies of UV–vis spectra simulation for cinnamates with UV filter profile

  • Ricardo D’A. Garcia
  • Vinícius G. Maltarollo
  • Káthia M. Honório
  • Gustavo H. G. TrossiniEmail author
Original Paper


Skin cancer is a serious public health problem worldwide, being incident over all five continents and affecting an increasing number of people. As sunscreens are considered an important preventive measure, studies to develop better and safer sunscreens are crucial. Cinnamates are UVB filters with good efficiency and cost-benefit, therefore, their study could lead to the development of new UV filters. A benchmark to define the most suitable density functional theory (DFT) functional to predict UV–vis spectra for ethylhexyl methoxycinnamate was performed. Time-dependent DFT (TD-DFT) calculations were then carried out [B3LYP/6-311 + G(d,p) and B3P86/6-311 + G(d,p) in methanol environment] for seven cinammete derivatives implemented in the Gaussian 03 package. All DFT/TD-DFT simulations were performed after a conformational search with the Monte-Carlo method and MMFF94 force field. B3LYP and B3P86 functionals were better at reproducing closely the experimental spectra of ethylhexyl methoxycinnamate. Calculations of seven cinnamates showed a λmax of around 310 nm, corroborating literature reports. It was observed that the energy for the main electronic transition was around 3.95 eV and could be explained by electron delocalization on the aromatic ring and ester group, which is important to UV absorption. The methodology employed proved to be suitable for determination of the UV spectra of cinnamates and could be used as a tool for the development of novel UV filters.


Cinnamates TD-DFT Molecular modeling UV filters UV spectra simulation 



The authors would like to thank FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for financial support.

Supplementary material

894_2015_2689_MOESM1_ESM.docx (1.8 mb)
ESM 1 (DOCX 1871 kb)


  1. 1.
    Fartasch M, Diepgen TL, Schmitt J, Drexler H (2012) The relationship between accupational Sun exposure and non-melanoma skin cancer—clinical basics, epidemiolog, occupational disease evaluation, and prevention. Dtsch Arztebl Int 109:715–720Google Scholar
  2. 2.
    Ratushny V, Gober MD, Hick R, Ridky TW, Seykora JT (2012) From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma. J Clin Invest 122:454–472CrossRefGoogle Scholar
  3. 3.
    Agbai OM, Buster K, Sanchez M, Hernandez C, Kundu RV, Chiu M, Roberts WE, Draelos ZD, Bhushan R, Taylor SC, Lim HW (2014) Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public. J Am Acad Dermatol 70:748–762CrossRefGoogle Scholar
  4. 4.
    Noomane A, Hbaieb S, Bolzinger M, Briançon S, Chevalier Y, Kalfat R (2014) Effectiveness of grafting modes of methoxycinnamate sunscreen onto sílica particles. Colloid Surf A 441:653–663CrossRefGoogle Scholar
  5. 5.
    Latha MS, Martis J, Shobia V, Sham Shinde R, Bangera S, Krishnankutty B, Bellary S, Varughese S, Rao P, Naveen Kumar BR (2013) Sunscreening agents: a review. J Clin Aesthet Dermatol 6:16–26Google Scholar
  6. 6.
    Hirst NG, Gordon LG, Scuffham PA, Green AC (2012) Lifetime cost-effectiveness of skin cancer prevention through promotion of daily sunscreen use. Value Health 15:261–268CrossRefGoogle Scholar
  7. 7.
    Monteiro MSSB, Ozzetti RA, Vergnanini AL, de Brito-Gitirana L, Volpato NM, de Freitas ZMF, Ricci-Junior E, dos Santos EP (2012) Evaluation of octyl p-methoxycinnamate included in liposomes and cyclodextrins in anti-solar preparations: preparations, characterizations and in vitro penetration studies. Int J Nanomed 7:3045–3058Google Scholar
  8. 8.
    Sambandan DR, Ratner D (2011) Sunscreens: an overview and update. J Am Acad Dermatol 64:748–758CrossRefGoogle Scholar
  9. 9.
    Millot M, Di Meo F, Tomasi S, Boustie J, Trouillas P (2012) Photoprotective capacities of lichen metabolites: a joint theoretical and experimental study. J Photochem Photobiol B 111:17–26CrossRefGoogle Scholar
  10. 10.
    Santos AJM, Miranda MS, da Silva JCGE (2012) The degradation products of UV filters in aqueous and chlorinated aqueous solutions. Water Res 46:3167–3176CrossRefGoogle Scholar
  11. 11.
    Nash JF, Tanner PR (2014) Relevance of UV filter/sunscreen product photostability to human safety. Photodermatol Photo 30:88–95CrossRefGoogle Scholar
  12. 12.
    Leach AR (2001) Molecular modeling: principles and applications, 2nd edn. Prentice Hall, LondonGoogle Scholar
  13. 13.
    Brémond EAG, Kieffer J, Adamo C (2010) A reliable method for fitting TD-DFT transitions to experimental UV-visible spectra. J Mol Struct Theochem 954:52–56CrossRefGoogle Scholar
  14. 14.
    Jacquemin D, Peltier C, Ciofini H (2010) On the absorption spectra of recently synthesized carbonyl dyes: TD-DFT insights. J Phys Chem A 114:9579–9582CrossRefGoogle Scholar
  15. 15.
    Anouar EH, Gierschner J, Duroux J, Trouillas P (2012) UV/Visible spectra of polyphenols: a time-dependent density functional theory study. Food Chem 131:79–89CrossRefGoogle Scholar
  16. 16.
    Corrêa BAM, Gonçalves AS, de Souza AMT, Freitas CA, Cabral LM, Albuquerque MG, Castro HC, dos Santos EP, Rodrigues CR (2012) Molecular modeling studies of the structural, eletronic, and UV absorption properties of benzophenone derivatives. J Phys Chem A 116:10927–10933CrossRefGoogle Scholar
  17. 17.
    Karabacak M, Kurt M, Cinar M, Ayyppan S, Sudha S, Sundaraganesan N (2012) The spectroscopic (FT-IR, FT-Raman, UV) and first order hiperpolarizability, HOMO and LUMO analysis of 3-aminobenzophenone by density functional method. Spectrochim Acta A 92:365–376CrossRefGoogle Scholar
  18. 18.
    Liu L, Gao H (2012) Molecular structure and vibrational spectra of ibuprofen using density function theory calculations. Spectrochim Acta A 89:201–209CrossRefGoogle Scholar
  19. 19.
    Sridevi C, Shanthi G, Velraj G (2012) Structural, vibrational, electronic, NMR and reactivity analyses of 2-amino-4H-chromene-3-carbonitrile (ACC) by ab initio HF and DFT calculations. Spectrochim Acta A 89:46–54CrossRefGoogle Scholar
  20. 20.
    Govindarajan M, Karabacak M, Suvitha A, Periandy S (2012) FT-IR, FT-Raman, ab initio, HF and DFT studies, NBO, HOMO-LUMO and eletronic structure calculations on 4-chloro-3-nitrotoluene. Spectrochim Acta A 89:137–148CrossRefGoogle Scholar
  21. 21.
    Oltean M, Calborean A, Mile G, Vidrighin M, Iosin M, Leopold L, Maniu D, Leopold N, Chis V (2012) Absorption spectra of PTCDI: a combined UV–vis and TD-DFT study. Spectrochim Acta A 97:703–710CrossRefGoogle Scholar
  22. 22.
    Honório KM, da Silva ABF (2003) An AM1 study on the electron-donating and electron-accepting character of biomolecules. Int J Quantum Chem 95:126–132CrossRefGoogle Scholar
  23. 23.
    Arroio A, Honório KM, da Silva ABF (2010) Quantum chemical properties used in structure-activity relationship studies. Quim Nov. 33:694–699Google Scholar
  24. 24.
    Zhang S, Chen J, Qiao X, Ge L, Cai X, Na G (2010) Quantum chemical investigation and experimental verification on the aquatic photochemistry of the sunscreen 2-phenylbenzimidazole-5-sulfonic acid. Environ Sci Technol 44:7484–7490CrossRefGoogle Scholar
  25. 25.
    Sampedro D (2011) Computational exploration of natural sunscreens. Phys Chem Chem Phys 13:5584–5586CrossRefGoogle Scholar
  26. 26.
    26) Salvador A, Chisvert A (2007) UV filters in sunscreens and other cosmetics tanning and whitening agents analytical methods. In: Salvador A, Chisvert A (eds) Analysis of cosmetic products. Elsevier, Amsterdam, pp 84–120Google Scholar
  27. 27.
    Shaath NA (2010) Ultraviolet filters. Photochem Photobiol Sci 9:464–469CrossRefGoogle Scholar
  28. 28.
    Smith GJ, Miller IJ (1998) The effect of molecular environment on the photochemistry of p-methoxycinnamic acid and its esters. J Photochem Photobio A 118:93–97CrossRefGoogle Scholar
  29. 29.
    Huong SP, Andrieu V, Reyner J-P, Rocher E, Fournneron J-D (2007) The photoisomerization of the sunscreen ethylhexyl p-methocy cinnamate and its influence on the sun protection factor. J Photochem Photobiol A 186:65–70CrossRefGoogle Scholar
  30. 30.
    Wavefunction Inc (2010) Spartan’10. Irvine, CAGoogle Scholar
  31. 31.
    Halgren TA (1996) Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J Comp Chem 17:490–519CrossRefGoogle Scholar
  32. 32.
    Becke AD (1988) Density-functional exchange-energy approximation with correct asymptotic-behavior. Phys Rev A 38:3098–3100CrossRefGoogle Scholar
  33. 33.
    Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785–789CrossRefGoogle Scholar
  34. 34.
    Miehlich B, Savin A, Stoll H, Preuss H (1989) Results obtained with the correlation-energy density functionals of Becke and Lee, Yang and Parr. Chem Phys Lett 157:200–206CrossRefGoogle Scholar
  35. 35.
    Perdew JP (1986) Density-functional approximation for the correlation energy of the inhomogeneous electron gas. Phys Rev B 33:8822–8824CrossRefGoogle Scholar
  36. 36.
    Handy NC, Cohen AJ (2001) Left-right correlation energy. Mol Phys 99:403–412CrossRefGoogle Scholar
  37. 37.
    Hoe W-M, Cohen A, Handy NC (2001) Assessment of a new local exchange functional OPTX. Chem Phys Lett 341:319–328CrossRefGoogle Scholar
  38. 38.
    Perdew JP, Burke K, Ernzerhof M (1996) Generalized gradient approximation made simple. Phys Rev Lett 77:3865–3868CrossRefGoogle Scholar
  39. 39.
    Perdew JP, Burke K, Ernzerhof M (1997) Errata: Generalized gradient approximation made simple. Phys Rev Lett 78:1396CrossRefGoogle Scholar
  40. 40.
    McLean AD, Chandler GS (1980) Contracted Gaussian-basis sets for molecular calculations 1 2nd row atoms, Z = 11-18. J Chem Phys 72:5639–5648CrossRefGoogle Scholar
  41. 41.
    Raghavachari K, Binkley JS, Seeger R, Pople JA (1980) Self-consistent molecular orbital methods 20 basis set for correlated wave-functions. J Chem Phys 72:650–654CrossRefGoogle Scholar
  42. 42.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JJA, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2004) Gaussian 03. Gaussian Inc., Wallingford CTGoogle Scholar
  43. 43.
    Tomasi J, Mennucci B, Cammi R (2005) Quantum mechanical continuum solvation models. Chem Rev 105:2999–3093CrossRefGoogle Scholar
  44. 44.
    Humphrey W, Dalke A, Schulten K (1996) VMD—visual molecular dynamics. J Mol Graphics 14:33–38CrossRefGoogle Scholar
  45. 45.
    Clayden JP, Greeves N, Warren S, Wothers PD (2001) Organic chemistry, 1st edn. University Press, OxfordGoogle Scholar
  46. 46.
    McCormick TM, Bridges CR, Carrera EI, DiCarmine PM, Gibson GL, Hollinger J, Kozycz LM, Seferos DW (2013) Conjugated polymers: evaluating DFT methods for more accurate orbital energy modeling. Macromolecules 46:3879–3886CrossRefGoogle Scholar
  47. 47.
    Promkatkaew M, Suramitr S, Karpkird T, Ehara M, Hannongbua S (2013) Absorption and emission properties of various substituted cinnamic acids and cinnamates, based on TDDFT investigation. Int J Quantum Chem 113:542–554CrossRefGoogle Scholar
  48. 48.
    Bernerd F, Vioux C, Asselineau D (2000) Evaluation of the protective effect of sunscreens on in vitro reconstructed human skin exposed to UVB or UVA irradiation. Photochem Photobiol 71:314–320CrossRefGoogle Scholar
  49. 49.
    More BH, Sakharwade SN, Tembhurne SV, Sakarkar DM (2013) Evaluation of sunscreen activity of cream containing leaves extract of Butea monosperma for topical application. Int J Cosmetic Sci 3:1–6Google Scholar
  50. 50.
    Promkatkaew M, Suramitr S, Karpkird T, Wanichwecharungruang S, Ehara M, Hannongbua S (2014) Photophysical properties and photochemistry of substituted cinnamates and cinnamic acids for UVB blocking: effect of hydroxy, nitro, and fluoro substitutions at ortho, meta, and para positions. Photochem Photobiol Sci 13:583–594CrossRefGoogle Scholar
  51. 51.
    Hayashi M, Nakamura Y, Higashi K, Kato H, Kishida F, Kaneko H (1999) Quantitative structure-activity relationship study of the skin irritation potential of phenols. Toxicol In Vitro 13:915–922CrossRefGoogle Scholar
  52. 52.
    Smith JS, Macina OT, Sussman NB, Luster MI, Karol MH (2000) A robust structure-activity relationship (SAR) model for esters that cause skin irritation in humans. Toxicol Sci 55:215–222CrossRefGoogle Scholar
  53. 53.
    Smith JS, Macina OT, Sussman NB, Karol MH, Maibach HI (2000) Experimental validation of a structure-activity relationship model of skin irritation by esters. Quant Struct-Act Relat 19:467–474CrossRefGoogle Scholar
  54. 54.
    Saliner AG, Patlewicz G, Worth AP (2006) Review of literature-based models for skin and eye irritation and corrosion. Institute for Health and Consumer Protection, Joint Research Centre, European Commission, BrusselsGoogle Scholar
  55. 55.
    Davies MG, Hawk JLM, Rycroft RJG (1982) Acute photosensitivity from the sunscreen 2-ethoxyethyl-p-methoxycinnamate. Contact Dermatitis 8:190–192CrossRefGoogle Scholar
  56. 56.
    Murphy GM, White IR (1987) Photoallergic contact dermatitis to 2-ethoxyethyl-p-methoxycinnamate. Contact Dermatitis 16:296CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Ricardo D’A. Garcia
    • 1
  • Vinícius G. Maltarollo
    • 1
  • Káthia M. Honório
    • 2
    • 3
  • Gustavo H. G. Trossini
    • 1
    Email author
  1. 1.Department of Pharmacy, Faculty of Pharmaceutical SciencesUniversity of São PauloSão PauloBrazil
  2. 2.School of Arts, Sciences and HumanitiesUniversity of São PauloSão PauloBrazil
  3. 3.Center of Natural and Human SciencesFederal University of ABCSanto AndréBrazil

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