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Spectrochimica Acta Part A 75 (2010) 1261–1269Contents lists available at ScienceDirectSpectrochimica Acta Part A: Molecular andBiomolecular Spectroscopyjournal homepage: www.elsevier.com/locate/saaRelationships observed in the structure and spectra of uraciland its 5-substituted derivativesM. Alcolea Palafoxa, G. Tardajosa, A. Guerrero-Martíneza, J.K. Vatsb, Hubert Joec, V.K. Rastogib,∗aDepartamento de Química-Fisica1, Facultad de Ciencias Químicas, Universidad Complutense, Madrid 28040, SpainbDepartment of Physics, C.C.S. University, Meerut 250004, Uttar Pradesh, IndiacPhysics Department, Mar Ivanios College (University of Kerala), Trivandrum, Indiaa r t i c l ei n f oArticle history:Received 7 July 2009Received in revised form 6 November 2009Accepted 8 December 2009Keywords:5-Substituted uracilIR and Raman spectraVibrational wavenumbersGeometrya b s t r a c tTheeffectsonthegeometrystructure,atomicchargesandvibrationalwavenumbersofthemaindifferentsubstituents in the 5th position of the uracil ring were analysed, and relationships were established.The 5-monosubstituted derivatives studied were 5-XU (X=F, Cl, Br, I, CH3, NH2, NO2). The geometryand vibrational wavenumbers were determined in these molecules. The FT-IR and Raman spectra werestudied with the support of B3LYP calculations using several basis sets. Several general conclusions wereunderlined.© 2010 Elsevier B.V. All rights reserved.1. IntroductionUracil (U) and its derivatives, constituents of the genetic mate-rial, play a fundamental role in basic biological processes. Theimportance of uracil has been indicated by a considerable num-ber of publications appeared in literature from the structure[1–6] and spectroscopic [6–17] point of view. The bioactivity of5-substituted uracils also induces exceptional interest in their bio-chemistryandpharmacology,andtheyarethemostinterestingandstudieduracils.Inthepresentpaperthe5-monosubstitutedderiva-tives of uracils (5-XU) (X=F, Cl, Br, I, CH3, NH2, NO2) have beenstudied.Among 5-XU derivatives special attention has been paid to the5-halogenated uracils (5-XU). Transformation of uracil into 5-XU(X=halogen) significantly changes its chemical and spectroscopicproperties, as well as its in vivo activity. Halogenated pyrimidinesweresynthesizedinthe1950saspotentialantitumoragentsduetothe substitution of uracil or thymine into RNA or DNA by 5-XU per-turbs the replication of nucleic acids. 5-XU derivatives have beenalso tested against HIV [18], and they are also chelating agents inmetalcomplexesanalogoustothosewhereuracilplaysaligandrole[19–27]. There are also well-known metal complexes with adenineas primary ligand and a halouracil as secondary ligand [28]. 5-XUchangeinteractionofnucleicacidwithproteinsbyinducingvariousbiological phenomena [21]. They have served also as repair system∗Corresponding author. Tel.: +91 120 2780506.E-mail address: v krastogi@rediffmail.com (V.K. Rastogi).models to study damaged DNA [22]. The biology and chemistry of5-XU have been explored as a possible means of sensitizing DNAto ionizing radiation [23–25]. Their electron affinities, greater thanthose of other nucleic acid bases, make them capture electrons anddehalogenate;however,theirradiosensitizationpropertiesarelesseffective in double-stranded than in single-stranded DNA [24]. Sofar,radiosensitizationof5-XUhavenotbeenutilizedclinically[26].Considering the importance of 5-XU for medicinal chemistry,their vibrational spectra, taken in low-temperature matrices andin the polycrystalline state, have been relatively little looked into.Several authors have investigated the vibrational spectra for bothAr-matrix and for the solid state [29–38], and the theoretical andexperimental1H,13C,15N,17O NMR spectra [39].Among 5-XU, 5-fluorouracil (5-FU) (first introduced intomedicine in 1957) is widely recognized today as effective treat-ment modalities, especially with tumors of the head, neck andbreast [26,40–42], and in combination drug regimens for cancerchemotherapy. It has been widely used in the treatment of cancer[18,43–45], and it exhibits also an antibacterial activity [46], andaugments the bactericidal effect of antibiotics [47]. The other 5-XUhave exhibited a weaker antiviral and antibacterial activity thanthat of 5-FU [48].Chlorinated pyrimidines are effective mutagens, clastogensand toxicants, as well as extremely effective inducers ofsister-chromatid exchanges [26]. 5-Chlorouracil (5-ClU) has alsoantitumor activity and forms complexes with some metal (II) ions[49]. It has been suggested that peroxidases secreted by humanphagocytes facilitate the formation of 5-ClU and 5-bromouracils(5-BrU) in the human inflammatory tissue [50,51].1386-1425/$ – see front matter © 2010 Elsevier B.V. All rights reserved.doi:10.1016/j.saa.2009.12.042