FT-IR and FT-Raman spectra of 5-chlorocytosine: Solid state simulation and tautomerism. Effect of the chlorine substitution in the Watson-Crick base pair 5-chlorodeoxycytidine-deoxyguanosine M. Alcolea Palafox a,b, ⁎, V.K. Rastogi c,d , S.P. Singh c a Nofima AS - the Norwegian Institute of Food, Fisheries and Aquaculture Research, PB 210, N-1431 Ås, Norway b Departamento de Química-Física I, Facultad de Ciencias Químicas, Universidad Complutense, Ciudad Universitaria, Madrid 28040, Spain c Internet Lab, R.D. Foundation Group of Institutions, NH-58, Kadrabad, Modinagar, Ghaziabad, India d Indian Spectroscopy Society, KC 68/1, Old Kavinagar, Ghaziabad 201 002, India abstract article info Article history: Received 26 October 2016 Received in revised form 26 April 2017 Accepted 13 July 2017 Available online 19 July 2017 The laser Raman and IR spectra of 5-chlorocytosine have been recorded and accurately assigned in the solid state using Density functional calculations (DFT) together with the linear scaling equation procedure (LSE) and the solid state simulation of the crystal unit cell through a tetramer form. These results remarkably improve those reported previously by other authors. Several new scaling equations were proposed to be used in related mole- cules. The six main tautomers of the biomolecule 5-chlorocytosine were determined and optimized at the MP2 and CCSD levels, using different basis sets. The relative stabilities were compared with those obtained in cytosine and their 5-halo derivatives. Several relationships between energies, geometric parameters and NBO atomic charges were established. The effect of the chlorine substitution in the fifth position was evaluated through the stability of the Watson-Crick (WC) base pair of 5-chlorodeoxycytidine with deoxyguanosine, and through their vibrational spectra. © 2017 Elsevier B.V. All rights reserved. Keywords: 5-Chlorocytosine 5-Chlorodeoxycytidine Scaling IR Raman Tautomer 1. Introduction Cytosine (in short Cy), also named as 4-amino-2(1H)-pyrimidinone, is a pyrimidine base and a constituent of nucleotides and as such one member of the base pair cytosine-guanine. It also belongs to a group of the most important pyrimidines that play a fundamental role in the structure and function of enzymes and drugs. The importance of Cy and its derivatives is indicated by the considerable number of publica- tions appeared in the bibliography [1–5]. Spectroscopic investigations on nucleic acid base derivatives may help to throw light on their role in biological systems. Halogenated pyrimidines were synthesized in the 1950s as potential antitumor agents [6]. The analysis of many synthetic pyrimidines with interesting biological and physiological properties indicates that the im- portant positions in them are the fifth and the sixth. Chlorinated pyrim- idines are effective mutagens, clastogens and toxicants, as well as extremely effective inducers of sister-chromatid exchanges [6]. Also chlorinated adducts can be mutagenic or perturb DNA-protein [7a]. In the present manuscript, we focus the attention only on the halogen substituent at 5th position in Cy. The bioactivity of 5-halogenated substituted derivatives of Cy induces exceptional interest in their bio- chemistry and pharmacology, and they are among the most interesting and studied molecules. The inclusion of halogen atoms at the fifth posi- tion of the Cy molecule (5-Xcytosine, X = halogen) leads to the charge distribution variation in the molecule and consequently it greatly affects their structural, electronic and vibrational properties, and as well their in vivo activities. E.g. 5-fluorocytosine and its nucleoside show anti-fun- gal, anti-tumor (anti-leukemia) and anti-viral activities [7b–d]. The interest of this manuscript is centered in the antifungal drug 5- chlorocytosine (5-ClC), Fig. 1, in its geometry, tautomerization, vibra- tional wavenumbers, atomic charges and energies, comparing the re- sults with those obtained in Cy molecule and several of its derivatives. Also we are interested in the study of effect of the chlorine atom in its nucleoside 5-chlorodeoxycytidine. 5-ClC molecule has many important medicinal applications: it can be incorporated into mammalian DNA resulting in heritable gene silencing and altered cytosine methylation patterns [8], and it can also be used as hepatitis-B inhibitors. Although this molecule has been extensively studied from the biochemical point of view, however, its structure, tau- tomerism and vibrational spectra have not been completely analyzed, which is the main task of the present work. The spectra have been ana- lyzed previously by Rastogi et al. [9] and Ahmad et al. [10] without any theoretical support, and by Krishnakumar et al. [11,12] using DFT Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 188 (2018) 418–435 ⁎ Corresponding author at: Nofima AS - the Norwegian Institute of Food, Fisheries and Aquaculture Research, PB 210, N-1431 Ås, Norway. E-mail addresses: alcolea@ucm.es (M. Alcolea Palafox), v_krastogi@rediffmail.com (V.K. Rastogi). http://dx.doi.org/10.1016/j.saa.2017.07.018 1386-1425/© 2017 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy journal homepage: www.elsevier.com/locate/saa