ORIGINAL PAPER Substitution effects in N-pyrazole and N-imidazole derivatives along the periodic table Fernando Blanco Æ Ibon Alkorta Æ Krzysztof Zborowski Æ Jose ´ Elguero Received: 7 June 2007 / Accepted: 21 August 2007 / Published online: 26 September 2007 Ó Springer Science+Business Media, LLC 2007 Abstract A theoretical study of the monosubstitution effects of all the atoms of the second and third row of the periodic table on the pyrazole and imidazole rings has been carried out by means of B3LYP/6-31+G(d,p) DFT calcu- lations. The geometric and electronic properties, calculated using the atoms in molecules methodology, electrostatic potential, and frontier orbitals have been analyzed. Some of the results have been rationalized based on the electro- negativity of the substituents. In addition, the different parameters obtained have been compared with aromaticity indexes (HOMA and NICS). A comparison with the results obtained for the corresponding N-pyrrole derivatives has been carried out. Keywords Pyrazole  Imidazole  Substituent effects  Electrostatic potential  Frontier orbitals  Aromaticity  AIM Introduction The rationalization and understanding of the substitution effects in modern sciences are of utmost importance if one wants to be able to predict organic chemistry reactivity and biological activity of chemical entities. In a recent article, we have studied the influence of all the elements of the first, second, and third row of the periodic table as sub- stituents of benzene and N-pyrrole [1]. Other theoretical studies were devoted, in particular, to the properties of a selection of derivatives of pyrazoles, particularly geome- tries and methyl stabilization energies [2], GIAO calculations [3], and metallotropic transpositions [4]. As a continuation of our previous study [1] and due to the importance of the imidazole and pyrazole rings in chemistry and biology, an extended approach of their properties has been undertaken. Thus, in the present article, the geometrical and electronic properties of pyrazole and imidazole derivatives of all the atoms of the second and third row of the periodic table have been evaluated and compared with those of the corresponding pyrrole deriva- tives. In addition, atomic partition of the energy, charge, and volume of the molecules have been carried out with the atoms in molecules (AIM) methodology. The electrostatic potential and frontier orbital profiles have been analyzed. Finally, two aromaticity indexes have been evaluated and compared with the geometrical and electronic properties previously considered. Methods The geometry of the molecules has been fully optimized with the hybrid HF/DFT method, B3LYP [5, 6], and the 6- 31+G(d,p) basis set [7] using the ultrafine grid option and the Berny algorithm with the default parameters of the Gaussian-03 package [8]. Frequency calculations have been carried out at the same computational level to confirm that the structures obtained correspond to energetic minima. The electron density of the molecules has been analyzed with the AIM methodology [9] and the AIMPAC program F. Blanco  I. Alkorta (&)  J. Elguero Instituto de Quı ´mica Me ´dica (C.S.I.C.), Juan de la Cierva, 3, Madrid 28006, Spain e-mail: ibon@iqm.csic.es K. Zborowski Faculty of Chemistry, Jagiellonian University, 3 Ingardena Street, Krakow 30-060, Poland 123 Struct Chem (2007) 18:965–975 DOI 10.1007/s11224-007-9237-z