The transferability of extremely localized molecular orbitals M. Sironi * , A. Famulari, M. Raimondi, S. Chiesa Dipartimento di Chimica Fisica ed Elettrochimica and Centro CSRSRC-CNR, UNiver. degli Studi di Milano, Via Golgi 19, 20133 Milan, Italy Received 6 November 1999; accepted 3 January 2000 Abstract Local methods as useful tools for the elucidation of the electronic structure of large molecules are receiving growing attention. These methods permit the definition of ‘local’ orbitals, which can be transferred from one molecule to another. In this paper we show that the simple transfer of extremely localized molecular orbitals, followed by a simple relaxation process, can provide results that are comparable to a fully optimized self-consistent wavefunction. Atomic charges and electrostatic potentials, which are useful properties in the investigation of the interaction between large molecules, are analyzed. The algorithm used to determine extremely localized molecular orbitals, a slight modification of the self-consistent field for molecular interactions (SCF-MI), is briefly reviewed.  2000 Elsevier Science B.V. All rights reserved. Keywords: Transferability; Extremely localized molecular orbital; Electrostatic potentials 1. Introduction The theoretical development of methods that can be applied to the study of large molecules is a challen- ging target for computational chemistry. Such meth- ods are essential to obtain reliable results in fields such as drug design and modeling of new materials. Molecular orbital (MO) methods have always played a prominent role in theoretical chemistry. The double occupancy of the MOs and, consequently, the possibility to treat them as an orthogonal set have allowed the development of many widely known packages, routinely used to perform calculations on molecules of considerable dimension. Despite some impressive applications of available quantum chemis- try programs, the size of systems of biological or pharmaceutical relevance asks for the development of new methods which can be applied to very large molecules. It is well known that the MOs are completely delo- calized on the molecule. Due to the degree of freedom that permits to linearly combine a set of MOs without changing the corresponding wavefunction, the MOs can be transformed into a set of localized orbitals representing well-recognized chemical building blocks such as functional groups, lone pairs and core electrons. The concept of localization can be used as a promising starting point to study large molecules: in fact, we can think of assembling the electronic struc- ture of a large target molecule, using small building blocks corresponding to its different chemical entities. In this approach the use of localized MOs that can be simply transferred is essential; delocalized MOs, on the contrary, must be completely redetermined in the process of building up the target molecule from its constituents. Journal of Molecular Structure (Theochem) 529 (2000) 47–54 0166-1280/00/$ - see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0166-1280(00)00530-3 www.elsevier.nl/locate/theochem * Corresponding author. E-mail address: maurizio.sironi@unimi.it (M. Sironi).