version date: 1 December 2006 SPARTAN is a program that embraces molecular mechanics as well as ab initio and semiem- pirical molecular orbital and density functional methods. SPARTAN is intended to provide a con- venient environment to carry out individual molecular mechanics calculations, molecular orbital calculations, and density functional calculations on diverse molecular systems SPaRTaN Presently comprises seven independent program modules: a graphical user interface and ab initio, density functional, semi-empirical, mechanics, properties, and graphics modules SPARTAN'S architecture makes a clear separation between tasks and methods. Tasks indicate what is to be done(e.g, perform a geometry optimization or search conformational space), while methods dictate how the tasks are to be done(e. g use MMFF molecular mechanics or the Pm3 semiempirical method ) Both tasks and methods are specified in the graphical user interface SPARTAN'S graphical user interface provides a number of functions, among them: construction and editing of molecular structures, preparation of input designating the quantum chemical or mo- lecular mechanics calculation to be performed by the ab initio, density functional, semiempirical or mechanics modules; the preparation of input for Gaussian 94, preparation of input designating molecular properties to be calculated using the properties module SPARTANS ab initio module provides for calculation of the energy and wavefunction for a given nuclear configuration, of equilibrium or transition-state geometries and of normal-mode vi- brational frequencies. The module is presently limited to Hartree-Fock and MP2 correlated models, for both closed- and open-shell systems. SPARTAN'S semi-empirical module provides for the cal culation of heats of formation, equilibrium, and transition-state geometries and normal-mode vi- brational frequencies, as well as for searching of conformation space of both acyclic and cyclic molecules. The MNDO(Modified Neglect of Differential Overlap), AMl, and PM3 models are supported AMI and PM3 Semi-empirical Models Ab initio and semi-empirical models are based on the Hartree-Fock set u Both the para. digms"are strongly rigorous in regards to the solution of the Schrodinger but significant approximations are made to make the semi-empirical methods faster than their ab initio counter- parts. Semi-empirical methods are simplified versions of the Hartree-Fock theory using empirical methods that are derived from experimental data corrections in order to improve performance These methods are usually referred to through acronyms encoding some of the underlying theoreti cal assumptions. The most frequently used methods(MNDO, AMl, PM3)are all based on the Ne glect of Differential Diatomic Overlap(NDDO) integral approximation, while older methods use simpler integral schemes such as CNDO and INDO. all the three approaches belong to the class of Zero Differential Overlap(ZDO)methods, in which all two-electron integrals involving two-center charge distributions are neglected. A number of additional approximations are made to speed up calculations, and a number of parameterized corrections are made in order to correct for the ap- such that the calculated energies are expressed as heats of formations instead of total energia orme o proximate quantum mechanical model. How the parameterization is performed characterizes particular semi-empirical method. For MNDO, AMl, and PM3, the parameterization is performed Both AMI (Austin Model 1)and PM3 ( Parameterization Method 3 )are based on the basic nddo theory by Michael Dewar at the University of Texas, Austin. The substantial difference between the two methods is in the parameters used to partly replace the full ab initio implementation of the Hartree-Fock theory and in the less pronounced chemical sense of the PM3 model, built on a largely undirected mathematical optimization process, when compared to AMI. The stronger chemical character of the AMl method reflects on the better external performing of its parameters that is, the capability to yield useful results for situations not specifically included in the molecular basis set for parameterization(MBSP). Generally, AMI represents differences between compounds more reliably. PM3 works very well, for instance, when nitro-derivatives, extensively parameter ized in the MBSP, are calculated. PM3 performs sometimes better for geometries that are guessed <www.iupac.org/publications/cd/medicinalchemistry6 SPARTAN is a program that embraces molecular mechanics as well as ab initio and semiem￾pirical molecular orbital and density functional methods. SPARTAN is intended to provide a con￾venient environment to carry out individual molecular mechanics calculations, molecular orbital calculations, and density functional calculations on diverse molecular systems. SPARTAN presently comprises seven independent program modules: a graphical user interface and ab initio, density functional, semi-empirical, mechanics, properties, and graphics modules. SPARTAN’s architecture makes a clear separation between tasks and methods. Tasks indicate what is to be done (e.g., perform a geometry optimization or search conformational space), while methods dictate how the tasks are to be done (e.g., use MMFF molecular mechanics or the PM3 semiempirical method). Both tasks and methods are specified in the graphical user interface. SPARTAN’s graphical user interface provides a number of functions, among them: construction and editing of molecular structures, preparation of input designating the quantum chemical or mo￾lecular mechanics calculation to be performed by the ab initio, density functional, semiempirical, or mechanics modules; the preparation of input for Gaussian 94, preparation of input designating molecular properties to be calculated using the properties module. SPARTAN’s ab initio module provides for calculation of the energy and wavefunction for a given nuclear configuration, of equilibrium or transition-state geometries and of normal-mode vi￾brational frequencies. The module is presently limited to Hartree–Fock and MP2 correlated models, for both closed- and open-shell systems. SPARTAN’s semi-empirical module provides for the cal￾culation of heats of formation, equilibrium, and transition-state geometries and normal-mode vi￾brational frequencies, as well as for searching of conformation space of both acyclic and cyclic molecules. The MNDO (Modified Neglect of Differential Overlap), AM1, and PM3 models are supported. AM1 and PM3 Semi-empirical Models Ab initio and semi-empirical models are based on the Hartree–Fock set of ideas. Both the “para￾digms” are strongly rigorous in regards to the solution of the Schrödinger equation, but significant approximations are made to make the semi-empirical methods faster than their ab initio counter￾parts. Semi-empirical methods are simplified versions of the Hartree–Fock theory using empirical methods that are derived from experimental data corrections in order to improve performance. These methods are usually referred to through acronyms encoding some of the underlying theoreti￾cal assumptions. The most frequently used methods (MNDO, AM1, PM3) are all based on the Ne￾glect of Differential Diatomic Overlap (NDDO) integral approximation, while older methods use simpler integral schemes such as CNDO and INDO. All the three approaches belong to the class of Zero Differential Overlap (ZDO) methods, in which all two-electron integrals involving two-center charge distributions are neglected. A number of additional approximations are made to speed up calculations, and a number of parameterized corrections are made in order to correct for the ap￾proximate quantum mechanical model. How the parameterization is performed characterizes the particular semi-empirical method. For MNDO, AM1, and PM3, the parameterization is performed such that the calculated energies are expressed as heats of formations instead of total energies. Both AM1 (Austin Model 1) and PM3 (Parameterization Method 3) are based on the basic NDDO theory by Michael Dewar at the University of Texas, Austin. The substantial difference between the two methods is in the parameters used to partly replace the full ab initio implementation of the Hartree–Fock theory and in the less pronounced chemical sense of the PM3 model, built on a largely undirected mathematical optimization process, when compared to AM1. The stronger chemical character of the AM1 method reflects on the better external performing of its parameters, that is, the capability to yield useful results for situations not specifically included in the molecular basis set for parameterization (MBSP). Generally, AM1 represents differences between compounds more reliably. PM3 works very well, for instance, when nitro-derivatives, extensively parameter￾ized in the MBSP, are calculated. PM3 performs sometimes better for geometries that are guessed <www.iupac.org/publications/cd/medicinal_chemistry/> version date: 1 December 2006