title: Experimental, SOPPA(CCSD), and DFT analysis of substitutent effects on NMR 1JCF coupling constants in fluorobenzene derivatives.
abstract: Interesting insight into the electronic molecular structure changes associated with substituent effects on the Fermi contact (FC) and paramagnetic spin-orbit (PSO) terms of (1)J(CF) NMR coupling constants (SSCCs) in o-X-, m-X-, and p-X-fluorobenzenes (X = NH(2); NO(2)) is presented. The formulation of this approach is based on the influence of different conjugative and hyperconjugative interactions on a second-order property, which can be qualitatively predicted if it is known how they affect the main virtual excitations entering into that second-order property. A set of consistent approximations are introduced in order to analyze the behavior of occupied and virtual orbitals, which define some experimental trends for (1)J(CF) spin-spin coupling constants. In addition, DFT hybrid functionals were used, and a similar degree of confidence to compute the (1)J(CF) with those observed for the SOPPA(CCSD) method was obtained. The (1)J(CF) SSCCs for ezetimibe, a commercially fluorinated drug used to reduce cholesterol levels, were measured and DFT-calculated, and the qualitative approach quoted above was applied. As a byproduct, a possible method to determine experimentally a significant PSO contribution to (1)J(CF) SSCCs is discussed.
authors.affiliation: Chemistry Institute, State University of Campinas, Caixa Postal 6154, 13084-971 Campinas, SP, Brazil.
authors.forename: Janaina Dantas
authors.initials: JD
authors.lastname: Vilcachagua
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Ducati
authors.forename: Roberto
authors.initials: R
authors.lastname: Rittner
authors.forename: Rubén H
authors.initials: RH
authors.lastname: Contreras
authors.forename: Cláudio F
authors.initials: CF
authors.lastname: Tormena