Conformational analysis of vitamin K1 model molecule: a theoretical study

Abstract

Isomerism, conformations, and molecular structure of a model molecule of vitamin K 1 with a truncated side chain have been studied by the density functional theory calculations using B3LYP method and double-and triple-f correlation consistent basis sets. The conformations of two possible (E and Z) isomers, formed by the rotations around three single C-C bonds closest to the naphthoquinone ring, have been studied. The lowest energy conformers are stabilized by additional hydrogen bonds between hydrogen atoms of the side chain and an oxygen atom in the naphthoquinone subunit. It is interesting to note that the structure of the energetically preferred conformer of the E-isomer (3c) has been found to be similar to the solid state structures of phylloquinones in the photosystem I of cyanobacterium Synechococcus elongatus. The excited electronic states of two lowest energy conformers have also been investigated.

Investigating Substrate Analogues for Mycobacterial MenJ: Truncated and Partially Saturated Menaquinones

“…Molecular conformations are significant for manifesting physical and chemical reactivity as well as recognition in biological systems. MKs contain alkyl side chains of varying lengths, and conformations have been reported for various alkanes, alkenes, and fatty acids, which all contain alkyl chains of varying lengths. − For example, the degree of folding of C 5 –C 32 n -alkanes in solution depends on the strength of the dispersion force of the solvent and increases with an increase in chain length. − Furthermore, studies of n -hexane and n- pentane in various solvents suggested that the solvent environment had only minor effects on the conformational equilibrium . Interestingly, conformations observed in polar and spherical solvents such as dimethyl sulfoxide (DMSO) favored gauche conformations .…”

“…Interestingly, conformations observed in polar and spherical solvents such as dimethyl sulfoxide (DMSO) favored gauche conformations . Computational studies have been carried out on MK analogues in which folded conformations were found to be favorable. , Importantly, we recently reported that menaquinone-2 (MK-2) adopts a folded, U-shaped conformation in solution and within a model membrane interface . However, MK-1 contains only one isoprene unit and presents the best opportunity for a flat–extended conformation to exist, and therefore, it is important to determine if a flat–extended (i.e., trans or extended configuration of the side chain and isoprene planar), folded–extended (i.e., isoprene folded upward), or U-shaped conformation (i.e., isoprene folded up and back toward the naphthoquinone in a U shape) is preferred (see the illustration below).…”

Interplay of thermochemistry and Structural Chemistry, the Journal (volume 22, 2011, issues 1–3) and the discipline

“…The DFT approach was used by Zakharov and Vogt [81] to study the conformations of two possible isomers (E and Z) of vitamin K 1 using a model molecule having one -CH 2 -CH 2 -CH 2 -C(CH 3 ) 2 -sequence of the side chain instead of three in the actual vitamin K 1 molecule. This model provided more valuable information on this bioactive species than any other model used before.…”

Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives

“…We have adopted the simple naming system where MK-2 with a saturated double bond at the second isoprene unit is denoted as menaquinone-2­(II-H 2 ) and abbreviated as MK-2­(II-H 2 ), where II denotes the second isoprene unit and H 2 denotes the saturation of one double bond (Figure B). , This naming system follows for higher degrees of saturation such as MK-2­(I,II-H 4 ), that is, saturated at isoprenes I and II and MK-3­(I,II,III-H 6 ), that is, saturated at isoprenes I, II, and III (Figure C,E). Although MK-2­(II-H 2 ) and menaquinone-3­(II-H 2 ) [abbreviated as MK-3­(II-H 2 )] were known in literature reports mostly in the 1950s − and MK-2­(II-H 2 ) was considered in a computational model study, there are no modern syntheses reported, and these analogues have not been extensively characterized nor have their geometric isomers been resolved and characterized in the literature. Evidence supports the trans MK isomer as the only biologically active isomer .…”