Syntheses and monolayer properties of vitamin B12 derivatives with seven alkyl chains

The heptapropyl and heptaoctyl esters of vitamin B12 derivatives with a Co(II) or Co(III) center have been synthesized and their monolayer properties have been investigated. The effect of the estersʹ chain length on stability and orientation of the vitamin B12 in a lipid monolayer is discussed on the basis of their surface pressure molecular area (π-A) isotherms. Their isotherms significantly depend on the length of the side chains regardless of the oxidation state of the center cobalt. The isotherm of the heptaoctyl derivatives has a relatively steep shape with a molecular area of ca. 3 nm2 which is fairly close to the molecular area estimated by molecular modeling for face-on orientation. In contrast, the heptapropyl derivatives showed unstable characteristics with collapsing even at low pressures. The heptaoctyl derivatives can also be stably incorporated in the DPPC matrix monolayer, while the heptapropyl derivatives were squeezed out from the same matrix upon compression at high pressures. The effect of coordination of the center cobalt to the matrix lipid was also investigated. Mixing of the heptapropyl Co(II) derivatives with a lysine-functionalized lipid significantly improved the preservation of the vitamin B12 function in the monolayer due to coordination of the lysine amino group to the open axial position of Co(II). The obtained results in this study indicate that stable accommodation of the vitamin B12 functions in the lipid assembly can be achieved by the introduction of a long chain and/or coordination to the matrix lipid. The present study is the first example of a monolayer system of vitamin B12 mimics with a core structurally identical to the naturally occurring one.