Synthesis of coordination complexes and the use of X-ray diffraction data towards the development of refinement of occupancy of spherical atoms (ROSA), a new approach for the determination of atomic partial charges

Abstract

Due to population and economic growth, development of synthetic chemical products generated in high selective yields via efficient syntheses is necessary to provide a sustainable future. Oxidizing hydrocarbons with dioxygen is of particular interest because of substrate abundance. Challenges arise in overcoming the high bond dissociation energy of carbon-hydrogen bonds (~410 kJ/mole), selectively targeting non-polar C-H bonds, and activating dioxygen. Enzymes have provided inspiration due to their ability to selectively catalyze reactions in high yields with rates of 20+ orders of magnitude faster than uncatalyzed reactions by lowering activation energy barriers, and by accessing otherwise inaccessible substrates. Enzymatic reaction conditions are not compatible with industrial processing conditions and fully grasping the mechanism of many enzymatic catalysis remains elusive, providing opportunities for growth in the field. This work seeks to (1) develop enzymatic structural mimics and (2) experimentally determine partial atomic charges in molecules to better understand development toward molecular discovery. Inspired by reactive small molecule iron catalysts, a chiral pyridyl amine-based ligand, (R)-1-(pyridin-2-ylmethyl)pyrrolin-2-yl)methanol, was synthesized with an excellent quantitative yield. Efforts were made to synthesize (R)-1-(pyridin-2-ylmethyl)pyrrolidine-2-carbaldehyde for attachment to a rigid bis-amino acid macromolecule scaffold to template an artificial enzyme active site, but proved unsuccessful. Synthetic efforts toward the macrocycle development is discussed within. Subsequently, (R)-1-(pyridin-2-ylmethyl)pyrrolin-2-yl)methanol was repurposed for synthesis of manganese and copper coordination complexes. Bis{[μ-2-methoxy N-(methylpyridyl)-N- pyrrolidine][bis(trimethylsilyl)amido]}Mn(II)Mn(II), Bis{(μ-iodo)[N-(methylpyridyl)-N-pyrrolidinol]}Cu(I)Cu(I), Bis{(iodo)[μ-2-methoxy-N-(methylpyridinyl)-N-pyrrolidine]}Cu(II)Cu(II), and Di[N-(methylpyridyl)-N-pyrrolidinol]}Cu(I) Iodide were synthesized and characterized with X-ray crystallography, ultraviolet-visible spectroscopy (UV-Vis), infrared spectroscopy (IR), circular diochroism (CD), nuclear magnetic resonance spectroscopy (NMR), electron paramagnetic resonance spectroscopy (EPR), and elemental combustion analysis. A simple modification to standard refinement techniques of X-ray crystal structures that would allow for the determination of partial atomic charges in single crystal X-ray structures was developed. Existing experimental methods like IR and Raman spectroscopy lack the precision to target individual atoms and density functional theory requires advanced knowledge of computational chemistry. Our simple approach allows for synthetic chemists with knowledge of standard crystallographic software to experimentally model partial atomic charges in compounds with relative ease. The effects of atomic displacement parameters (ADPs) and hydrogen atom position were analyzed to determine which were necessary to most accurately model compound structure. Preliminary results show that hydrogen atoms should be lengthened to realistic distances and atom positions should be fixed prior to partial occupancy refinement. Non-hydrogen ADPs should be re-refined and hydrogen ADPs should remain tied to their respective non-hydrogen atoms during partial occupancy refinement. This modified method demonstrates good correlation with more sophisticated methods for partial charge determination and gives reproducible values for 4-(dimethylamino)pyridine and tetraphenyltin(IV). Determination of partial atomic charges is important for understanding molecular properties, colligative properties, and host-guest interactions.