Noncovalent Interactions Of Metal Cations With Nitrogen Heterocycles: Tandem Mass Spectrometry And Theoretical Studies

Nathan Cunningham, Wayne State University






August 2018

Advisor: Dr. Mary T. Rodgers

Major: Analytical Chemistry

Degree: Master of Science

Nitrogen containing heterocyclic (N heterocyclic) molecules are an important class of molecules in a multitude of fields including the biological and chemical disciplines. Interactions between metal cations and N-heterocyclic molecules are common. Understanding the intrinsic noncovalent binding interactions between metal cations and N heterocycles is an important area of study. Several mass spectrometry techniques were utilized to study the structure and energetics of these systems including: threshold collision induced dissociation (TCID), infrared multiple photon dissociation (IRMPD) action spectroscopy, and energy-resolved collision induced dissociation (ER CID). These techniques were used in tandem with electronic structure calculations to provide deeper insight into the structure and binding in these complexes.

TCID was used with complementary theoretical electronic structure calculations to accurately determine the bond dissociation energies (BDEs) of eight alkali metal cation N-heterocycle complexes of the form M+(N L)x, where M+ = Na+ and K+, N L = 2,2′ bipyridine (Bpy) and 1,10 phenanthroline (Phen), and x = 1 2. The primary dissociation process for both the mono and bis ligated complexes involves loss of an intact neutral ligand. The Na+ complexes were determined to have larger BDEs than the K+ complexes, primarily due to the smaller size of Na+ vs K+. The lack of valance electrons and their involvement in the binding leads to smaller BDEs for these complexes than those to the first row transition metal monocations, Ni+, Cu+, and Zn+.

IRMPD action spectroscopy was used in conjunction with theoretical calculations to ascertain the influence of Cu+ and Ag+ cationization on the stable tautomeric conformations of uracil. The experimentally obtained IRMPD spectrum of [Ura+Cu]+ was compared to theoretically predicted spectra for low energy structures in the IR fingerprint region and hydrogen stretching regions. The ground conformer was found to be U1_O4a, establishing Cu+’s preference for binding to the O4 carbonyl. However, bidentate binding to the O2 carbonyl oxygen and the N3 amide nitrogen is also competitive. Similar comparisons for the [Ura+Ag]+ complex find that the ground conformer instead binds via bidentate interaction with the O2 carbonyl and N3 amide atoms, U3a_O2N3. O4 binding is also competitive but, less so than in the case of Cu+. However, the experimental results suggest that both modes of binding occur for both complexes and that O4 monodentate binding is even more favorable for Ag+ than in the case of Cu+.

ER CID and survival yield analyses provide a complementary technique to IRMPD action spectroscopy. Comparing the CID50% values, which correspond to the rf amplitude required to produce 50% dissociation of the precursor ion, the effects of cation binding to uracil can be determined. Information about the fragmentation pathways and relative stabilities of the [Ura+M]+ complexes can also be ascertained. ER CID indicates that stabilization of the minor tautomers of uracil depends on the strength of cation binding. Similar to protonation, Cu+ and Ag+ bind strongly enough to induce tautomerization. The sodium cation exhibits the weakest binding of the four cations such that tautomerization is not induced in the uracil moiety. While Ag+ is able to induce tautomerization of uracil, the binding is not sufficiently activating to produce fragmentation except via simple noncovalent dissociation. The [Ura+Cu]+ complex binds strong enough that activation of the uracil moiety is preferred over simple noncovalent bond cleavage.