Arginine/2,5-Dihydroxybenzoic Acid Clusters:  An Experimental and Computational Study of the Gas-Phase and Solid-State Systems

Abstract

The 1:1 adduct of arginine with 2,5-dihydroxybenzoic acid (DHB) has been studied in the gas phase and in the solid state. Experimentally, the ionization energy (IE) of the 1:1 cluster was determined by wavelength-dependent laser ionization of clusters formed by seeding DHB and arginine into a supersonic jet expansion. Ionization laser power studies performed at several discrete wavelengths established the upper and lower limits for the 1:1 cluster IE and dissociation energy. Subsequent one-color scanned-wavelength laser ionization studies allowed an experimental establishment of the 1:1 cluster IE of 7.193 eV. A combination of molecular dynamics/simulated annealing calculations on the 1:1 cluster followed by density functional theory geometry optimizations using reasonably large basis sets yielded 15 distinct minima on the potential energy surface, all within 5.2 kcal/mol in energy at the B3LYP/6-311++G(2df,2p)//B3LYP/6-31+G** level. The Boltzmann-averaged IE at the same level is 7.11−7.14 eV, in excellent agreement with experiment. Cocrystals of arginine and DHB have been grown, and the crystal structure has been solved. The dominant intermolecular interaction in the cocrystal is a double hydrogen bond (salt bridge) between the guanidinium group of arginine and the (deprotonated) carboxylate group of DHB. This is exactly the same interaction that is found in the lowest-energy structure of the gas-phase 1:1 adduct. The electronic structure of the solid-state cocrystal has been modeled using a cluster approach.

A comparative computational study of matrix-peptide interactions in MALDI mass spectrometry: the interaction of four tripeptides with the MALDI matrices 2,5-dihyroxybenzoic acid, α-cyano-4-hydroxy-cinnamic acid and 3,5-dihyroxybenzoic acid

“…We observed an assortment of hydrogen bonding arrangements between the tripeptides and the matrices. We found a reduction of the vertical ionization potential in all clusters examined, demonstrating that IP lowering observed in previous studies [4][5][6][7][8]17] is general. The average values of IPs of all conformers for each system excluding the spontaneous ground-state proton transferred clusters are tabulated in Table 1.…”

“…All of these proton transfers involve the guanidine group in the arginine residue, which clearly reflects the high basicity of that residue. Similar behaviour was previously seen in the arginine-2,5-DHB system [6]. Large IP reductions from the free matrices (1.27-1.40 eV) are seen with these clusters.…”

“…Our subsequent study [6] of a 1:1 complex of 2,5-DHB with arginine in the gas-phase and solid-solid state showed that the gas-phase cluster has an ionization potential of 7.19 eV, which is considerably lower than that of the matrix and agreed well with the value obtained by theoretical calculation. Structures obtained by X-ray crystal structure analysis and by theoretical calculations showed that proton transfer occurs upon cluster formation (and before ionization) in the lowest energy cluster, and that the dominant intermolecular interaction is a double hydrogen bond between the guanidinium group of arginine and the deprotonated carboxylic acid group of DHB in both the gas phase and the solid state.…”

“…We have previously studied, from both a computational and experimental perspective, the interaction between the common MALDI matrix 2,5-DHB and small proline clusters [5], the formation of a 1:1 complex of 2,5-DHB with arginine [6], and from a purely computational perspective, the interaction of 2,5-and 3,5-DHB with the tripeptide VPL [7]. In an effort to provide a high quality thermodynamic database for species relevant to MALDI, we have also calculated gas phase acidities (GAs) of all isomers of the DHB radical cation and their neutral species [8], and calculated an extensive series of thermodynamic properties of sinapic acid, ferulic acid and -cyano-4-hydroxycinnamic acid (HCCA), all common MALDI matrices.…”

How Important Is Molecular Rigidity for the Complex Stability of Artificial Host–Guest Systems? A Theoretical Study on Self‐Assembly of Gas‐Phase Arginine

“…Due to its ability to form strong salt bridges, arginine is also an ideal model system to study guanidinium-carboxylate interactions. [12][13][14][15][16] Moreover, the strong non-covalent binding interactions of the guanidinium moiety with anionic groups is the basic concept of a research field trying to mimic biological receptor systems in order to improve ligand-receptor interactions and to understand molecular recognition processes. [17][18] A successful rational design of new artificial receptor systems requires a profound knowledge of all inter-and intramolecular interactions as well as the ability to distinguish between molecular inherent and solvent effects.…”