Ligand size distribution of phenanthroline-functionalized polyethylene glycol-iron(II) complexes determined by electrospray ionization mass spectrometry and computer simulation

Abstract

The complex formation in solution, and the gas-phase dissociation of a phenanthrolineterminated poly(ethylene glycol) with Fe 2ϩ ions were investigated. The size distribution of poly(ethylene glycol)-␣-monomethyl--5-[1,10]phenanthroline (mPEG_phen) was determined by electrospray ionization mass spectrometry (ESI-MS). Based on the measured ligand size distribution of mPEG_phen by ESI-MS, the 1:3 complex formation (Fe 2ϩ /mPEG_Phen) was computer-simulated as a pure random assembly process. The simulated distribution fits excellently to that of the complex Fe(mPEG_phen) 3 2ϩ determined from the ESI-MS intensities. In addition, the collision-induced dissociation (CID) of the Fe(mPEG_phen) 3 2ϩ complex was also studied by tandem mass spectrometry (ESI-MS/MS) and by computer simulation, as well. [1] offers a unique tool for the investigation of metal-containing complexes because it overcomes the propensity of these complex ions to dissociate when transferred from solution into the gas phase [2][3][4][5][6][7][8]. In addition, the gas-phase complex ions of interest can then be selected and subjected to collisioninduced dissociation (CID) to promote the detachment of the intact ligands. In this way, the determination of the relative gas-phase stability of the different complex ions is feasible as it has been shown in several papers [6 -9]. Although various types of complexes have been used in several ESI-MS studies, to our knowledge, no ESI-MS report on complexes with ligands consisting of polymer chains has appeared. Since a real polymer is composed of polymer chains with varying chain lengths, it is interesting to study the effect of the chain length on the complex formation and dissociation of these complexes in the gas phase by utilizing the capability of ESI-MS.In this paper, we report the ESI-MS and computer simulation studies of the complex formation of a phenanthroline-functionalized polyethylene glycol with Fe 2ϩ ion and the dissociation of this complex under CID conditions. Experimental MaterialsHPLC grade methanol (Scharlau, Sentmenat, Spain), Mohr's salt (Spektrum 3D, Debrecen, Hungary), sodium trifluoroacetate, and 5,6-epoxy-5,6-dihydro-[1,10]phenanthroline (Sigma-Aldrich, Steinheim, Germany) were used without further purification. Poly(ethylene glycol) 1100 monomethyl ether was purchased from Fluka (Buchs, Switzerland). The structure of poly(ethylene glycol)-␣-monomethyl--5-[1,10]phenanthroline ether (mPEG_ phen) is presented in Scheme 1. The detailed synthesis of mPEG_phen will be described in a separate paper. MethodsElectrospray quadrupole time-of-flight mass spectrometry (ESI-QTOF MS). Measurements were performed with a MicroTOF-Q-type Qq-TOF MS instrument equipped with an ESI source (Bruker Daltonics, Bremen, Germany). The solutions at a concentration of 10 M were introduced directly into the ESI source with a syringe pump (Cole-Parmer Ins. Comp., Vernon Hills, IL, USA) at a 3 L/min flow rate. The Fe(mPEG_phen) 3 2ϩ com-

The influence of molecular design on structure–property relationships of a supramolecular polymer prodrug

“…This value is in good agreement with PEG-phenanthroline compounds reported by Nagy et al. ( 18 , 19 ). Interestingly, the CMC values for PEG–DPCA assemblies do not seem to be directly related to DPCA content ( Table 1 and SI Appendix , Fig.…”

“…DPCA is claimed to act as a competitive inhibitor of the 2-oxoglutarate cofactor that is needed for hydroxylation of HIF-1α by PHD enzymes ( 43 – 45 ). However, DPCA is also capable of ligating to the active iron site within PHD enzymes via the phenanthroline and/or carboxylic acid moieties ( 19 , 45 ). Computational molecular docking of DPCA against HIF hydroxylases has predicted that bidentate iron ligation via the carboxylic acid moiety is preferred, and analogs of DPCA lacking one nitrogen or one pyridine ring exhibit reduced activity ( 41 ).…”

The Influence of molecular design on structure-property relationships of a supramolecular polymer prodrug

“…al. 32,33 Interestingly, the CMC values for PEG-DPCA assemblies do not seem to be directly related to DPCA content (Table 1). This is surprising, as the hydrophobic nature of DPCA is presumed to be the main driving force for self-assembly.…”

“…DPCA is claimed to act as a competitive inhibitor of the 2-oxoglutarate cofactor that is needed for hydroxylation of HIF-1α 12,13,15 . However, DPCA is likely capable of ligating to the active iron site within PHD enzymes via the phenanthroline and/or carboxylic acid moieties 15,33 . Computational molecular docking of DPCA against HIF hydroxylases has predicted that bidentate iron ligation via the carboxylic acid moiety is preferred and analogues of DPCA lacking one nitrogen or one pyridine ring exhibit reduced activity 14 .…”

Structural, Electrical and Optical Properties of Pyrrolo[1,2-i][1,7] Phenanthroline-Based Organic Semiconductors

“…The structure of the compounds (together with the type of substituents) is presented along with their melting points, in Scheme 1 and Table 1 . The products were completely characterized using spectral (IR (Infrared), 1H- and 13C-NMR (Nuclear Magnetic Resonance), Mass Spectrometry) and analytical techniques [ 29 , 30 , 31 ]. Organic compounds under study were synthesized in the form of polycrystalline powders and were found to exhibit good chemical stability in ambient atmospheric environment.…”