How Spherical Are Gaseous Low Charged Dendrimer Ions: A Molecular Dynamics/Ion Mobility Study?

Abstract

The globular shape of gaseous ions, resulting from the ionization of large molecules such as polymers and proteins, is a recurring subject that has undergone a renewed interest due to the advent of Ion Mobility Spectrometry (IMS), especially in conjunction with theoretical chemistry techniques such as Molecular Dynamics (MD). Globular conformations result from a fine balance between entropy and enthalpy considerations. For multiply charged ions isolated in the gas phase of a mass spectrometer, the coulombic repulsion between the different charges tends to prevent the ions from adopting a compact and folded 3D structure. In the present paper, we intimately associate data from IMS experiments and MD simulations to unambiguously access the conformations of dendrimer ions in the gas phase with a special attention paid to the dendrimer structure, the generation and the charge state. Doing so, we here combine a set of structural tools able to evaluate the (non)globular shape of ions based on both experimental and theoretical results. 2 Scheme 2: Structure of a poly(amidoamine) dendrimer of generation 2 with an ethylene diamine core (EDA), or with a cystamine core (CYS) (see in the box). The layers of generation 0 (green), 1 (blue), and 2 (red) are highlighted. Note that generation 0 for PAMAM dendrimers corresponds to the generation 1 for PPI.

Structural Characterization of Dendriplexes In Vacuo: A Joint Ion Mobility/Molecular Dynamics Investigation

“…Again, nearly superimposable CCS distributions are recorded for the dendriplex ions, as shown in Figure , even if the nature of the dendrimer slightly impacts the CCS of the dendriplex ions, with P1 giving smaller CCS than E0. This is consistent with the dendrimer ion CCS determined in a previous study, i.e., 117 and 155 Å 2 for P1 and E0 with a 1+ net charge, respectively . The 6 CCS distributions are also characterized by a high CCS FWHM (Full Width at Half Maximum) around 65–70 Å 2 , probably indicating different ion conformations with close CCS.…”

“…In particular, ion mobility spectrometry (IMS) experiments represent an invaluable analytical method to generate structural data on gas-phase ions . By comparing the measured collision cross sections (CCS) with theoretical CCS obtained on candidate ion structures generated upon MD simulations, description of the gas phase ion structures may be afforded at the molecular level. , The IMS/MD combination requires that the MD parameters and the IMS calibration are adequately set up, and elegant studies on protein ions, synthetic polymers and dendrimers , are reported.…”

On the Conformation of Anionic Peptoids in the Gas Phase

“…Monitoring the CCS evolution of polymer ions all along the molecular mass distribution, that is, plotting the CCS as a function of the degree of polymerization (or of the mass), is often proposed as a way to derive the structural (and physicochemical) properties of polymer ions. ,,− This approach is based on the seminal study conducted by Ruotolo et al that demonstrates that the CCS evolution with regard to the molecular mass of globular (protein) ions can be fitted with the following equation: CCS = A ·DP B , where A and B are fitting parameters . For globular ions that are assumed to be spherical objects, the B parameter is determined to be 2/3, as supported using a geometrical model. ,, We recently demonstrated using molecular modeling on peptoid ions that B critically depends on the mass range of data available for the fitting procedure for non-globular ions . However, it is generally considered that a B parameter >2/3 indicates the presence of extended structures, such as helices for which B = 1 is geometrically expected for infinite helical structures .…”

Helical Peptoid Ions in the Gas Phase: Thwarting the Charge Solvation Effect by H-Bond Compensation

“…A general procedure to analyze series of homologous compounds is to fit the data by a power law of the form Ω = AM B , where M is the molecular mass, B is a parameter that reflects the general shape of the ions, and A reflects the ion density. 34,38,48 For ions that adopt a globular shape in the gas phase (proteins, polymers), parameter B is determined to be around 2/3 (0.66), while parameter A is on average equal to 2.435. 39,48,49 In the present study, we obtain a parameter B of 0.71 and a parameter A of 1.77 (Figure 1B, blue dashed curve), indicating that these ions are less compact than globular ions.…”

“…34,38,48 For ions that adopt a globular shape in the gas phase (proteins, polymers), parameter B is determined to be around 2/3 (0.66), while parameter A is on average equal to 2.435. 39,48,49 In the present study, we obtain a parameter B of 0.71 and a parameter A of 1.77 (Figure 1B, blue dashed curve), indicating that these ions are less compact than globular ions. In a previous study dedicated to Nspe peptoid ions, parameter B was estimated at 0.685, pointing to more compact structures in comparison to the present derivatives.…”