Making use of a combination of ab initio calculated geometries, orbital energies, and orbital spatial distributions as well as experimental information about bond lengths, bond energies, vibrational frequencies, and dipole moments, the nature of the terminal PO bond in phosphates such as (MeO)(3)PO was probed and compared to the case in MeO-P=O where P is trivalent and a PO pi bond is thus assumed to exist. We find that the MeO-P and terminal PO bond lengths in (MeO)(3)PO are essentially the same as in MeO-P=O and the terminal PO lengths are substantially shorter than single P-OMe bond lengths. We also find that the HOMO orbital energies in the two compounds are within 0.1 eV of one another and that these orbitals have spatial characteristics much like one would expect of a bonding pi orbital connecting two atoms from different rows of the periodic table. Using this data, making a comparison to the more familiar bonding arising in N(2), CO, and BF, and taking note of the dipole moments in compounds known to possess dative bonds, we conclude that it is best to represent the terminal PO bond in phosphates in terms of valence-bond structures such as (MeO)(3)P=O in which the formal charges are P(0)O(0) and where a single PO pi bond exists. However, when it comes to characterizing the PO antibonding pi* orbitals, significant differences arise. Electronic structure methods were able to identify the pi* orbital of MeO-P=O and to determine its energy (the MeO-P=O(-) anion is even bound). Similar attempts to identify the PO pi* orbital in the unbound (MeO)(3)P=O(-) anion lead us to conclude that this anion state is probably so strongly coupled to the continuum (i.e., to states corresponding to (MeO)(3)P=O plus a free electron) that it is so short lived as to be undetectable in experiments.

Ab initio electronic structure calculations have been performed on two model systems containing a disulfide linkage and one or two positively charged sites, aimed at gaining further insight into how and where electrons attach to positively charged peptides under electron capture (ECD) and electron transfer dissociation (ETD) mass spectroscopy conditions. Couplings among electronic states involving (i) an entrance-channel with the excess electron residing on a donor anion interacting with the positively charged peptide, (ii) a state in which the electron has been transferred to the SS sigma* orbital to cause bond cleavage, and (iii) a manifold of states in which the electron has been transferred to a ground- or excited-Rydberg orbital on a positive site. The results of this study suggest that specific excited Rydberg states play a key role in effecting electron shuttling to the SS sigma* orbital. The excited-Rydberg orbitals close in energy to the SS sigma* orbital and with sufficient radial extent to span the distance between the positive site and the SS sigma* orbital play the key role. Then, when the anion donor, excited-Rydberg, and SS sigma* orbitals achieve spatial proximity and similarity in energies, one can have what is termed here a shuttle of an electron from the donor to the SS sigma* orbital, which results in SS bond cleavage. For the singly and doubly charged systems studied here, it was the 3p and 3d Rydberg orbitals, respectively, that met these criteria of spatial and energetic proximity. For other peptides having different charge states, it will be other Rydberg orbitals that meet these criteria because the relative energies of the SS sigma* and Rydberg orbitals are governed by the (different) Coulomb stabilizations these orbitals experience. However, the evidence suggests that it is not very high-energy Rydberg states but states with 3 < n < 10 that are involved in the rate limiting steps in ECD, ETD, and ECID experiments. (C) 2009 Elsevier B.V. All rights reserved.

Earlier work from this group has suggested that, in electron capture and electron-transfer mass spectrometry experiments on positively charged gas-phase samples of polypeptides, the initial electron attachment event most likely occurs at one of the peptide's positively charged sites (e.g., protonated side chains), although electron attachment can occur at a disulfide or amide site ca. 1-10% of the time. Focusing on the 90-99% dominant channel in which initial electron attachment occurs at a positive site, this paper addresses to what extent and over what distances electron transfer can take place from a positively charged site to a disulfide sigma* or amide pi* orbital, because it is thought that it is through such orbitals that disulfide or N-C(alpha) backbone bond cleavage occurs. Ab initio electronic structure calculations show that, as long as an SS sigma* (or OCN pi*) orbital experiences sufficient Coulomb stabilization from proximal positively charged groups, there are a myriad of excited Rydberg states located on positive sites that are able to induce such intrapeptide electron transfer. Computational data show that the transfer rates decay exponentially with distance for a given Rydberg orbital. An analytical model is developed that allows us to estimate the rates of Rydberg-to-valence and Rydberg-to-Rydberg electron transfers as functions of the Rydberg orbitals' n quantum numbers. This model suggests that transfer can occur over very long distances at rates that are more than competitive with the rates of radiationless relaxation within the manifold of Rydberg states (the latter processes eventually terminate the electron-transfer process an thus the disulfide or N-C(alpha) bond cleavages), and it gives formulas for how these rates depend on n (and thus the radial span of the Rydberg orbitals).

The electron capture dissociation (ECD) of [Mg(H2O)(n)](2+) clusters is examined using ab initio electronic structure methods to interpret experimental data on [Mg(H2O)(n)](2+) and [Ca(H2O)(n)](2+). Calculations are performed on Mg2+(H2O)(n) clusters containing a full first hydration shell plus one or two additional water molecules positioned to represent second- and third-shell molecules. The propensity of the Mg-containing clusters to undergo fragmentation primarily into [Mg(H2O)(n-m)](1+) + mH(2)O (m = 10) for n > 17 but primarily into [Mg(OH)(H2O)(n-k)](1+) + H + (k-1) H2O (k-1 = 10) for n < 17 (for Ca-containing clusters, the transition occurs near n = 22) is rationalized in terms of a model in which:a. For Mg with n < 17 (<22 for Ca), the second hydration shell is not filled, so electron attachment can occur either directly into an O-H sigma* orbital of a first-shell water molecule or into a Rydberg orbital surrounding the cluster, after which electron transfer to a first-shell O-H sigma* orbital occurs, liberating an H atom and generating OH-. The experimental observation that 10 water molecules are released is shown to favor a mechanism in which electron attachment to a Rydberg orbital occurs first and is followed by transfer to an O-H sigma* orbital.b. For Mg with n > 17, the second hydration shell is posited to be filled, and it is shown that electron attachment to a second-shell water O-H sigma* orbital is unlikely. So, electron attachment to a surface-localized Rydberg orbital of the [Mg(H2O)(n)](2+) cluster takes place in a 5-eV exothermic process that boils off ca. 10 water molecules. No OH- + H is formed in such cases. (C) 2008 Elsevier B.V. All rights reserved.

As part of an on-going effort to probe mechanisms for disulfide and backbone N-C-alpha cleavage under electron capture or electron-transfer dissociation mass spectroscopy conditions, theoretical simulations have been carried out to consider the probabilities thata. an electron initially attached to a protonated amine site on a side chain can migrate (through-bond or through-space) to an S-S sigma* orbital and thus cause disulfide cleavage;b. an electron initially attached to a protonated site might be transferred (through-bond or through-space) to another protonated site or to a fixed-charge positive site thus allowing the electron to migrate throughout charged sites in a multiply charged peptide.The primary findings of this work include:c. charged-site to S-S sigma* orbital through-bond electron transfer can occur at significant probabilities but only over ca. 5 intervening bonds covering up to ca. 15 angstrom;d. through-space electron transfer from protonated sites to protonated sites or from fixed-charge sites to fixed-charge sites can be facile, but between protonated and fixed-charge sites transfer is very slow; to effect the transfers between equivalent sites, the two sites must come within ca. 5 angstrom of one another;e. through-space electron transfer from a protonated or fixed-charge site to an S-S sigma* orbital can occur with reasonable probability but if the two sites come within ca. 5 angstrom of one another.Based on these findings, speculation is offered both to interpret recent findings of the McLuckey group on flexible, triply charged peptides and earlier data from the Marshall group on more rigid, helical, doubly charged peptides, both of which contain disulfide linkages that experiments find to be readily cleaved. (C) 2007 Elsevier B.V. All rights reserved.