A measurement of the proton-proton cross section at the CERN ISR

We present a measurement of the total cross section σ_t in proton-proton collisions at the CERN ISR. The method involves determination of the total interaction rate and machine luminosity. A two-arm scintillation hodoscope observes ～ 90% of the total interaction rate, while a streamer chamber is employed for event topologies missed by the main trigger. An increase of about 10% in σ_t is observed in the energy range √s = 23.6 to √s = 62.8 GeV/c in agreement with previous experiments.     

A Bioresistant Nitroxide Spin Label for In‐Cell EPR Spectroscopy: In Vitro and In Oocytes Protein Structural Dynamics Studies

Approaching protein structural dynamics and protein–protein interactions in the cellular environment is a fundamental challenge. Owing to its absolute sensitivity and to its selectivity to paramagnetic species, site‐directed spin labeling (SDSL) combined with electron paramagnetic resonance (EPR) has the potential to evolve into an efficient method to follow conformational changes in proteins directly inside cells. Until now, the use of nitroxide‐based spin labels for in‐cell studies has represented a major hurdle because of their short persistence in the cellular context. The design and synthesis of the first maleimido‐proxyl‐based spin label (M‐TETPO) resistant towards reduction and being efficient to probe protein dynamics by continuous wave and pulsed EPR is presented. In particular, the extended lifetime of M‐TETPO enabled the study of structural features of a chaperone in the absence and presence of its binding partner at endogenous concentration directly inside cells.     

A comparison of accurate mass techniques for the structural elucidation of fluconazole

Mass spectrometry plays a major role in the structural elucidation and characterisation of drug candidates and related substances. Accurate mass data allow the mathematical prediction of molecular formula of both precursor and fragment ions. In this paper, a comparison of the accurate mass data obtained for the fragmentation of fluconazole, an antifungal drug, by three different methods is made: electron ionisation (EI) using a magnetic sector instrument; electrospray ionisation (ES) using a Fourier transform ion cyclotron mass spectrometer (FTICRMS); and ES using a quadrupole-time-of-flight mass spectrometer (Q-ToF). It is clear from the data obtained that mass accuracy is not simply a function of instrument resolution. The subtle differences observed between collisionally activated dissociation (CAD) and sustained off-resonance collisionally activated dissociation (SORI-CAD) spectra are explained as a consequence of the excitation process. The advantages and disadvantages of the three techniques are discussed within the context of structural elucidation.     

Investigation of the S<Subscript>0</Subscript>S<Subscript>1</Subscript> excitation in bacteriorhodopsin with the ONIOM(MO:MM) hybrid method

 We have investigated the S₀ and S₁ electronic states in bacteriorhodopsin using a variety of QM/MM levels. The decomposition of the calculated excitation energies into electronic and electrostatic components shows that the interaction of the chromophore with the protein electric field increases the excitation energy, while polarization effects are negligible. Therefore, the experimentally observed reduction in excitation energy from solution phase to protein environment (the Opsin shift) does not come from the electrostatic interaction with the protein environment, but from either the interaction ofthe chromophore with the solvent or counter ion, or structural effects. Our high-level ONIOM(TD– B3LYP:Amber) calculation predicts the excitation energy within 8 kcal/mol from experiment, the discrepancy probably being caused by the neglect of polarization of the protein environment. In addition, we have shown that the level of optimization is extremely critical for the calculation of accurate excitation energies in bacteriorhodopsin. Received: 13 October 2001 / Accepted: 6 September 2002 / Published online: 3 February 2003 Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American Chemical Society, 2001 Correspondence to: K. Morokuma e-mail: morokuma@emory.edu     

Theoretical evidence for bound electronic excited states of ozone

Extensive configuration interaction calculations (up to 1532 spin eigenfunctions) have been carried out on ozone with both minimal and extended bases. Vertical and adiabatic excitation energies to 14 excited states are reported, including seven states with vertical excitation energies less than 4 eV. Our calculations indicate that in addition to the ground state there are four other states of ozone (³B₂, ³A₂, ¹A₂ and ³B₁) bound with respect to dissociation to ground state O₂ and O (by 0.4, 0.3, 0.1 and 0.0 eV, respectively). With such small bonding energies, the current results cannot be said to show definitively (except perhaps for ³B₂) these four states to be bound with respect to O₂ + O. However, the theoretical evidence is sufficiently strong as to warrant careful experimental studies. Such bound excited electronic states could play important roles in the chemistry of the upper atmosphere and in the chemistry of oxygen discharge systems. One (or more) of these states may be responsible for the short-lived intermediate (‘ozone precursor’) recently observed in oxygen radiolysis.     

LARGE MUTAGENIC LESIONS ARE INDUCED BY PHOTODYNAMIC THERAPY IN MURINE L5178Y LYMPHOBLASTS*

Abstract— Mutagenic lesions at the thymidine kinase locus (tk) in mouse lymphoma L5178Y (LY) cells treated with red light and either Photofrin (PF) or chloroaluminurn phthalocyanine (AIPc) as the photosensitizer were compared in the relatively photodynamic therapy (PDT)-sensitive strain LY-R16 and the relatively resistant strains LY-S1 and LY-SR1. Southern blot analysis revealed that 92% (36/39) of the PDT-induced thymidine kinase (TK ^?/-) mutants of strains LY-R16 and LY-SR1 lost the entire active tk allele. (Strain LY-S1 lacks a known tk polymorphism and has not been analyzed for loss of the active tk allele.) A decrease in galactokinase (GK) activity in the TK^?/- mutants has been taken as an indication that the mutagenic lesion extends from the tk gene to the closely linked galactokinase gene (gk). Using PF as the photosensitizer, GK activity was decreased in 45% of the LY-R16 mutants and in 22% of the LY-S1 and LY-SR1 mutants. With photoactivated AIPc, 59% of the TK ^?/- mutants of strains LY-S1 and LY-SR1 showed GK inactivation. (LY-R16 mutants were not analyzed because of the low LY-R16 mutant frequency induced by PDT with AlPc.) Thus, many of the TK^?/- mutants of LY cells induced by PDT with either PF or AlPc harbor multilocus lesions.     

Transition States of Binap–Rhodium(I)‐Catalyzed Asymmetric Hydrogenation: Theoretical Studies on the Origin of the Enantioselectivity

By using the hybrid IMOMM(B3LYP:MM3) method, we examined the binap–Rh^I‐catalyzed oxidative‐addition and insertion steps of the asymmetric hydrogenation of the enamide 2‐acetylamino‐3‐phenylacrylic acid. We report a path that is energetically more favorable for the major enantiomer than for the minor enantiomer. This path follows the “lock‐and‐key” motif and leads to the major enantiomeric product via an energetically favorable binap–dihydride–Rh^III–enamide complex. Our theoretical results are consistent with the mechanism that takes place via Rh^III dihydride formation, that is, oxidative addition of H₂ followed by enamide insertion.     

CASSCF calculations for photoinduced processes in large molecules: Choosing when to use the RASSCF, ONIOM and MMVB approximations

In this article, we compare and contrast the RASSCF, ONIOM and MMVB electronic structure methods for calculating relaxation paths on potential energy surfaces of the excited states of large molecules, and for locating any resulting conical intersections at which nonadiabatic decay can take place. Each method is treated here as an approximation to CASSCF, which we choose as our reference level of theory, but which becomes prohibitively expensive computationally for large molecules. Both MMVB and ONIOM are hybrid computational methods – combining different levels of theory in an energy plus derivatives calculation at a particular molecular geometry – but they differ fundamentally in that MMVB is a hybrid-atom method, whereas ONIOM is a hybrid-molecule method. We explain this distinction through four representative applications: the photostability of pyracylene (studied with CASSCF, RASSCF, MMVB); large geometry changes in the singlet excited states of triangulene (studied with MMVB); a model for interstitial nickel defects in a synthetic diamond lattice (studied with ONIOM CAS:UFF); and the photochemical [4 + 4] cycloaddition of cyclohexadiene to naphthalene (studied with ONIOM CAS:MMVB). We show that each method is more appropriate for a particular type of photochemical problem. This article is part perspective, part review, and contains new results for three multi-state or photoinduced processes in complex systems.