We report DFT calculations at the B3LYP/D95(d,p) level on the gas phase, aqueous solvation and solvated energies as functions of the central psi and phi dihedral angles (in steps of 5 degrees each) of acetyl-(L)Ala-(L)Ala-(L)Ala-NH(2) (3AL) and its diastereomer, acetyl-(L)Ala-(D)Ala-(L)Ala-NH(2) (3AD). In addition to structures without internal H-bonds (C(5) interactions are neglected), many (95) structures containing internal H-bonds were completely optimized. The only minima for non-H-bonding structures in the gas phase correspond to extended beta-strands for both diastereomers. Some (but not all) structures with internal H-bonds are more stable than those without them. The energy landscapes for the solvated species show multiple minima for the non-H-bonding species and a single minimum for the H-bonding species (3(10)-helix), suggesting that the equilibrium conformational mixture in water be composed of the extended beta-strand, polyproline II, 3(10)-helix, and alpha-helix-like (with no H-bonds) conformations which are all within about 1 kcal/mol of each other. Most H-bonding structures are destabilized relative to the non-H-bonding structures in aqueous solution, but some with large dipole moments are not. The large dipole moment of the alpha-helix-like conformation leads to its increased stability in water (vs the gas phase). Significant qualitative and quantitative differences are reported for the energy landscapes of the two diastereomers when one is compared with the mirror image of the other landscape (particularly in the beta-turn region), suggesting that the differences in the energies of the unfolded peptides need to be considered when considering the stabilities of folded peptides and proteins with single amino acid mutations.

Reactions of electronically excited singlet oxygen ( 1 O 2 ) with the radical cations of guanine (9HG •+ ), 9-methylguanine (9MG •+ ), 2′-deoxyguanosine (dGuo •+ ), and guanosine (Guo •+ ) were studied in the gas phase by a combination of guided-ionbeam mass spectrometric measurement of product ions and cross sections as a function of collision energy (E col ) and electronic structure calculations of the reaction potential energy surface (PES) at various levels of theory. No product could be captured in the 1 O 2 reaction with bare 9HG •+ or 9MG •+ , because energized products decayed rapidly to reactants before being detected. To overcome this unfavorable kinetics, monohydrated 9HG •+ •H 2 O and 9MG •+ •H 2 O were used as reactant ions, of which the peroxide product ions were stabilized by energy relaxation via elimination of the water ligand. Reaction cross sections for 9HG •+ •H 2 O and 9MG •+ • H 2 O decrease with increasing E col , becoming negligible above 0.6 eV. This indicates that the reactions are exothermic with no barriers above reactants and the heat of formation of the products is sufficiently large to overcome their water ligand elimination energy (0.7 eV). Peroxide product ions were also detected in the 1 O 2 reactions with unhydrated dGuo •+ and Guo •+ , in which intramolecular vibrational redistribution was able to stabilize oxidation products. 9MG •+ was utilized as a model system to explore the reaction PES for the initial 1 O 2 addition to the guanine radical cation. Calculations were carried out using single-reference ωB97XD, RI-MP2, and DLPNO-CCSD(T) and multireference CASSCF and CASPT2. Although the same PES profile was obtained at different levels of theory, the energies of the mixed open-and closed-shell 1 O 2 reactant and the open-shell reaction intermediates, transition states, and products are sensitive to the theories. By taking into account both static and dynamic electron correlations, the CASPT2 PES has provided the best agreement with the experimentally measured reaction thermodynamics and predicted 8peroxide as the most probable initial oxidation product of the guanine radical cation.

We compare the energies and enthalpies of interaction of three and seven stranded capped polyglycine aggregates in both the pleated and rippled antiparallel and parallel β-sheet structures as well as the collagenic (3-strand) or polyglycine II-like (7-strand) forms using DFT theory at the B3LYP/D95(d,p) level. We present the overall interaction energies as broken down into pure Hbonding between the strands at the geometries they assume in the aggregates and the distortion energies required to achieve those geometries starting from the fully relaxed single strands. While the antiparallel sheets represent the most stable structures for both the three and seven strand structures, the pure H-bonding interactions are the smallest for these structures. The overall interaction energies are dominated by the energy required to distort the relaxed polyglycine strands rather than the H-bonding energies. The antiparallel β-sheet constrained to C s symmetry has a lower enthalpy, but higher energy, of interaction than the fully optimized structure.Polyglycine crystalizes in three forms, polyglycine I (actually a dimorph) and II. Polyglycine I includes two different crystal structures each containing a different type of β-sheet. 1 -5 The structure of polyglycine II (PII) consists of parallel β-sheets oriented 120 degrees to each other.6 , 7 Three of these sheets intersect at each polyglycine strand. Each triad of nearest neighbor strands bears a striking resemblance to collagen, the most abundant protein in the human body. In collagen, the three strands of polyglycine taken from the crystal structure are replaced with strands comprised of triads of XYG (where X and Y can be any amino acid, most often proline and 4-hydroxyproline) and G is glycine. These are connected by H-bonds from the glycines (donors) on one strand to C=O's (acceptors) of the amide couplings on another peptide strand. The 'sheets' each contain only two strands in collagen-like structures. The principal differences between collagen-like structures and PII lie in the inability of collagen to form the infinite pattern of H-bonds normal to the peptide backbone (found in PII) beyond the three strands of the collagenic triple helix, due to a) the lack of N-H donors on the proline and hydroxyproline residues and b) the steric impediments caused by the side chains of all the amino acids except for glycine. Comparison of the PII and collagen structures begs the questions: a) Does the triple helical (XYG) N structure of collagen result from an evolutionary selection against structures that jdannenberg@gc.cuny.edu. Supporting Information Available: Cartesian coordinates for optimized structures, figures illustrating the structures containing three strands and seven stranded sheets with the constrain that the strands be equivalent.. This material is available free of charge via the Internet at http://pubs.acs.org. could form additional H-bonds such as those present in polyglycine? b) How competitive are the PII structures with β-sheets of the same size? While β...