Infrared spectroscopy of ozone-water complex in a neon matrix

Matrix isolation infrared spectroscopy has been applied to study an ozone-water complex of atmospheric interest. The complex was identified in the spectral region of three normal modes of ozone and water. Ab initio calculation at MP4(SDQ), QCISD, and CCSD(T) levels indicates the existence of only one stable conformer, which accords with the present experimental result. This conformer belongs to the Cs symmetry group where two molecular planes of ozone and water are perpendicular to the Cs symmetry plane. The binding energy was calculated to be 1.89 kcal/mol at the CCSD(T)/6-311++G(3df,3pd)//CCSD(T)/6-311++G(d,p) level of theory. The formation constant and atmospheric abundance of the ozone-water complex are estimated using the thermodynamic and spectroscopic data obtained.     

Stereoelectronic control in the cleavage of tetrahedral intermediates in the hydrolysis of esters and amides

A new stereoelectronic theory for the cleavage of the tetrahedral intermediate in the hydrolysis of esters and amides is presented. In this new theory, the precise conformation of the intermediate hemi-orthoester or hemi-orthoamide controls the nature of the hydrolysis products. It is postulated that the breakdown of a conformer of a tetrahedral intermediate depends upon the orientation of the lone pair orbitals of the hetero-atoms. Specific cleavage of a carbon-oxygen or a carbon-nitrogen bond in any conformer is allowed only if the other two hetero-atoms (oxygen or nitrogen) each have an orbital oriented antiperiplanar to the leaving O-alkyl or N-alkyl group. Experimentally, the oxidation of acetals by ozone and the acid hydrolysis of a series of cyclic orthoesters demonstrates clearly that there is indeed a stereoelectronic control in the cleavage of hemiorthoesters. Similarly, a study of the basic hydrolysis of a variety of N,N-dialkylated imidate salts shows that the same stereoelectronic control is operating in the cleavage of hemiorthoamides.     

Infrared spectrum of cyclic ozone: a theoretical investigation

The infrared absorption spectrum of cyclic ozone is calculated by means of a new ab initio potential energy surface, the dipole moment function, and exact quantum mechanical dynamics calculations. Five different isotopomers are considered. The absorption line for excitation of the bending fundamental near 800 cm(-1) is by far the strongest band; all other bands are more than one order of magnitude less intense. This spectral pattern as well as the isotope shifts for the various isotopomers are important for identifying cyclic ozone. Several possibilities for accessing the ring minimum of cyclic ozone are also discussed on the basis of recent electronic structure calculations.     

Self-assembly of oligothiophene chromophores by m-calix[3]amide scaffold

m-Calix[3]amides carrying the bithiophene chromophore (BTC3A) and terthiophene chromophore (TTC3A) were synthesized by the cyclic trimerization of m-aminobenzoic acid esters for the purpose of the control and understanding of the self-assembly of oligothiophene chromophores. Polymers and model compounds were also prepared for comparison. From the (1)H NMR experiments, cyclic trimer BTC3A showed the syn/anti equilibrium in solution, and the syn/anti conformer ratio (76/24 in CDCl(3)) was influenced by the solvent character. Namely, the population of the syn conformer was lowest (70%) in THF-d(8) and was highest (86%) in CDCl(3)/CD(3)OD (1/1 in volume). On the other hand, the population of the syn conformer of cyclic trimer TTC3A was high (84%) even in CDCl(3). In a CHCl(3) solution of cyclic trimer BTC3A, the absorption maximum (342 nm) blue-shifted and the emission maximum (448 nm) red-shifted compared with those of polymer BTPA and model compound BTM. The solvent character also had an impact on the optical properties of cyclic trimer BTC3A. The red-shifted emission maximum (481 nm) of cyclic trimer BTC3A in CH(3)OH indicated the interaction between three bithiophene chromophores. The emission maxima of cyclic trimer TTC3A (486 nm) demonstrated a small red-shift from model compound TTM (477 nm), and no solvent dependency was observed, unlike cyclic trimer BTC3A.     

Conformation and Biological Activity of Cyclic Peptides

Cyclic peptides containing biologically active hormone sequences are suitable models for studying conformation-activity relationships. In such models the usual flexibility of peptide chains is reduced by their cyclic arrangement. However, conformational analysis of such systems by experimental means is possible only if a single conformer predominates at equilibrium, and criteria for this are put forward. NMR spectroscopic methods, including many recent advances, are discussed in relation to their ability to contribute to peptide conformational analysis.     

Gradient and mc scf calculations of the conformers and the formation of primary ethylene ozonide

The confonners of primary ethylene ozonide have been studied by ab initio gradient and MC SCF calculations. At the MC SCF level they are more spread in energy than in SCF calculations. The planar conformer, carbon-carbon half chair and the oxygen envelope are much higher m energy than the other conformers. The MC SCF activation energy for cyclo-addition of ozone and ethylene is 91–99 $\text{kJ}\text{mole}$.     

Transition metal complexes of cyclic and open ozone and thiozone

Cyclic ozone (O3) has not been isolated so far, despite its computed kinetic persistence. Possibilities of "trapping" this molecule (or the valence-isoelectronic cyclic thiozone, S3) in transition metal complexes are investigated in this paper. Candidates were constructed, first using the 18-electron rule as a guide and then optimizing the structures with the DFT-B3LYP method. A variety of structures result: oxo-peroxo species, di-sigma- and pi-bonded open ozone complexes, some eta1 and eta2 cyclic ozone complexes, and a few bona fide eta3 cyclic O3 and S3 complexes. MLn fragments suitable for complex formation would need to contain very strong pi-acceptor ligands. Nitrosyl ligands were chosen to minimize an energy mismatch between the O3 donor orbitals and the MLn acceptor orbitals. On this basis, the existence of the complexes [S3W(NO)3]3+, [O3M(NO)3]3+ (M = Cr, Mo, W, Fe, Ru, Os), and [S3W(NO)2(CO)]2+ containing cyclic O3 and S3 is suggested. In another approach, facing up to the oxidizing power of O3, potential systems were built from late transition metals in high oxidation states, and also d0 early transition metal centers.     

Synthesis of a novel cis-proline-derived cyclic type VI beta-turn mimic via ring-closing metathesis

A cis-proline derived cyclic mimic of a type VI beta-turn is synthesized via a ring-closing metathesis reaction. The solution NMR conformational study indicates that the major conformer of the cyclic peptide adopts a type VIa beta-turn in CDCl(3) and a type VIb beta-turn in DMSO-d(6).     

Molecular mechanics of saturated organic halides: Part I. Monochlorides and non-geminal dichlorides

A molecular-mechanical hydrocarbon force field is extended to apply to saturated organic chlorides, including non-geminal dichlorides. Simultaneous computation of molecular geometries, conformer energies, barriers to internal rotation, and dipole moments, is provided for. Results are reported and discussed for 17 molecules, acyclic and cyclic, including crowded structures.     

Hydration profiles of aromatic amino acids: conformations and vibrations of L-phenylalanine-(H2O)n clusters

IR-UV double resonance spectroscopy and ab initio calculations were employed to investigate the structures and vibrations of the aromatic amino acid, L-phenylalanine-(H(2)O)(n) clusters formed in a supersonic free jet. Our results indicate that up to three water molecules are preferentially bound to both the carbonyl oxygen and the carboxyl hydrogen of L-phenylalanine (L-Phe) in a bridged hydrogen-bonded conformation. As the number of water molecules is increased, the bridge becomes longer. Two isomers are found for L-Phe-(H(2)O)(1), and both of them form a cyclic hydrogen-bond between the carboxyl group and the water molecule. In L-Phe-(H(2)O)(2), only one isomer was identified, in which two water molecules form extended cyclic hydrogen bonds with the carboxyl group. In the calculated structure of L-Phe-(H(2)O)(3) the bridge of water molecules becomes larger and exhibits an extended hydrogen-bond to the pi-system. Finally, in isolated L-Phe, the D conformer was found to be the most stable conformer by the experiment and by the ab initio calculation.     

Conformation and spectroscopy study of cycloheptoxy radical

Alkoxy radicals are important intermediates in the formation of tropospheric ozone. The spectroscopic identification and characterization of these species are important for understanding their chemistry in the atmosphere. In this work, we report the observation of the laser induced fluorescence (LIF) excitation spectrum of cycloheptoxy radical. The spectrum was assigned preliminary to the lowest energy twist-chair conformer (TC-i) of cycloheptoxy. The whole picture of the interconversions at ground state between different conformers of cycloheptoxy radicals was described by density functional theory calculations. The results revealed that despite the ring strain, the seven-membered ring alkoxy radical could exist in the supersonic jet-cooled condition. The decomposition and the low energy barrier pseudorotation between twist-chair conformers might be the reason of the much quieter spectrum of cycloheptoxy compared with the LIF spectrum of cyclohexoxy.     

Calix[3]amides—bowl-shaped cyclic trimers toward building block for molecular recognition: self-complementary dimeric structure in the crystal

Bowl-shaped cyclic trimers of aromatic amides were simply synthesized in high yield by condensation reaction of meta-substituted 3-(alkylamino)benzoic acid using dichlorotriphenylphosphorane. The cyclic amides exist in syn conformation, which has a small chiral cavity, and a pair of each enantiomeric conformer formed a dimeric structure in the crystal.     

Theoretical prediction on the thermal stability of cyclic ozone and strong oxygen tunneling

Dual-level dynamics calculation with variational transition state theory including multidimensional tunneling has been performed on the isomerization reaction of cyclic ozone → normal (open) ozone, which was believed to be the stability-determining reaction of the elusive cyclic ozone molecule under thermal condition. The high-level potential energy surface data were obtained from the calculation using the MRCISD+Q theory with the aug-cc-pVQZ basis set, while the low-level reaction path information was obtained using the hybrid density functional theory B3LYP with the cc-pVTZ basis set. The calculated results showed very significant tunneling effects below 300 K (a factor of ～200 at 300 K and over 10(7) at 200 K). Because of the strong tunneling effects and the potential energy surface crossing of the 1A(1) and 1A(2) states, the isomerization reactions were found to be significantly faster than previously believed. The half-life of the cyclic ozone was estimated only ～10 s at 200 K and ～70 s below 100 K, which might partly explain the unsuccessful attempts for its experimental identification. The kinetic isotope effects (KIEs) for various (18)O substitution reactions were also calculated as a function of temperature and were as high as 10 at very low temperature. Because of the large KIEs, the experimental identification of the cyclic (18)O(3) seems more promising.     

Molecular mechanics of organic halides: Part IV. Monobromides and non-geminal dibromides

A molecular-mechanical hydrocarbon force field is extended to apply to saturated organic bromides, including non-geminal dibromides. Simultaneous calculation of molecular geometries, dipole moments, conformer energies and barriers to internal rotation is provided for. Results are reported for 34 molecules, acyclic and cyclic, representing altogether 78 structural variants. Variability in bond lengths and dihedral angles, and the “repulsive gauche effect”, are touched on in the discussion.     

Interaction of alcohols with 2-fluoro- and 4-fluorophenylacetylenes: infrared-optical double resonance spectroscopic and computational investigation

Alcohol complexes of 4-fluorophenylacetylene and 2-fluorophenylacetylene were investigated using IR-UV double resonance spectroscopy. Methanol forms a cyclic complex with both the fluorophenylacetylenes incorporating C-H···O and O-H···π hydrogen bonds, the structure of which is similar to that of the corresponding water complex but different from that of a phenylacetylene-methanol complex. The anti conformer of ethanol also binds in a similar fashion to both the fluorophenylacetylenes. Additionally, the gauche conformer of ethanol binds to 2-fluorophenylacetylene in a distinctly different structural motif that incorporates C-H···F and O-H···π hydrogen bonds. The OH group of trifluoroethanol interacts primarily with the π electron density of the C≡C bond. The π electron density of the C≡C bond is the principal point of interaction between the alcohols and both the fluorophenylacetylenes. The present results are indicative of the fact that fluorine substitution on the phenyl ring is sufficient to eliminate the subtle hydrogen bonding behavior of phenylacetylene.     

Electronic structure and conformational analysis of P218: An antimalarial drug candidate

P218 is one of the very important and recent lead compounds for antimalarial research. The 3D structural and electronic details of P218 are not available. In this article, quantum chemical studies to understand the possible 3D structures of P218 are reported and compared with 3D structures from the active site cavities of hDHFR and PfDHFR. The neutral P218, can adopt open chain as well as cyclic arrangements. Under implicit solvent condition a zwitterionic‐cyclic conformer is found to be quite possible. Microsolvation studies using explicit water molecules indicate that one water molecule may bridge the two ends of zwitterionic‐cyclic P218. It was observed that the protonation occurs preferentially at N¹ position of the 2,4‐diaminopyrimidine ring, with a proton affinity of 274.49 kcal/mol (implicit solvent phase) and 236.35 kcal/mol (gas phase). A dimer of P218 may be zwitterionic dimer, the dimer formation can release upto ～28.60 kcal/mol (implicit solvent phase).     

Potential polymorphs of aspirin

Aspirin is only found experimentally in one crystal structure. In this article, the method of Karfunkel and Gdanitz is used to predict potential polymorphs of aspirin. The known structure, containing a nonplanar conformer is found, along with a number of other low energy structures, many of which are based on a planar conformer. Semiempirical and ab initio calculations show that the planar conformer is less stable than the experimentally known one. Force field calculations suggest that the planar conformer is more stable. The lattice energy of the experimentally known crystal structure is 1.4 kcal/mol lower than any of the potential crystal structures, even though there are a number of structures with lower total (lattice+intramolecular) energies. Conformational maps indicate that another stable conformation occurs within a few kilocalories per mole of the known structure. Polymorphs are predicted for this conformer, but it is found to pack poorly. It is proposed that routes to producing polymorphs of aspirin might be found if consideration is given to promoting the stability of the planar conformer with appropriate solvents or additives. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 262–273, 1999     

Conservative change to the phosphate moiety of cyclic diguanylic monophosphate remarkably affects its polymorphism and ability to bind DGC, PDE, and PilZ proteins

The cyclic dinucleotide c-di-GMP is a master regulator of bacterial virulence and biofilm formation. The activations of c-di-GMP metabolism proteins, diguanylate cyclases (DGCs) and phosophodiesterases (PDEs), usually lead to diametrically opposite phenotypes in bacteria. Analogues of c-di-GMP, which can selectively modulate the activities of c-di-GMP processing proteins, will be useful chemical tools for studying and altering bacterial behavior. Herein we report that a conservative modification of one of the phosphate groups in c-di-GMP with a bridging sulfur in the phosphodiester linkage affords an analogue called endo-S-c-di-GMP. Computational, NMR (including DOSY), and CD experiments all reveal that, unlike c-di-GMP, endo-S-c-di-GMP does not readily form higher aggregates. The lower propensity of endo-S-c-di-GMP to form aggregates (as compared to that of c-di-GMP) is probably due to a higher activation barrier to convert from the "open" conformer (where the two guanines are on opposite faces) to the "closed" conformer (where the two guanines are on the same face). Consequently, endo-S-c-di-GMP has selectivity for proteins that bind monomeric but not dimeric c-di-GMP, which form from the "closed" conformer. For example, endo-S-c-di-GMP can inhibit the hydrolysis of c-di-GMP by RocR (a PDE enzyme that binds monomeric c-di-GMP) but did not bind to Alg44 (a PilZ protein) or regulate WspR (a DGC enzyme that has been shown to bind to dimeric c-di-GMP). This work demonstrates that selective binding to different classes of c-di-GMP binding proteins could be achieved by altering analogue conformer populations (conformational steering). We provide important design principles for the preparation of selective PDE inhibitors and reveal the role played by the c-di-GMP backbone in c-di-GMP polymorphism and binding to processing proteins.     

Torsional flexing: Conformational searching of cyclic molecules in biased internal coordinate space

A new stochastic (Monte Carlo) procedure, termed torsional flexing, has been devised for searching the conformational space of cyclic molecules. Torsional flexing causes a local, torsion angle-biased, distortion of a ring bond in a cyclic molecule. Because torsional flexing does not cause large atomic movements, even when it is applied to several bonds simultaneously, subsequent energy minimization generally proceeds rapidly. Nevertheless, the torsional flexing method is prone to generate structures that cross energy barriers so that the structure resulting after energy minimization is frequently a different conformer of the cyclic molecule. Conformational searches on cycloheptadecane, oxobrefeldin A, cyclopenta-L -alanine, and rifamycin SV based upon torsional flexing indicated that torsional flexing is among the best methods yet devised for searching the conformational space of flexible cyclic molecules. © 1993 John Wiley & Sons, Inc.     

Brønsted Acid versus Phase-Transfer Catalysis in the Enantioselective Transannular Aminohalogenation of Enesultams

We have studied the enantioselective transannular aminohalogenation reaction of unsaturated medium-sized cyclic benzosulfonamides by using both chiral Brønsted acid and phase-transfer catalysis. Under optimized conditions, a variety of bicyclic adducts can be obtained with good yields and high enantioselectivities. The mechanism of the reaction was also studied by using computational tools; we observed that the reaction involves the participation of a conformer of the nine-membered cyclic substrate with planar chirality in which the stereochemical outcome is controlled by the relative reactivity of the two pseudorotational enantiomers when interacting with the chiral catalyst.