On the si-n-bond - XLV1 : 2-aza-allenium cations: Synthesis,molecular structure and electrophilic ring closure to 1h-isoindoles

A new synthesis of 2-aza-allenium salts is described starting from N-trimethylsllylimines of aromatic ketones. Molecular structures and charge distributions of the linear allenoid and the angular allylic forms of monosubstituted 2-aza-allenium cations are calculated by the semiempirical MINDO/3 method. The u.v. spectra of tetraaryl-2-aza-allenium cations have been measured and interpreted by theoretical transition energies obtained from modified PPP investigations. The theoretical heats of formation suggest the linear allenoid structure of all of these cations to be favoured. Low energy differences between the linear and the angular geometries as well as the high positive charge at the carbon atoms of the C-N-C systems may explain the eleetrophilic ring closure to 1H-iaoindoles found experimentally.     

Annular tautomerism: experimental observations and quantum mechanics calculations

The use of MP2 level quantum mechanical (QM) calculations on isolated heteroaromatic ring systems for the prediction of the tautomeric propensities of whole molecules in a crystalline environment was examined. A Polarisable Continuum Model was used in the calculations to account for environment effects on the tautomeric relative stabilities. The calculated relative energies of tautomers were compared to relative abundances within the Cambridge Structural Database (CSD) and the Protein Data Bank (PDB). The work was focussed on 84 annular tautomeric forms of 34 common ring systems. Good agreement was found between the calculations and the experimental data even if the quantity of these data was limited in many cases. The QM results were compared to those produced by much faster semiempirical calculations. In a search for other sources of the useful experimental data, the relative numbers of known compounds in which prototropic positions were often substituted by heavy atoms were also analysed. A scheme which groups all annular tautomeric transformations into 10 classes was developed. The scheme was designed to encompass a comprehensive set of known and theoretically possible tautomeric ring systems generated as part of a previous study. General trends across analogous ring systems were detected as a result. The calculations and statistics collected on crystallographic data as well as the general trends observed should be useful for the better modelling of annular tautomerism in the applications such as computer-aided drug design, small molecule crystal structure prediction, the naming of compounds and the interpretation of protein—small molecule crystal structures.     

Stability of the normal, zwitterionic neutral and anionic forms of aspartic acid in gas phase and aqueous media

Aspartic acid has a place of special importance among amino acids in view of its property to racemize from the - to the -form in living and nonliving systems which can be used to determine age. Molecular geometries of two isomeric normal neutral forms (called A and B forms), isomeric zwitterionic neutral forms (called A(Z) and B(Z) forms) and anions of these forms of aspartic acid were optimized at the RHF/6-31+G^* level. The geometries of hydrogen bonded complexes of each of the above species with one, two and three water molecules were also optimized at the same level. All these systems were solvated in bulk water using the polarized continuum model (PCM) of the self-consistent reaction field (SCRF) theory at the RHF/6-31+G^* level using the gas phase optimized geometries. It is found that in gas phase, the normal neutral A and B forms of aspartic acid would coexist while the zwitterionic A(Z) and B(Z) forms of the same would be absent. On the other hand, in bulk aqueous media, the normal neutral A and B forms of aspartic acid would not occur while the zwitterionic A(Z) and B(Z) forms would be present. Further, the abundance of the A(Z) form would be much more than that of the B(Z) form in bulk water. If the solution pH is adjusted appropriately so that a monoanion is formed, the anion of aspartic acid obtained from the neutral zwitterionic form by deprotonating O₈ would occur dominantly.     

X-ray crystal structure analysis and atomic charges of color former and developer: 5. Colored formers

The spirocarbon C6 of colorless forms of a fluoran compound is the base of the disengagement from the bond C(sp³)–O by the accessibility of the electrophilic H⁺, the phthalide ring is cleaved and this ring becomes a benzene ring D and a carboxyl group as colored forms. The crystal and molecular structures of colored forms 2-anilino-3-methyl-6-diethylamino-9-(o-carboxyphenyl) xanthene C₃₁H₂₉N₂O₃⁺·Cl⁻ (1) and 2-methyl-3-anilino-7-dibutylamino-9-(o-carboxyphenyl) xanthene C₃₅H₃₇N₂O₃⁺·Cl⁻ (2) complexes were determined by single-crystal X-ray diffraction analysis. The xanthene ring skeletons of colored forms 1 and 2 have planar geometries, and the ring junctions between the xanthene ring and the benzene ring D make a small angle compared to the colorless forms which are almost at right angles to the xanthene ring skeletons. 1 and 2 are just different from the ethyl and butyl groups in two side chains R¹ and R², but the rigid body and internal motions in molecules differ at R¹ and R⁵ (the ring F). The charges of the root atom N1 of the two side chains are increased by π-electron densities, those from N1 to C6 atoms show distinct odd alternant system, and two oxygens (O2 and O3) of the carboxyl group are decreased. The group charges of N1 of colored forms are positive, while those of the colorless forms are negative. Colored forms make networks of X–HY contacts with an anion Cl⁻ and the anion in the nucleus of network. It is explained here that delicate positive charges of atoms N2 and O2 cause ClH(N2)–N2 and ClH(O2)–O2 contacts.     

桥环三元环苯的结构和芳香性研究

用Gaussian 03程序,采用密度泛函理论方法,对桥环三元环苯的结构和芳香性进行研究,优化得到了其稳定平衡构型,讨论了结构,通过核独立化学位移（NICS）和分子轨道（MO）分析,确定了桥环三元环苯的芳香性与键的定域之间是没有联系的,分子中的各个环的环电流大小是由取代基所决定的．     

Fluorescence quenching of dyes by tryptophan: interactions at atomic detail from combination of experiment and computer simulation

Fluorescence spectroscopy and molecular dynamics (MD) simulation are combined to characterize the interaction of two organic fluorescent dyes, rhodamine 6G (R6G) and an oxazine derivative (MR121), with the amino acid tryptophan in aqueous solution. Steady-state and time-resolved fluorescence quenching experiments reveal the formation of essentially nonfluorescent ground-state dye/Trp complexes. The MD simulations are used to elucidate the molecular interaction geometries involved. The MD-derived probability distribution of the distance r between the centers of geometry of the dye and quencher ring systems, P(r), extends to higher distances for R6G than for MR121 due to population in the R6G/Trp system of fluorescent interaction geometries between Trp and the phenyl ring and ester group of the dye. The consequence of this is the experimental finding that under the conditions used in the simulations about 25% of the R6G dye is fluorescent in comparison with 10% of the MR121. Combining the above findings allows determination of the "quenching distance", r, above which no quenching occurs. r is found to be very similar (approximately 5.5 A) for both dye/Trp systems, corresponding to close to van der Waals contact. Both experimental dynamic Stern-Volmer analysis and the MD trajectories demonstrate that the main determinant of the fluorescence intensity is static quenching. The approach presented is likely to be useful in the structural interpretation of data obtained from fluorescent conjugates commonly used for monitoring the binding and dynamics of biomolecular systems.     

Design,stereoselective synthesis and computational calculations of novel hybrid compounds via Pauson-Khand reactions

A series of novel chiral hybrid compounds between benzofuran and bicyclic cyclopentenone and also benzothiophene and bicyclic cyclopentenone have been designed and synthesized. Chiral enynes derived from enantiomerically enriched homoallyl and homopropargyl alcohols were converted into bicyclic cyclopentenone structures by intramolecular Pauson-Khand reactions. This strategy provides a facile access to various bicyclic cyclopentenones substituted with benzofuran or benzothiophene ring systems in good yields. In addition to the experimental work, the ground state geometries of the hybrid compounds were optimized using Density Functional Theory applications at the B3LYP/6-31G(d,p) level in order to obtain information about the 3D geometries and electronic structure.     

Thermodynamic stability of 2,4,6-tris(nitromethyl)-1,3,5-triazine: an experimental and theoretical study

The molecular geometries and electronic structures of 2,4,6-tris(nitromethyl)-1,3,5-triazine isomers were investigated by the density functional method DFT/B3LYP/6-311++G** to elucidate the structural factors responsible for the stability of these systems. It was shown that a characteristic feature of the nitromethyl tautomer (1) of 2,4,6-tris (nitromethyl)-1,3,5-triazine consists in nonvalence interactions between an oxygen atom of nitro group and a carbon atom of triazine ring, which are probably due to Coulomb attraction between them. The tautomer with the 2,4,6-tris (nitromethylene)-hexahyrdo-1,3,5-triazine structure (2) is stabilized trough direct polar conjugation between the amino and nitro groups at the double bond. Structural strain of the molecule with the 2,4,6-tris(aci-nitromethyl)-1,3,5-triazine structure (3) is the reason for its thermodynamic instability. X-ray data indicate that the compound under study exists in the triazine tautomeric form 1 and the distances between oxygen atoms of nitro group and carbon atom of the triazine ring are shortened. NMR data suggest the existence of triazine in the nitromethyl form 1 in acetonitrile and acetone and a tautomeric equilibrium between the nitromethyl and nitromethylene forms in a more polar solvent (DMSO). The results obtained suggest a Coulomb-type stabilization of the 2,4,6-tris(nitromethyl)-1,3,5-triazine molecule in the gas phase, in the crystal, and in nonpolar solvents.     

Synthesis, structures, and strain energies of dispirophosphiranes. Comparisons with dispirocyclopropanes

Six novel dispirophosphirane complexes have been synthesized from the reaction of bicycloalkylidenes with the electrophilic phosphinidene complex PhPW(CO)(5). They contain a central phosphirane ring, which is spirofused on one side to a cyclopropane or cyclobutane ring and on the other side with a three-, four-, five-, or six-membered ring. Their crystal structures and MP2/6-31G-computed geometries for simplified parent systems suggest that spirofusion with small rings results in a tightening of the central three-membered phosphaheterocycle, while spirofusion with larger rings results in a relaxation of the phosphirane geometry. Similar theoretical predictions are made for the corresponding annulated hydrocarbons. Strain energies for both the hydrocarbon and phosphorus series of structures have been calculated at G3(MP2). Whereas the [3]triangulane hydrocarbon and phospha[3]triangulane have a significant excess strain of 8.1 and 5.2 kcal/mol per spiroatom, respectively, the excess strain for systems spirofused with larger rings are negligible for the hydrocarbons and even negative for the phosphorus-containing species because of hyperconjugative stabilization.     

The structure and properties of flavins: Molecular orbital study based on totally optimized geometries. I. Molecular geometry investigations

Molecular orbital calculations (MINDO /3) using energy minimized molecular geometries were performed on oxidized and reduced lumiflavin and related methylated isoalloxazines, including cationic and anionic species. Close agreement with experimental geometry, photoelectron spectra, and NMR data supports the importance of optimized geometries for these molecular systems and provides the basis for interpretation of chemical and biological properties. Oxidized forms are shown to be most stable in the planar configuration but also highly flexible about the N(5)—N(10) axis; only 1 kcal/mol is required for a 10° bend. N(10) is generally out of the plane slightly; also, C(9)-methyl substitution introduces nonplanarity. The unsubstituted isoalloxazine is computed to be 0.76 kcal/mol (ΔH) less stable than its isomer, alloxazine. Calculations were also performed on enol as well as quinone-methide tautomeric forms. Reduced flavin geometry depends on methyl substitution pattern: N(10) substituted forms are bent with typical fold angles around 155°, whereas the unsubstituted reduced form is planar. Both oxidized and reduced forms are also flexible. Proton affinities were calculated for protonation and deprotonation of oxidized and reduced forms. Protonation of oxidized forms is favored at N(1) by 10–12 kcal/mol and produces somewhat nonplanar isoalloxazinium ions. In addition, ΔH for the two-electron reduction of lumiflavin is estimated to be ?19.7 kcal/mol. In this paper investigations of geometric aspects are presented along with introductory and background material. Orbital structure and electron distribution studies are presented in paper II.     

Structural Analysis of Isomeric Europium(III) Chelates of NB-DOTMA

Water exchange in lanthanide(III) chelates is a key parameter in developing more effective MRI contrast agents. Our own efforts to optimize water exchange have focused on isolating single coordination geometries of LnDOTA-type chelates (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate.) This isolation may be achieved by appropriately substituting the ligand framework to freeze-out the conformational exchange processes that interconvert coordination geometries. When a single nitrobenzyl substituent is used to "lock" the conformation of the macrocyclic ring, two regioisomeric chelates may be produced; the substituent may be alternatively located on the corner or the side of the ring. Here, we unambiguously demonstrate this regioisomerism by examining the COSY spectra of some conformationally locked Eu(3+) chelates. This exercise also demonstrated that diastereoisomeric chelates arising from racemization of chiral centers during the ligand synthesis, recently discounted as the origin of multiple isomeric chelates, can be produced and isolated. Furthermore, these COSY data revealed several through space NOE correlations that afford a great deal of information about the conformation of the nitrobenzyl substituent. In those isomers in which the substituent is located on the corner of the ring, the nitrobenzyl group is oriented approximately perpendicular to the plane of the macrocycle pointing upward and away from the chelate. In contrast, when the substituent is located on the side of the ring, the nitrobenzyl group is oriented approximately in plane with the macrocycle, pointing along the side of the chelate. Because the main purpose of the nitro group is to facilitate chemical modification and conjugation to biologically relevant molecules, these differences may have important consequences. Specifically, it seems likely that the same chelate may interact very differently with biological systems and molecules depending upon the regioisomer and therefore the orientation of the chelate relative to the biomolecule.     

Hydrogen bonded complexes of oxazole family: electronic structure,stability, and reactivity aspects

Structural Chemistry - In the present study, five-membered heterocyclic ring systems containing oxygen with one, two, three, and four nitrogen atoms in the ring along with their isomeric forms and...     

Density functional theory and ab initio studies of geometry, electronic structure and vibrational spectra of novel benzothiazole and benzotriazole herbicides

The ground-state geometries, electronic structures and vibrational wavenumbers of S-1,3-benzothiazolyl-4-bromobenzenecarbothioate and S-(5,7-dimethyl-3H-4lambda-5-[1,2,4]triazolo[1,5-a]pyridinyl)4-chlorobenzenecarbothioate were studied by DFT-B3LYP, BLYP and ab initio RHF method with different basis sets. The comparison was performed for optimized geometries, thermodynamic parameters and electronic structures at different levels of theory. Because of the larger repulsion effect in triazole ring, the vibrational wavenumbers of skeleton vibration of triazole ring are significantly lower than that of thiazole ring.     

Intramolecular Resonance-assisted Hydrogen Bonds in N-Salicylidene-anilines

In the crystal structures of N-salicylidene-anilines, the ortho-OH group with the central N atom forms a planar six-membered ring through intramolecular hydrogen bonds (Fig. 1). The pseudo-aromatic ring is coplanar with its attached phenyl ring. The resonance strengthens the H-bond through proton transfer between the O and N atoms (Fig.1,Ⅰ←→Ⅱ): dco and dcc become shorter and dCN longer significantly. The d1～d6 are also changed regularly. According to the geometries obtained from X-ray analysis and retrieved from the Cambridge Structural Database (CSD, version 5.21), we believe that the main resonance, at least in solid state, is the molecular keto form (Ⅱ, Fig. 1) instead of the zwitterionic one (Ⅲ, Fig.1).     

Probing the structural and electronic effects to stabilize nonplanar forms of thioamide derivatives: A computational study

Density functional calculations have been performed to examine the stability of nonplanar conformations of thioamide derivatives. Electrostatic, orbital, and ring strain effects were invoked to stabilize the nonplanar conformations of thioamide systems 2 – 7 . Electrostatic interactions helped to achieve the twisted forms of thioamide derivatives; however, pyramidal forms predicted to be the global minimum. Negative hyperconjugative type interactions enhanced the stability of the twisted form 4b when compared with the planar form 4a . The influence of ring strain effect to achieve the twisted form of thioamide was observed with azirine ring. The predictions made with B3LYP/cc‐pVDZ+ level of theory was found to be in good agreement with more accurate CBS‐QB3 method. The solvent calculations performed with polarized continuum solvation model suggest that the relative stabilities of the nonplanar forms of thioamide derivatives are in general similar to the gas phase results. The importance of hydrogen bonding interactions between the solvent molecules and thioamide derivatives was observed toward the enhanced stability of twisted forms using a combination of explicit solvent molecules and continuum model. The natural bond orbital analysis confirmed the participation of n_N → π*_C?S delocalizations in the planar forms and corroborated the earlier reports on larger delocalizations in thioamide systems. Furthermore, the influence of electrostatic and ring strain effects on the amide, natural amides, and selenoamide has also been studied. © 2011 Wiley Periodicals, Inc. J Comput Chem 2011     

Theoretical study of geometry and nucleophilicity of the exocyclic methylene in five-membered ring cyclic ketene acetals,neutral and protonated,containing pnictogen and chalcogen heteroatoms

A series of neutral and protonated five-membered ring cyclic ketene acetals have been examined computationally for any trends in nucleophilicity in the exocyclic methylene and for their ground state geometries. A total of 58 different species were examined, 29 neutral molecules and the corresponding 29 protonated species. The heteroatoms that were used in the heterocyclic ring were a combination of nitrogen, phosphorus, and arsenic from the pnictogen family and oxygen, sulfur, and selenium from the chalcogen family. All geometries were initially optimized at using density functional theory and all stationary points were confirmed to be either minima or transition states through vibrational analysis. All the geometries were consequentially optimized using Møller–Plesset second order perturbation theory with a polarized triple zeta basis set. The main focus of the study was the nucleophilicity of the exocyclic methylene carbon atom and its dependence on heteroatom substitution. As probes for nucleophilicity, the proton affinities of the neutral species, the bond lengths of the exocyclic double bond, and atomic charges were used. The study also resulted in some interesting molecular geometries.     

Ab initio structural investigation of methyl and ethyl carbamate, and carbamyl choline

The molecular structures of four conformations of methylcarbamate, three forms of ethylcarbamate, four forms of ethylacetate, and of the trans-form of carbamylcholine, were determined by ab initio gradient geometry refinement on the 4-21G level, and the results are compared with the geometries of homologous systems. Significant changes in bond distances and angles are observed with torsional changes, but, barring long-range non-bonded interactions, they are to a large extent localized in that part of the system which is directly involved with the torsional transition; i.e., through-bond effects in a bond distance chain begin to be insignificant after a sequence of three bonds.     

The Intramolecular Interaction of Thiophene and Furan with Aromatic and Fluoroaromatic Systems in Some [3.3]Meta(heterocyclo)paracyclophanes: A Combined Computational and NMR Spectroscopic Study

Four thiophene‐ and furan‐containing [3.3]meta(heterocyclo)paracyclophanes were designed and synthesized to study the intramolecular interaction between standard heteroaromatic rings and tetra‐H‐ or tetra‐F‐substituted benzenes. A complete conformational analysis, carried out by DFT calculations and variable‐temperature NMR techniques, showed that, despite their structural similarity, these adducts have different conformational preferences and undergo different types of isomerizations depending on the nature of the heterocycle. The thiophene‐derived adducts adopted a parallel stacked arrangement of the aromatic systems in the ground‐state conformations. Their isomerization pathways involved a thiophene ring‐flip process passing through an edge‐to‐face arranged transition state in which the heterocycle is perpendicular to the benzene platform and its sulfur atom points toward the center of that ring. The threshold energy barrier to the ring‐flip process was higher by 10 kJ mol^?1 in the case of the adduct featuring the perfluorinated benzene. This difference was rationalized by assuming that the ground‐state conformations of the H‐ and F‐substituted compounds have different stability. On the contrary, the furan‐derived adducts were shown by calculations and NMR spectroscopy to adopt, in their ground‐state conformations, a perpendicular edge‐to‐face disposition of the rings with the oxygen atom pointing toward the benzene platform. The adoption of this arrangement was confirmed by X‐ray crystallography. In the case of these compounds, the isomerization process involved distortion of the CH₂SCH₂ bridges connecting the aromatic systems and the adoption of transition‐state geometries for which the rings were arranged in a parallel‐stacked orientation. Once again a very nice agreement was observed between the predicted and the experimentally determined geometries and pathways. In the case of the furan‐containing compounds, the threshold barriers were found to be much lower in energy that those observed for the thiophene derivatives. Remarkably, they were virtually independent of the presence of fluorine atoms on the platform benzene ring.     

An ab initio theoretical study of electronic structure and properties of 2'-deoxyguanosine in gas phase and aqueous media

Molecular geometries of two structural forms of 2'-deoxyguanosine (keto-N9R and keto-N7R, R = the sugar moiety) considering both the C2'-endo and C3'-endo conformations of the sugar ring and those of the complexes of these species with two water molecules each were optimized employing the ab initio RHF procedure. A mixed basis set consisting of the 6-311+G* basis set for the nitrogen atom of the amino group and the 4-31G basis set for all the other atoms was used. The RHF calculations were followed by correlation correction of the total energy at the MP2 level. Both the structural forms of 2'-deoxyguanosine were solvated using the polarized continuum model (PCM) of the self-consistent reaction field (SCRF) theory and the corresponding RHF optimized geometries at the RHF and MP2 levels. Geometry optimization was also performed in aqueous media using the Onsager model at the RHF level using the above-mentioned mixed basis set, and subsequently, using the reoptimized geometries, single-point MP2 calculations were performed. It is found that both the keto-N9R and keto-N7R forms of 2'-deoxyguanosine as well as their complexes with two water molecules each would occur, particularly at the water-air interface. Though the normal Watson-Crick-type base pairing would not be possible with the keto-N7R form of 2'-deoxyguanosine(G*), two other (G*-C and G*-T) base pairing schemes may occur with this form of the nucleoside, which may cause mutation. The present calculated geometry of the keto-N9R form of the anti-conformation of 2'-deoxyguanosine including the dihedral angle chi(CN) agree satisfactorily with the available crystallographic results. The present results also agree satisfactorily with those obtained by other authors earlier for the keto-N9R form of 2'-deoxyguanosine using B3LYP and MP2 methods employing the 6-31G* basis set. Using transition state calculations, it is shown that tautomerism of guanine and other similar molecules where the tautomers would coexist would be facilitated by the occurrence of the H(+) and OH(-) fragments of water molecules. Further, this coexistence of the two tautomers appears to make the C8 carbon atom located between the N7 and N9 nitrogen atoms susceptible to attack by the OH(-) group. Thus, an explanation is obtained for the efficient formation of the reaction product 8-hydroxy-2'-deoxyguanosine, which serves as a biomarker for oxidative damage to DNA in biological systems.