Exploring the Optoelectronic Properties of D-A and A-D-A 2,2'-bi[3,2-b]thienothiophene Derivatives.

The synthesis of some novel donor-acceptor and acceptor-donor-acceptor systems containing a 2,2'-bi[3,2-b]thienothiophene donor block and various electron-accepting units is described alongside their photophysical properties studied using electrochemistry, optical spectroscopy and theoretical calculations. The obtained results show that the energy levels can be modulated by changing the strength of the acceptor unit. Among the three investigated end-groups, 1,1-dicyanomethylene-3-indanone exhibited the largest bathochromic shift and the lowest band gap suggesting the strongest electron-withdrawing character. Moreover, the emissive properties of the investigated systems vary greatly with the nature of the terminal group and are generally lower compared to their precursor aldehyde derivatives.

A three-armed cryptand with triazine and pyridine units: synthesis, structure and complexation with polycyclic aromatic compounds.

The aromatic nucleophilic substitution reaction based synthesis of a three-armed cryptand displaying 2,4,6-triphenyl-1,3,5-triazine units as caps and pyridine rings in the bridges, along with NMR, MS and molecular modelling-based structural analysis of this compound are reported. Appropriate NMR and molecular modelling investigations proved the formation of 1:1 host-guest assemblies between the investigated cryptand and some polynuclear aromatic hydrocarbons or their derivatives.

Modulating short tryptophan- and arginine-rich peptides activity by substitution with histidine.

BACKGROUND: High antimicrobial efficacy of short tryptophan-and arginine-rich peptides makes them good candidates in the fight against pathogens. Substitution of tryptophan and arginine by histidine could be used to modulate the peptides efficacy by optimizing their structures. METHODS: The peptide (RRWWRWWRR), reported to showed good antimicrobial efficacy, was used as template, seven new analogs being designed substituting tryptophan or arginine with histidine. The peptides' efficacy was tested against E. coli, B. subtilis and S. aureus. The cytotoxicity and hemolytic effect were evaluated and the therapeutic index was inferred for each peptide. Atomic force microscopy and molecular simulation were used to analyze the effects of peptides on bacterial membrane. RESULTS: The substitution of tryptophan by histidine proved to strongly modulate the antimicrobial activity, mainly by changing the peptide-to-membrane binding energy. The substitution of arginine has low effect on the antimicrobial efficacy. The presence of histidine residue reduced the cytotoxic and hemolytic activity of the peptides in some cases maintaining the same efficacy against bacteria. The peptides' antimicrobial activity was correlated to the 3D-hydrophobic moment and to a simple structure-based packing parameter. CONCLUSION: The results show that some of these peptides have the potential to become good candidates to fight against bacteria. The substitution by histidine proved to fine tune the therapeutic index allowing the optimization of the peptide structure mainly by changing its binding energy and 3D-hydrophobic moment. GENERAL SIGNIFICANCE: The short tryptophan reach peptides therapeutic index can be maximized using the histidine substitution to optimize their structure.

A Study of Intramolecular Hydrogen Bonding in Levoglucosan Derivatives.

Organofluorine is a weak hydrogen-bond (HB) acceptor. Bernet et al. have demonstrated its capability to perturb OH···O intramolecular hydrogen bonds (IMHBs), using conformationally rigid carbohydrate scaffolds including levoglucosan derivatives. These investigations are supplemented here by experimental and theoretical studies involving six new levoglucosan derivatives, and complement the findings of Bernet et al. However, it is shown that conformational analysis is instrumental in interpreting the experimental data, due to the occurrence of non-intramolecular hydrogen-bonded populations which, although minor, cannot be neglected and appears surprisingly significant. The DFT conformational analysis, together with the computation of NMR parameters (coupling constants and chemical shifts) and wavefunction analyses (AIM, NBO), provides a full picture. Thus, for all compounds, the most stabilized structures show the OH groups in a conformation allowing IMHB with O5 and O6, when possible. Furthermore, the combined approach points out the occurrence of various IMHBs and the effect of the chemical modulations on their features. Thus, two-center or three-center IMHB interactions are observed in these compounds, depending on the presence or absence of additional HB acceptors, such as methoxy or fluorine.

Influence of Alcohol ß-Fluorination on Hydrogen-Bond Acidity of Conformationally Flexible Substrates.

Rational modulations of molecular interactions are of significant importance in compound properties optimization. We have previously shown that fluorination of conformationally rigid cyclohexanols leads to attenuation of their hydrogen-bond (H-bond) donating capacity (designated by pKAHY ) when OH⋅⋅⋅F intramolecular hydrogen-bond (IMHB) interactions occur, as opposed to an increase in pKAHY due to the fluorine electronegativity. This work has now been extended to a wider range of aliphatic ß-fluorohydrins with increasing degrees of conformational flexibility. We show that the observed differences in pKAHY between closely related diastereomers can be fully rationalized by subtle variations in populations of conformers able to engage in OH⋅⋅⋅F IMHB, as well as by the strength of these IMHBs. We also show that the Kenny theoretical Vα (r) descriptor of H-bond acidity accurately reflects the observed variations and a calibration equation extended to fluorohydrins is proposed. This work clearly underlines the importance of the weak OH⋅⋅⋅F IMHB in the modulation of alcohol H-bond donating capacity.

Supramolecular anion recognition by ß-HCH.

The formation of highly ordered supramolecular architectures via cooperative C(aliphatic)-H·anion contacts between ß-HCH and various anions (Cl-, Br-, I- and HSO4-) was investigated by single crystal X-ray diffractometry, molecular modelling, ESI-MS and 1H-NMR titrations.

Indenopyrans - synthesis and photoluminescence properties.

New indeno[1,2-c]pyran-3-ones bearing different substituents at the pyran moiety were synthesized and their photophysical properties were investigated. In solution all compounds were found to be blue emitters and the trans isomers exhibited significantly higher fluorescence quantum yields (relative to 9,10-diphenylanthracene) as compared to the corresponding cis isomers. The solid-state fluorescence spectra revealed an important red shift of λmax due to intermolecular interactions in the lattice, along with an emission-band broadening, as compared to the solution fluorescence spectra.

α-Fluoro-o-cresols: The Key Role of Intramolecular Hydrogen Bonding in Conformational Preference and Hydrogen-Bond Acidity.

The conformational preferences of o-cresols driven by fluorination were thoroughly investigated from a theoretical point of view with quantum-chemical methods, and the results were compared to those recently reported for benzyl alcohols. The key conformers of both families exhibit a six-membered intramolecular hydrogen-bond (IMHB) interaction. A significant enhancement in the strength of the IMHB is observed in α-fluoro-o-cresols, owing to a simultaneous increase in the hydrogen bond (HB) basicity of the aliphatic fluorine and the HB acidity of the aromatic hydroxyl relative to that observed for o-fluorobenzyl alcohols, which are characterized by aromatic fluorine atoms and aliphatic hydroxyl groups. In the cases of the di- and trifluorinated derivatives, the occurrence of a three-centered HB is emphasized, and its features are discussed. The impact of these structural predilections on the HB properties of o-cresol was characterized from the estimation of the HB acidity parameter, pKAHY , weighted according to their conformational populations. We found that α-fluorination led to a decrease in the HB acidity of the hydroxyl group (in contrast with the o-fluorination of benzyl alcohols), whereas α,α-difluorination resulted in no significant variation in pKAHY . Finally, an increase in the HB acidity was predicted upon methyl perfluorination, which was confirmed experimentally. Theoretical descriptors based on atoms in molecules, noncovalent interactions, and natural bond orbital analyses allowed rationalization of the predicted trends and revealed a relationship with the strength of the established OH⋅⋅⋅F IMHB.

Intramolecular OH⋠⋠⋠Fluorine Hydrogen Bonding in Saturated, Acyclic Fluorohydrins: The γ-Fluoropropanol Motif.

Fluorination is commonly exercised in compound property optimization. However, the influence of fluorination on hydrogen-bond (HB) properties of adjacent functional groups, as well as the HB-accepting capacity of fluorine itself, is still not completely understood. Although the formation of OH⋅⋅⋅F intramolecular HBs (IMHBs) has been established for conformationally restricted fluorohydrins, such interaction in flexible compounds remained questionable. Herein is demonstrated for the first time-and in contrast to earlier reports-the occurrence of OH⋅⋅⋅F IMHBs in acyclic saturated γ-fluorohydrins, even for the parent 3-fluoropropan-1-ol. The relative stereochemistry is shown to have a crucial influence on the corresponding (h1) JOH⋅⋅⋅F values, as illustrated by syn- and anti-4-fluoropentan-2-ol (6.6 and 1.9 Hz). The magnitude of OH⋅⋅⋅F IMHBs and their strong dependence on the overall molecular conformational profile, fluorination motif, and alkyl substitution level, is rationalized by quantum chemical calculations. For a given alkyl chain, the "rule of shielding" applies to OH⋅⋅⋅F IMHB energies. Surprisingly, the predicted OH⋅⋅⋅F IMHB energies are only moderately weaker than these of the corresponding OH⋅⋅⋅OMe. These results provide new insights of the impact of fluorination of aliphatic alcohols, with attractive perspectives for rational drug design.

Influence of Fluorination on the Conformational Properties and Hydrogen-Bond Acidity of Benzyl Alcohol Derivatives.

The effect of fluorination on the conformational and hydrogen-bond (HB)-donating properties of a series of benzyl alcohols has been investigated experimentally by IR spectroscopy and theoretically with quantum chemical methods (ab initio (MP2) and DFT (MPWB1K)). It was found that o-fluorination generally resulted in an increase in the HB acidity of the hydroxyl group, whereas a decrease was observed upon o,o'-difluorination. Computational analysis showed that the conformational landscapes of the title compounds are strongly influenced by the presence of o-fluorine atoms. Intramolecular interaction descriptors based on AIM, NCI and NBO analyses reveal that, in addition to an intramolecular OH⋅⋅⋅F interaction, secondary CH⋅⋅⋅F and/or CH⋅⋅⋅O interactions also occur, contributing to the stabilisation of the various conformations, and influencing the overall HB properties of the alcohol group. The benzyl alcohol HB-donating capacity trends are properly described by an electrostatic potential based descriptor calculated at the MPWB1K/6-31+G(d,p) level of theory, provided solvation effects are taken into account for these flexible HB donors.

Selective host molecules obtained by dynamic adaptive chemistry.

Up till 20 years ago, in order to endow molecules with function there were two mainstream lines of thought. One was to rationally design the positioning of chemical functionalities within candidate molecules, followed by an iterative synthesis-optimization process. The second was the use of a "brutal force" approach of combinatorial chemistry coupled with advanced screening for function. Although both methods provided important results, "rational design" often resulted in time-consuming efforts of modeling and synthesis only to find that the candidate molecule was not performing the designed job. "Combinatorial chemistry" suffered from a fundamental limitation related to the focusing of the libraries employed, often using lead compounds that limit its scope. Dynamic constitutional chemistry has developed as a combination of the two approaches above. Through the rational use of reversible chemical bonds together with a large plethora of precursor libraries, one is now able to build functional structures, ranging from quite simple molecules up to large polymeric structures. Thus, by introduction of the dynamic component within the molecular recognition processes, a new perspective of deciphering the world of the molecular events has aroused together with a new field of chemistry. Since its birth dynamic constitutional chemistry has continuously gained attention, in particular due to its ability to easily create from scratch outstanding molecular structures as well as the addition of adaptive features. The fundamental concepts defining the dynamic constitutional chemistry have been continuously extended to currently place it at the intersection between the supramolecular chemistry and newly defined adaptive chemistry, a pivotal feature towards evolutive chemistry.

(3-Chloro-phen-yl){2-eth-oxy-5-[(Z)-hydroxy(phen-yl)methyl-idene]cyclo-penta-1,3-dien-1-yl}methanone.

The title compound, C(21)H(17)ClO(3), which crystallizes as one of two possible oxo/hy-droxy-fulvene prototropic tautomers, possesses a strong intra-molecular O-H⋯O hydrogen bond that closes a seven-membered ring. The dihedral angles between the central five-membered ring and two pendant rings are 55.05 (9) and 44.51 (10)°. The crystal packing is characterized by weak inter-molecular C-H⋯O inter-actions between an H atom of the oxymethyl-ene unit and the carbonyl group of an adjacent mol-ecule, resulting in formation of chains of mol-ecules along the a axis.

Reference molecules for nonlinear optics: a joint experimental and theoretical investigation.

Hyper-Rayleigh scattering (HRS) experiments and quantum chemical calculations are combined to investigate the second-order nonlinear optical responses of a series of reference molecules, namely, carbon tetrachloride, chloroform, trichloroacetonitrile, acetonitrile, and dichloromethane. The multipolar decomposition of the first hyperpolarizability tensor through the use of the spherical harmonics formalism is employed to highlight the impact of the symmetry of the molecular scatterers on their nonlinear optical responses. It is demonstrated that HRS is a technique of choice to probe the molecular symmetry of the compounds. Coupled-cluster calculations performed at the coupled-cluster level with singles, doubles, and perturbative triples in combination with highly extended basis sets and including environment effects by using the polarizable continuum model qualitatively reproduce the molecular first hyperpolarizabilities and depolarization ratios of the molecular scatterers.

Effects of the nature and length of the π-conjugated bridge on the second-order nonlinear optical responses of push-pull molecules including 4,5-dicyanoimidazole and their protonated forms.

Theoretical and experimental methods of characterization have been employed to investigate a series of six push-pull molecules containing a 4,5-dicyanoimidazole acceptor (A) unit, a N,N-dimethylamino donor (D) group, and systematically enlarged π-conjugated linkers (π) with the view of assessing their first hyperpolarizabilities (ß) as well as their variations upon protonation. The results demonstrated that protonation occurred at the N,N-dimethylamino function, which led to disruption of the electronic charge-transfer delocalization: the A-π-D pattern of the neutral species with large ß values was transformed into an A-π-A' pattern, which displayed much smaller ß values. This feature makes these systems applicable as pH-triggered nonlinear optics (NLO) switches. In particular, protonation led to a decrease of the hyper-Rayleigh scattering first hyperpolarizabilities by at least one order of magnitude as well as to a decrease of the depolarization ratio, from about five for neutral species, which also supported the 1D-like NLO-phore nature, to about two for the protonated ones.

Geometric enantiomerism in cyclic compounds: chiral dibrominated 1,3-dioxanes.

The first geometric enantiomers in the cyclic compounds series are reported. The investigated compounds are 2,2-disubstituted-5-methyl-1,3-dioxane derivatives in which the substituents at position 2 bear chiral centers with identical substituents but with opposite configurations. The structure of the unlike isomers was determined from the solid state molecular structure of the compounds obtained by single crystal X-ray diffractometry and the enantiomers of these diastereoisomers were observed by chiral column HPLC base-line separation. The investigated compounds were obtained by a diastereoselective bromination reaction of the corresponding 2,2-dialkyl and 2,2-dibenzyl-5-methyl-1,3-dioxanes.

Nonlinear optical properties of flavylium salts: a quantum chemical study.

Ab initio calculations have been carried out to unravel the relationships between the structure and the first hyperpolarizability in flavylium derivatives, with the aim to design efficient second-order nonlinear optical (NLO) switching compounds. Large contrasts of the first hyperpolarizability have been obtained along the pH-controlled and photoinduced transformations for specific combinations of chemical substituents in the 4'- and 7-positions, which demonstrates that these multistate systems should behave as highly efficient molecular NLO switches.

Synthesis and structure of new 3,3,9,9-tetrasubstituted-2,4,8,10-tetraoxaspiro[5.5]undecane derivatives.

The configurational and conformational behavior of some new 3,3,9,9-tetrasubstituted-2,4,8,10-tetraoxaspiro[5.5]undecane derivatives with axial chirality was investigated by conformational analysis and variable temperature NMR experiments.

New [4.4]cyclophanes: molecular parallelograms, triangles, rhombuses, pentagons, and supramolecular constructions.

The fair or good yield synthesis of new [(4.4)(n)]cyclophanes (n = 1-5), starting from 1,4-bis(2-hydroxymethyl-5,5-dimethyl-1,3-dioxan-2-yl)benzene and several diacid-dichlorides, based on monomer and oligomer formation reactions (from 1 + 1 to 5 + 5), is reported. The structure and the complex architectures of the lattices for these cyclophanes are revealed by the X-ray molecular structure for five compounds, NMR investigations, and mass spectrometry measurements. Intramolecular and intermolecular CH-pi, p-pi, and pi-pi interactions are observed, both in solid state and solution.

Unsubstituted bicyclo[1.1.0]but-2-ylcarbinyl cations.

A synthesis for the unsubstituted bicyclo[1.1.0]but-2-ylmethanols (endo- and exo-9) from 1,3-butadiene has been developed. Solvolyses of their sulfonates 10 and 11 took entirely different courses, as the endo compound 10 gave rise exclusively to rearranged products such as cyclopent-3-en-1-ol (14), while the exo compound 11 underwent only the substitution of the tosylate group with complete retention of the exo-bicyclo[1.1.0]but-2-ylmethyl skeleton. Under solvolytic conditions, 10 reacted at very similar rates to the corresponding monocyclic substrate, that is, cyclopropylcarbinyl mesylate (19); in contrast, 11 reacted only three times as fast as n-butyl tosylate and about 1000-fold slower than 10. The nature of the bicyclo[1.1.0]but-2-ylcarbinyl cations has been probed by quantum chemical calculations. Whereas, the exo isomer (exo-18) corresponds to a local energy minimum, the endo isomer is only a transition state [endo-18(TS)] for an automerization of the nonclassical cyclopent-3-en-1-yl cation (13) and converts into 13 by a Wagner-Meerwein rearrangement. The most favorable isomerization of exo-18 also leads to 13 but via a transition state resembling the 2-vinylcycloprop-1-yl cation [25(TS)]. On the introduction of methyl groups at positions 1 and 3 of exo-18, the cation is no longer an energy minimum and it becomes a transition state [27(TS)] for an automerization of the nonclassical 1,3-dimethylcyclopent-3-en-1-yl cation (28). The large effect of the methyl substitution rationalizes the puzzling results of the previous product and rate studies, which utilized various substituted derivatives of bicyclo[1.1.0]but-2-ylcarbinyl sulfonates as substrates.