Conformational behavior of 3-borabicyclo[3.3.1]nonanes: 1. Study of molecular dynamics in 3-methoxy-7α-phenyl-1,5-dimethyl-3-borabicyclo[3.3.1]nonane

3-Methoxy-7α-phenyl-1,5-dimethyl-3-borabicyclo[3.3.1]nonane 5 in solution at room temperature exists in the double chair conformation, as shown by NMR studies. Increasing the temperature leads to an increase in the population of the chair–boat conformation. At decreased temperature hindered rotation around the B---O bond is observed for 5. Dissolving 5 in deuteropyridine leads to the reversible formation of complex 6, which exists in the chair–boat conformation. The chair–boat conformation is also the most stable one for chelate compound 7 with a tetracoordinated boron atom.     

Conformational study on some β-phenyl-α,β-unsaturated ketones

The conformation of three (E)-β-phenyl-α,β-unsaturated ketones and their corresponding (Z)-isomers 1, 2, and 3 was established by IR and ASIS. (Z)-1 and (E)-1 have exclusively the s-trans conformation. The two isomers of 2 occur in both conformations but there is a higher s-cis to s -trans ratio with the (Z) than with the (E)-isomer. (Z)-3 appears to exist exclusively in the s-cis conformation, the (E)-isomer has a small content of the s-trans conformation. It was concluded that the ASIS for H_b, is a measure of the s-cis content of the conformational equilibrium.     

Combination of asymmetric flow field-flow fractionation (AF4) and total-reflexion X-ray fluorescence analysis (TXRF) for determination of heavy metals associated with colloidal humic substances

To assess the structural variability of colloidal humic substances and the associated heavy metals an off-line coupling of asymmetric flow field-flow fractionation (AF⁴) with total-reflection X-ray fluorescence analysis (TXRF) is presented. AF⁴ allows a rather gentle separation of colloids with a minimum of interference and artifacts as no shear forces, drying, or interactions with a stationary phase are involved. After a calibration with suitable polymer particles of known molecular weight, the molecular weight distribution of colloidal humic substances between 1 and 10³ kDa can be assessed with AF⁴. The combination with TXRF permits a simultaneous multielement analysis after preconcentration of samples on the AF⁴ channel using an optimized buffer. The analysis of seepage and sewage water sample and a sewage sludge sample yielded continuous distributions of the molecular weight and the associated heavy metals. The potential of AF⁴-TXRF coupling for the study of metal ion exchange equilibria with colloids was demonstrated by spiking seepage water with various heavy metals and subsequent AF⁴-TXRF analysis of the heavy metals bound to the colloidal fraction (Cu, Cr, Zn, Ni, Co).     

Synthesis and characterization of macrocyclic compounds with a hydroxyl functional group

A novel [1+1] Schiff-base macrocyclic compound 3 has been synthesized from precursor 1, 1,3-bis(2'-formylphenoxy)-2-propanol, and precursor 2, resorcinol-bis(4-aminophenyl)ether, via condensation and cyclizaction using Ba2+ as template. The macrocycle 3 was further reduced giving saturated macrocycle 4. The structures of 3 and 4 were characterized by elemental analysis, 1H NMR, IR, and MS spectra, and their structures were determined via single crystal X-ray diffraction studies. X-ray diffraction analysis revealed that the macrocyclic compound 3 has a folded conformation, and the corresponding reduced product 4 adopts a twisted and folded conformation due to its flexible nature.     

The structure and chemistry of pebrolide,desacetylpebrolide and 1-deoxypebrolide,sesquiterpene benzoates from penicillium brevicompactum

The structure of three new drimane sesquiterpenes (1–3) has been established from chemical and spectroscopic evidence and by single crystal X-ray crystallographic analysis of 7. Ring B in the crystal of 7 is in a chair conformation, slightly distorted because of cis fusion to the lactone ring and because three β axial substituents are present. NMR evidence suggests that the preferred conformation in solution is similar.     

The bidentate complexes of (R,R)- and meso-α,α′-bis(trifluoromethyl)-9,10-anthracenedimethanol with cis-1-amino-2-indanol

The enantiorecognition of 1-aminoindane 3 and cis-1-amino-2-indanol 2 by (R,R)-α,α′-bis(trifluoromethyl)-9,10-anthracenedimethanol 1 is reported. The examination of the bidentate associations between 1 and 2 revealed that the cisoid conformation of 1 is responsible for the separation of the NMR signals. Two types of bimodal associations resulted from a cisoid conformation when meso-1 isomer was tested. Molecular mechanics modelling studies gave the possible structures of the associate species.     

Synthesis and conformational analysis of exo-and endo-7-substituted-3-azabicyclo[3.3.1]nonanes

The synthesis of some 7-substituted-3-azabicyclo[3.3.1]nonanes is described. Routes followed were the debenzoylation of the 7-benzoyl derivative 7 and the decarboxylation of the 7-carboxy compounds 21 and 27. The so-obtained 7-oxo-N-tosyl-3-azabicyclo[3.3.1]nonanes 8and 11 show an extremely low reactivity towards a series of nucleophilic reagents. From analysis of the ¹H NMR spectral data of a series of derivatives, the twin-chain conformation for the 7-exo compounds and the chair-boat conformation for the 7-endo compounds is indicated.     

NMR spectroscopy of cyclopentane derivatives: I. Cyclopentane and cyclopentanone

The deuterium-decoupled 100 MHz p.m.r. ¹³C-satellite spectra for cyclopentanone-2, 2,5,5-d₄ (2)) and cyclopentane-1,1,2,2,3,3-d₆ (5) have been determined at several temperatures and the LAOCOON 3 derived spectral parameters related to molecular conformation. For 2, the data were found to be consistent with the half-chair conformation; for 5, the data were fitted to an unrestricted pseudorotation model.     

Calcium Alginate Bead-mediated Enhancement of the Selective Recovery of a Lead Novel Antifungal Bacillomycin Variant

In the pursuit of new antifungal compounds, five coproduced lipopeptide variants (AF₁ to AF₅) from wild-type Bacillus subtilis RLID 12.1 were identified in our previous study. Out of five, AF₄ was identified as a novel lead molecule belonging to the bacillomycin family showing less cytotoxicity at its respective minimum inhibitory concentrations (MIC) evaluated against 81 strains of Candida and Cryptococcus species (including clinical isolates); besides this, AF₄ purified in the present study exhibited encouraging MIC values against 10 clinical mycelial fungi. Aiming for a selective production augmentation of AF₄ lipopeptide variant, a new fermentation media comprising malt extract (1.01%), dextrose (0.55%), peptone (1.79%), MnSO₄ (2 mM), and NaCl (0.5%) was formulated. Maximum production of 954.8?±?10.8 mg/L was achieved with 44% selectivity at 30 °C compared to unoptimized conditions (186.4?±?6.1 mg/L). Use of calcium alginate beads in the formulated media during the onset of lipopeptide production resulted in an augmentation in the selectivity of the most efficacious AF₄ variant to about 72% presumably due to attenuation of other coproduced lipopeptide variants AF₁ and AF₂. Difference in yield of lipopeptides varied with bead size, bead preparation ratios, and sodium alginate concentrations. Use of Ca-alginate beads in the upstream production process of the lead AF₄ variant may be considered as a novel strategy to address the potential challenge that may arise during the scale-up and downstream processing steps. Another significant finding derived from the study is that the proportion of bacillomycin variants of B. subtilis RLID 12.1 could be controlled by temperature and metal ions under static and shaking conditions.     

Chair-boat equilibria in bicyclo[3.3.1]nonane and some 3- and 3,7-substituted derivatives: Thermodynamic parameters and geometry of the conformers as obtained by molecular mechanics

ΔG-Values for conformational equilibria in 3,7-substituted bicyclo[3.3.1]nonanes have been obtained by means of epimerisation experiments (cc α bc) and by variable temperature ¹³C NMR (bc α bb). The results of these experiments fit well with those of molecular mechanics using the Schleyer force field. In bicyclo[3.3.1]nonane and 3β-substituted derivatives the cc conformation predominates; however, the bulky 3β-substituent t-butyl, is found to have a destabilizing effect. A 3α-substituent forces the substituted wing into the boat conformation. For the 3α,7α-substituted derivatives the conformational preferences depend on the size of the substituents: for 3α-methyl-7α-t-butylbicyclo[3.3.1]nonane the cb and t-bb conformers are of approximately equal enthalpy. The geometries, obtained by the calculations, show that the conformers of bicyclo[3.3.1]nonane (cc, bc and t-bb) are all distinctly flattened. The boat wings of bc conformers are not twisted to any extent. The t-bb is the most stable bb conformation. The influence of substitution at positions 3 or 7 is discussed in detail; in general, a bulky substituent such as t-butyl, affects the geometry of both wings of the ring system. The calculated geometries are in good agreement with the conclusions of previous ¹H NMR investigations.     

A molecular basis for glycosylation-induced conformational switching

Background: Asparagine-linked glycosylation has the capacity to greatly influence the structure and function of glycoproteins. In most cases, however, it is unclear specifically how the carbohydrate moiety interacts with the protein to influence its conformation.Results: A series of glycopeptides based on the critical A285 glycosylation site of the hemagglutinin glycoprotein from influenza virus was used as a model system to study the effects of asparagine-linked glycosylation. Derivatization of this peptide with a family of short carbohydrates reveals that subtle changes in the structure of the carbohydrate have a dramatic impact on peptide conformation. Modification of the hemagglutinin glycopeptide with a truncated version of the native carbohydrate induces a β-turn structure similar to the structure found in the native protein. Replacement of the C2 and C2′ N-acetyl groups of the carbohydrates with hydroxyl moieties results in a less well-ordered peptide conformation.Conclusions: It is likely that the N-acetyl groups of the carbohydrates have a critical role in promoting the more compact β-turn conformation through steric interactions with the peptide. This study has demonstrated that relatively small changes in carbohydrate composition can have dramatic ramifications on glycopeptide conformation.     

Binding studies of tetrathiafulvalene-calix[4]pyrroles with electron-deficient guests

The neutral meso-octamethylporphyrinogen derivative, tetraTTF-calix[4]pyrrole 1 (TTF=tetrathiafulvalene), acts as a multi-faceted receptor in that it interacts with an assortment of different guests in different ways. The conformation of receptor 1 can be reversibly switched between the 1,3-alternate conformation (i.e., 1, Fig. 1) and the cone conformation (i.e., 1·Cl⁻, Fig. 2) by the repetitive addition of chloride and sodium ions. In this paper, the results of detailed and systematic complexation studies involving both 1 and its chloride-bound complex, 1·Cl⁻, with a variety of guests are described. Receptor 1 binds quasi-planar nitroaromatic guests in its 1,3-alternate conformation, while release of these guests takes place upon addition of chloride anions. On the other hand, spherical fullerene guests are strongly bound by 1·Cl⁻. Finally, it was found that a bidentate guest, consisting of a quasi-planar 2,5,7-trinitro-9-dicyanomethylenefluorene moiety tethered to a spherical C₆₀ fullerene, could be recognized by receptor 1 in either its 1,3-alternate or its chloride-bound cone conformation, albeit through very different binding modes.     

Conformational analysis—XIII: Syn and anti [3.2]-, [3.3]-, [4.2]-, and [4.3]-metacyclophanes

While in [3.3]metacyclophane (19) the aromatic rings preferentially adopt the syn arrangement, its lower and higher homologues, i.e. [2,2]-, [3.2]-, [4.2], and [4.3]-metacyclophane (1, 6, 26 and 30), adopt the anti conformation. Substituted [m,n]metacyclophanes do not necessarily behave similarly to the parent hydrocarbons. Substituted compounds exhibiting a different conformation are [3.2]metacyclophane-1,11-dione (7) (syn), [3.3]metacyclophane-2,11-dione (24) and the corresponding bis[propylene thioacetal] (25) (anti), [4.2]metacyclophane-2,12-dione (27) (syn), and [4.3]metacyclophane-2,13-dione (31) (syn). Thus, the solution conformation of an [m.n]metacyclophane is sensitive both to chain length [m.n.] of the bridges and substitution. The ring inversion barriers determined by variable temperature ¹H NMR decrease with increasing length of the bridges and qualitatively correlate with the transanular strain present in the pertinent system.     

Conformational analysis of methylsuccinic acid by 1H NMR spectroscopy and circular dichroism

The pH-dependence of the ¹H NMR and Circular Dichroism (CD) spectra of 2-methylsuccinic acid was investigated. Both spectra undergo dramatic changes between pH 4 and 6, where both carboxylic groups become ionized. From the coupling constants of the tertiary proton with the assigned¹ diastereotopic methylene protons, it is concluded that below pH 4 the syn-clinal (2) and above pH 6 the anti-periplanar (1) conformation of methylsuccinic acid prevail. The diesters of methylsuccinic acid also assume mainly the syn-clinal conformation (2). The pH-dependence of the CD spectra is discussed in terms of conformation and/or ionization effects.     

Non-chair six-membered-ring conformations. Preference for a twist-boat (or skew) structure in α- -sorbopyranose derivatives

The conformational preferences for 2,3-O-isopropylidene-α- -sorbopyranose derivatives 3–6 were determined by using ¹H NMR data and empirical force field calculations. Proton NMR studies of 3–6 indicate that a twist-boat (or skew) conformation (³S₀) prevails over possible chair forms for each compound. Force-field calculations (MM2, MNDO, AM1) on a model 2,3-O-isopropylidene-α- -sorbopyranose system (18) indicate that the ³S₀ conformation is among the low-energy structures. X-Ray crystallographic analysis of α- -sorbopyranose sulfamate 3, a compound with potent anticonvulsant activity, demonstrates that the ³S₀ skew conformation is manifested in the solid state, as well.     

On the conformation of 6-ketononanolide and 1,4-cyclohexanedione in solution by dipole moment studies

The dipole moments of 6-ketononanolide (1) and its 2,4,7 and 8-Me derivatives (2–5) are found to be 1·8 – 1·9±0·2 D. Utilizing the known solid-state geometry of 1, a dipole moment of 1·6 D is calculated by the INDO quantum mechanical method. Thus the conformation of 1 in solution does not differ much from its solid-state conformation which is diamond-lattice derived with the CO groups 174° apart and in “Type III” positions. However, the IR spectrum of 1 in solution shows differences from that in the solid state (Nujol or KBr).The dipole moment of 1,4-cyclohexanedione (10) is calculated to be 1·2 D for the experimental 156° twist boat conformation (found in the solid-state). This is in excellent agreement with the experimental value found by several groups. 1,6-Cyclodecanedione (6), however, is found to have an experimental dipole moment of 0·7 D, as contrasted with a calculated value of 0 D for 180° opposed carbonyls.     

DFT,solution, and crystal conformation of eremophilanolides

The minimum energy conformation of five eremophilanolides (1–5) from the tubercles of Psacalium paucicapitatum was calculated using density functional theory (DFT) at the B3LYP/6-31G¹ level. Comparison of the experimental ¹H–¹H coupling constant values of 1–5 with those generated employing a generalized Karplus-type relationship using dihedral angles extracted from the DFT calculation and from the crystal structures for 1 and 3–5 shows good agreement. The A ring of 1–5 adopts an almost perfect chair conformation with the Me-14 group in an axial position and the Me-15 in an equatorial position.     

Circular dichroism—LI : Circular dichroism of derivatives of hop constituents containing a five-membered ring

The conformation of the cyclopentenones 5 to 8 is determined from their CD-spectra. The site of enolization and the conformation of cis- and trans-isohumulone (1 and 2) is determined with the help of the CD-spectra, the direction of enolization for the humulinic acids 3 and 4 is tentatively determined by the same method.     

DBU induced formation of 8-bromoguanosine dimer with three hydrogen bonds between the GG− base pairs

Upon hemideprotonation of 8-bromoguanosine (8-BrG) at the N1 position, induced by DBU, the adduct [8-BrG][8-BrG]^?[DBU–H]⁺ was formed. Slow evaporation of the 8-BrG methanol solution, in the presence of 0.5 equiv of DBU, yielded two polymorphic structures (1 and 2), where a neutral [8-BrG] (A) and N1 deprotonated, anionic 8-bromoguanosine [8-BrG]^? (B) were joined together through three intermolecular hydrogen bonds involving O6, N1 and C2–NH₂ sites. Such pairing gave planar GG^? dimers as the basic motif of crystal packing in both polymorphs. Both neutral and deprotonated guanosine molecules in the structure of 1 had the ribose units in a syn conformation. In the structure of polymorph 2, the N1 deprotonated guanosine molecule (B) retained the syn glycosidic conformation, while the non-deprotonated guanosine molecule (A) adopted the natural anti conformation of the ribose unit with respect to the nucleobase. Ribose rings revealed different puckering; only those of deprotonated molecules 1B and 2B possessed the usual C2′-endo envelope conformation. Crystal packing in both structures was guided by the highly complex H-bonded pattern. The CSD was searched for related structures, which are discussed with reference to polymorphs 1 and 2. ¹H and ¹³C NMR spectroscopic evidence is provided showing that the three H-bonded adduct [8-BrG][8-BrG]^?[DBU–H]⁺ was also formed in the highly H-bond competitive DMSO solution.     

The gas-phase conformation of 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane

The gas-phase conformation of the title compound (1) is discussed in reference to its photoelectron spectrum. The experimental lone-pair/lone-pair splitting (0.51 eV), when compared with that of similar diamines and with the results of three sets of MO calculations (MINDO/3, MNDO and STO-3G), leads to the conclusion that 1 exists in the chair-chair conformation. A remarkable sensitivity of the calculations to slight changes in the geometry is noted, and it is suggested that calculations of this type must include geometry-optimization. The question of through-space vs through-bond inteaction of the nitrogen lone pairs was explored by performing MNDO calculations in which the N-N resonance integrals were set to zero. These calculations indicate that in the chair-chair conformation the N-N interaction is mainly through-space. The ¹³CNMR and Ni(acac)₂-induced ¹³C shifts of 1 are discussed.