1H-, 31P- and 13C-NMR spectra of some 2-arylsulphonylamido-2-thiono-5-methyl-1,3,2-dioxaphospholanes

Some 2-arylsulphonylamido-2-thiono-5-methyl-1,3,2-dioxaphospholanes (1), containing two chiral centres, give NMR spectra in which splittings of the ¹H and ¹³C signals of the 5-methyl substituent and of the ³¹P signal indicate that they exist in an approximately 70:30% ratio of two racemic mixtures, Z and E respectively, diastereomeric to each other. These splittings were invariably observed for compounds 1a, containing a monosubstituted sulphonylamido group (Y = H) and various substituents at position 4′ of the aryl group, X = H, CH₃, OCH₃, F, CI and Br. The methylenic protons in position 4 of the phospholane ring are diastereotopic and therefore magnetically non-equivalent. Benzene-induced shifts were measured for the Z isomers of compounds 1a, X = H, F and for compound 1b, containing an N-disubstituted sulphonylamido group (Y = CH₃) and X = H; the tentative interpretation of these shifts places the more shielded diastereotopic methylene proton on the same side of the ring as the 5-methyl substituent. The H? P and H? H coupling constants indicate that the preferred conformation of the dioxaphospholane ring should be a ‘twisted envelopey’ shape with the 5-methyl substituent in the equatorial position.     

Diastereotopic splitting in the 13C NMR spectra of sulfur homofullerenes and methanofullerenes with chiral fragments

Using gauge‐invariant atomic orbital PBE/3ζ quantum chemistry approach, ¹³C NMR chemical shifts and diastereotopic splittings of sp² fullerenyl carbons of a number of sulfur homofullerenes and methanofullerenes have been predicted and discussed. An anisochrony of fullerene carbons is caused by a chiral center of attached moieties. Clearly distinguishable diastereotopic pairs (from 8 to 11) of fullerenyl carbons of homofullerenes were observed. Unambiguous assignments of ¹³C NMR chemical shifts were performed, and diastereotopic splittings of methanofullerenes were observed for α, β and γ to a functionalization site. Copyright © 2013 John Wiley & Sons, Ltd.     

Carbo[n]helicenes Restricted to Enantiomerize: An Insight into the Design Process of Configurationally Stable Functional Chiral PAHs

The most important stereodynamic feature of carbo[n]helicenes is the interconversion of their enantiomers. The Gibbs activation energy (ΔG^≠(T)) of this process, which determines the rate of enantiomerization, dictates the configurational stability of [n]helicenes. High values of ΔG^≠(T) are required for applications of functional chiral molecules incorporating [n]helicenes or helicene substructures. This minireview provides an overview of the mechanism, recent developments, and factors affecting the enantiomerization of [n]helicenes, which will accelerate the design process of configurationally stable functional chiral molecules based on helicene substructures. Additionally, this minireview addresses the misconception and irregularities in the recent literature on how the terms “racemization” and “enantiomerization” are used as well as how the activation parameters are calculated for [n]helicenes and related compounds.     

Triggering G-Quadruplex Conformation Switching with [7]Helicenes

The dynamic interplay between two types of chiral structures; fully conjugated racemic hetero[7]helicenes and DNA strands prone to fold into G-quadruplex structures is described. Both the [7]helicenes and the G-quadruplex DNA structures exist in more than one conformation in solution. We show that the structures interact with and stabilise each other, mutually amplifying and stabilising certain conformations at increased temperatures. The [7]helicene ligands L1 and L2 stabilise the parallel conformation of k-ras significantly, whereas hybrid (K⁺) and antiparallel (Na⁺) h-telo G-quadruplexes are stabilised upon conformational switching into altered G-quadruplex conformations. Both L1 and L2 induce parallel G-quadruplexes from hybrid structures (K⁺) and L1 induces hybrid G-quadruplexes from antiparallel conformations (Na⁺). Enantioselective binding of one helicene enantiomer is observed for helicene ligand L2 , and VTCD melting experiments are used to estimate the racemisation barrier of the helicene.     

Investigations of dithienylglycolic esters—IV : Solvent effects on the chemical shift differences of the diastereotopic thienyl protons in an asymmetric 2,2′-dithienylglycolic ester

The chemical shift differences (Δν) of the diastereotopic thienyl protons of 1-phenyl (-d₅) ethyl 2,2′-dithienylglycolate have been measured for different solvents and at different temperatures. The solvent dependence of the Δν's are interpreted as being due mainly to solvent shifts of the diastereotopic protons.     

Structure-based predictions of H NMR chemical shifts of sesquiterpene lactones using neural networks

In this work the prediction of ¹H NMR chemical shifts of CH_n protons of sesquiterpene lactones by means of neural networks is described. This method is based on the incorporation of experimental chemical shifts of protons of sesquiterpene lactones as additional memory of an associative neural network system previously trained with chemical shifts of other organic compounds. One advantage of this method is its ability to distinguish between CH₂ diastereotopic protons belonging to rigid substructures since stereochemistry is considered. This is achieved via the automatic conversion of the 2D structure diagram into a 3D molecular structure. The predicted ¹H NMR chemical shifts of the sesquiterpene lactones showed a high level of accuracy. This is the first report on a fully automatic proton assignment of structures of sesquiterpene lactones of an accuracy that allows its use in structure elucidation.     

The Stereochemistry of 1,2,3‐Triols Revealed by 1H NMR Spectroscopy: Principles and Applications

The conformational compositions of the tris(α‐methoxy‐α‐phenylacetic acid) ester derivatives of 1,2,3‐prim,sec,sec‐triols are presented. These conformations have been determined by theoretical and experimental data (i.e., energy‐ and chemical‐shift calculations, circular dichroism (CD) experiments, coupling‐constant analysis, enantioselective deuteration experiments, and low‐temperature NMR spectroscopic studies). A detailed analysis of the anisotropic effects due to the most significant conformers in the ¹H NMR spectra supported the correlation between the ¹H NMR spectra (Δδ^RS value of H(3′) and |Δ(Δδ^RS)| parameters) and the absolute configuration of the substrate. The study also allows the identification of the pro‐R and pro‐S methylene protons from their vicinal coupling constants and relative chemical shifts.     

Counterion influence on chemical shifts in strychnine salts

The highly toxic plant alkaloid strychnine is often isolated in the form of the anion salt of its protonated tertiary amine. Here, we characterize the relative influence of different counterions on ¹H and ¹³C chemical shifts in several strychnine salts in D₂O, methanol‐d₄ (CD₃OD), and chloroform‐d (CDCl₃) solvents. In organic solvents but not in water, substantial variation in chemical shifts of protons near the tertiary amine was observed among different salts. These secondary shifts reveal differences in the way each anion influences electronic structure within the protonated amine. The distributions of secondary shifts allow salts to be easily distinguished from each other as well as from the free base form. Slight concentration dependence in chemical shifts of some protons near the amine was observed for two salts in CDCl₃, but this effect is small compared with the influence of the counterion. Distinct chemical shifts in different salt forms of the same compound may be useful as chemical forensic signatures for source attribution and sample matching of alkaloids such as strychnine and possibly other organic acid and base salts. Copyright © 2013 John Wiley & Sons, Ltd.     

Folding and Anion‐Binding Properties of Fluorescent Oligoindole Foldamers

A series of oligoindole foldamers 1 a – d that are highly fluorescent were prepared by using a biindole derivative as the repeating unit, and their folding and anion‐binding properties were revealed by ¹H NMR and fluorescence spectroscopy. The oligoindoles exist in an extended conformation, but adopt a compact helical structure in the presence of an anion. The anion is entrapped inside the tubular cavity of the helical strand, comprising four aryl units per turn, by multiple hydrogen bonds with the indole NHs. These structural features were confirmed by ¹H NMR and fluorescence spectroscopy. When folded by anion binding, 1 b – d show characteristic downfield shifts of the NH signals and upfield shifts of the aromatic CH signals by Δδ=0.1–1.0 ppm. The average chemical shift for all the aromatic signals of 1 a – d is more upfield shifted as the chain lengthens, as anticipated from the degree of overlapped aromatic surfaces in the helical strand. Moreover, 1 a – d are strongly fluorescent in the absence of an anion. Upon binding an anion such as a chloride, the shorter oligoindoles 1 a and b lead to negligible change in the emission spectra, whereas the longer ones 1 c and d result in dramatic changes, that is, large hypochromic and bathochromic shifts (Δλ=65 and 70 nm) of the emission band, confirming the helical folding. The association constants (K_a) between oligoindoles and tetrabutylammonium chloride strongly depend on the chain length; <1 M ^?1 for 1 a , 630 M ^?1 for 1 b , 1.1×10⁵ M ^?1 for 1 c , and 2.9×10⁵ M ^?1 for 1 d in 20 % (v/v) MeOH/CH₂Cl₂ at 24±1 °C. In addition, the association constants of 1 c and 1 d with other anions such as fluoride, bromide, iodide, azide, cyanide, acetate, and nitrate are determined to be in the order of 10³–10⁶ M ^?1 under the same conditions.     

Conformational Analysis of the cis- and trans-Isomers of FK506 by NMR and Molecular Dynamics

The potent immunosuppressant drug FK506 ( 2 ) has been examined by ¹H- and ¹³C-NMR spectroscopy and NOE-restrained molecular dynamics to elucidate the conformation in solution. A combination of two- and three-dimensional NMR techniques was used to completely assign the ¹H- and ¹³C-NMR chemical shifts of the two configurational isomers resulting from the cis-trans isomerization about the single amide bond. Hetero- and homonuclear coupling constants were measured to assign the diastereotopic methylene protons at C(16), C(18), and C(23). Intramolecular H? H distances were defined from NOESY spectra recorded at ?30° in CDCl₃ and used as constraints in molecular-dynamics simulations. The conformational preferences of 2 in solution are discussed in light of the constitutional features recently proposed to be necessary for binding and activity.     

Nanographene Imides Featuring Dual‐Core Sixfold [5]Helicenes

A novel kind of nanographene imide, namely pentaperylene decaimides (PPD) featuring dual‐core sixfold [5]helicenes and ten imide groups, was efficiently obtained. Among the possible 28 stereoisomers, which include 14 pairs of enantiomers, only one pair of enantiomers was obtained selectively which could be separated by chiral HPLC. Single‐crystal X‐ray diffraction analyses revealed that it exhibits a D₂‐symmetric “four‐bladed propeller” conformation composed of conjoined double “three‐bladed propeller”, which is very stable and could not convert into other conformations even when heated up to 200 °C. Meanwhile, enantiomerically pure PPD also exhibits an excellent resistance to thermally induced racemization, which makes it a promising candidate for various applications in chiral material science.     

Cyclobishelicenes: Shape-Persistent Figure-Eight Aromatic Molecules with Promising Chiroptical Properties

Cyclobis[n]helicenes (n=3 or 5) are chiral D₂-symmetric π-conjugated macrocycles with stable lemniscular, or figure-eight, shapes. The conformational analysis of five different cyclobis[n]helicenes revealed that these molecules can only exist as their lemniscular conformers with high barriers to enantiomerization (>200 kJ mol⁻¹). The enantiomers of a cyclobis[5]helicene were resolved by HPLC and their unusual chiroptical properties were attributed to the inherent chirality of their macrocyclic figure-eight.     

A new approach to the synthesis of ‘chiral’ glycine

The stereospecific coordination of N-benzylglycinate ion in ΔR-(N-benzylglycinato)bis(ethylene-diamine) cobalt(III) chloride has been determined by X-ray crystallographic analysis, rotatory dispersion and ¹H NMR spectroscopy. The chiral glycinato-N and Co centres influence the relative rates of exchange of the diastereotopic glycine methylene protons in basic solution (pH 10·5 with Na₃PO₄inD₂O) and a synthesis supposedly of S-(N-benzyl)- 2-²H glycinate ion ≈ 80% optical purity) has been achieved.     

Helical β-isoindigo-Based Chromophores with B−O−B Bridge: Facile Synthesis and Tunable Near-Infrared Circularly Polarized Luminescence

It is essential to create organic compounds that exhibit circularly polarized luminescence (CPL) in the near-infrared (NIR) range. Helicene-type emitters possess appealing chiroptical features, however, such NIR molecules are scarce due to a paucity of synthetic strategies. Herein, we developed a series of helical β-isoindigo-based B−O−B bridged aza-BODIPY analogs that were synthesized conveniently. The reaction of diimino-β-isoindigo with a heteroaromatic amine produced a restricted ligand cavity, which triggered off the generation of a B−O−B bridge. The B−O−B bridge led to distorted conformations that satisfy the helical requirements, resulting in excellent spectroscopic and chiroptical properties. Tunable CPL with the highest luminescence dissymmetry factor (g_lum) of 1.3×10⁻³ and a CPL brightness (B_CPL=11.5 M⁻¹ cm⁻¹) in the NIR region was achieved. This synthetic approach is expected to offer a new opportunity to chiral chemistry and increase flexibility for chiroptical tuning.     

Functionally Rigid and Degenerate Molecular Shuttles

The preparation and dynamic behavior of two functionally rigid and degenerate [2]rotaxanes ( 1⋅ 4 PF₆ and 2⋅ 4 PF₆) in which a π-electron deficient tetracationic cyclophane, cyclobis(paraquat-p-phenylene) (CBPQT⁴⁺) ring, shuttles back and forth between two π-electron-rich naphthalene (NP) stations by making the passage along an ethynyl-phenylene-(PH)-ethynyl or butadiyne rod, are described. The [2]rotaxanes were synthesized by using the clipping approach to template-directed synthesis, and were characterized by NMR spectroscopic and mass spectrometric analyses. ¹H NMR spectra of both [2]rotaxanes show evidence for the formation of mechanically interlocked structures, resulting in the upfield shifts of the resonances for key protons on the dumbbell-shaped components. In particular, the signals for the peri protons on the NP units in the dumbbell-shaped components experienced significant upfield shifts at low temperatures, just as has been observed in the flexible [2]rotaxanes. Interestingly, the resonances for the same protons did not exhibit a significant upfield shift at 298 K, but rather only a modest shift. This phenomenon arises from the much reduced binding of the ethynyl-NP unit compared to the 1,5-dioxy-NP unit. This effect, in turn, increases the shuttling rate when compared to the 1,5-dioxy-NP-based rotaxane systems investigated previously. The kinetic and thermodynamic data of the shuttling behavior of the CBPQT⁴⁺ ring between the NP units were obtained by variable-temperature NMR spectroscopy and using the coalescence method to calculate the free energies of activation (ΔG_c^≠) of 9.6 and 10.3 kcal mol⁻¹ for 1⋅ 4 PF₆ and 2⋅ 4 PF₆, respectively, probed by using the rotaxane's α-bipyridinium protons. The solid-state structure of the free dumbbell-shaped compound ( 3 ) shows the fully rigid ethynyl-PH-ethynyl linker with a length (8.1 Å) twice as long as that (3.8 Å) of the butadiyne linker. Full-atomistic simulations were carried out with the DREIDING force field (FF) to probe the degenerate molecular shuttling processes, and afforded shuttling energy barriers (ΔG^≠=10.4 kcal mol⁻¹ for 1⋅ 4 PF₆ and 2⋅ 4 PF₆) that are in good agreement with the experimental values (ΔG_c^≠=9.6 and 10.3 kcal mol⁻¹ for 1⋅ 4 PF₆ and 2⋅ 4 PF₆, respectively, probed by using their α-bipyridinium protons).     

A Novel Thermocell System Using Proton Solvation Entropy

The entropy change associated with proton-coupled electron transfer (PCET) reactions significantly enhance the Seebeck coefficient (S_e) of thermocells. A redox pair of [Ru(H_xim)₆]^2+/3+ (Him=imidazole, x=0≈1) releases three protons in their one-electron redox reactions in thermocells, which gave a remarkably high S_e of −3.7 mV K⁻¹ as confirmed by temperature-dependent square wave voltammetry. The value of S_e is proportional to the redox reaction entropy (ΔS_rc), which increased with the number of dissociating protons. This result demonstrates the utility of PCET reaction toward efficient thermoelectric conversion.     

Enhanced Optical Properties of Azaborole Helicenes by Lateral and Helical Extension

The synthesis and characterization of laterally extended azabora[5]-, -[6]- and -[7]helicenes, assembled from N-heteroaromatic and dibenzo[g,p]chrysene building blocks is described. Formally, the π-conjugated systems of the pristine azaborole helicenes were enlarged with a phenanthrene unit leading to compounds with large Stokes shifts, significantly enhanced luminescence quantum yields (Φ) and dissymmetry factors (g_lum). The beneficial effect on optical properties was also observed for helical elongation. The combined contributions of lateral and helical extensions resulted in a compound showing green emission with Φ of 0.31 and |g_lum| of 2.2×10⁻³, highest within the series of π-extended azaborahelicenes and superior to emission intensity and chiroptical response of its non-extended congener. This study shows that helical and lateral extensions of π-conjugated systems are viable strategies to improve features of azaborole helicenes. In addition, single crystal X-ray analysis of configurationally stable [6]- and -[7]helicenes was used to provide insight into their packing arrangements.     

A π-Extended Pentadecabenzo[9]Helicene

A novel chiral nanographene (i.e. EP9H ) with a pentadecabenzo[9]helicene core fragment has been synthesized and fully characterized. Single-crystal X-ray diffraction unambiguously confirms the helical structure. The fluorescence emission of EP9H is located in the near infrared region (λ_em=684 nm) with a medium quantum yield (0.10) for helicene derivatives. Cyclic voltammetry reveals its seven quasi-reversible redox states from −2 to +5. Furthermore, enantiopure EP9H displays distinct CD signals in a broad spectral range from 300 to 700 nm. Notably, compared to the reported small organic molecules, EP9H displays an outstanding |g_lum| value of 4.50×10⁻² and B_CPL as 304 M⁻¹ cm⁻¹.     

Multiple Fused Anthracenes as Helical Polycyclic Aromatic Hydrocarbon Motif for Chiroptical Performance Enhancement

Polycyclic aromatic hydrocarbons consisting of three fused anthracene units were designed as new π‐conjugated compounds having helical structures. These expanded helicenes were synthesized by Pt‐catalyzed cycloisomerization of the corresponding ethynyl‐substituted precursors. The nonplanar and helical structure was confirmed by X‐ray analysis and DFT calculations, and the barrier to helical inversion was estimated to be 34 kJ mol^?1. The enantiomers of the diphenyl derivative were successfully resolved by chiral HPLC. Enantiopure samples showed good chiroptical performance in the CD (|Δ?| 1380 L mol^?1 cm^?1) and CPL (|g_lum| 0.013) spectra, and these values were considerably large for simple organic molecules. The unique chiroptical properties are discussed on the basis of the molecular structure and the electronic state with the aid of time‐dependent DFT calculations.     

Spin–Orbit Charge-Transfer Intersystem Crossing in Anthracene–Perylenebisimide Compact Electron Donor–Acceptor Dyads and Triads and Photochemical Dianion Formation

Perylenebisimide ( PBI )–anthracene ( AN ) donor–acceptor dyads/triad were prepared to investigate spin–orbit charge-transfer intersystem crossing (SOCT-ISC). Molecular conformation was controlled by connecting PBI units to the 2- or 9-position of the AN moiety. Steady-state, time-resolved transient absorption and emission spectroscopy revealed that chromophore orientation, electronic coupling, and dihedral angle between donor and acceptor exert a significant effect on the photophysical property. The dyad PBI-9-AN with orthogonal geometry shows weak ground-state coupling and efficient intersystem crossing (ISC, Φ_Δ=86 %) as compared with PBI-2-AN (Φ_Δ=57 %), which has a more coplanar geometry. By nanosecond transient absorption spectroscopy, a long-lived PBI localized triplet state was observed (τ_T=139 μs). Time-resolved EPR spectroscopy demonstrated that the electron spin polarization pattern of the triplet state is sensitive to the geometry and number of AN units attached to PBI . Reversible and stepwise generation of near-IR-absorbing PBI radical anion ( PBI^−⋅ ) and dianion ( PBI²⁻ ) was observed on photoexcitation in the presence of triethanolamine, and it was confirmed that selective photoexcitation at the near-IR absorption bands of PBI^.− is unable to produce PBI²⁻ .