13C NMR spectroscopy of four tertiary methyl norbornenols and norbornanols

Carbon chemical shifts and direct ¹³C? ¹H coupling constants of 2-endo-methyl-5-norbornen-2-exo-ol, 2-exo-methyl-5-norbornen-2-endo-ol, 2-endo-methylnorbornan-2-exo-ol and 2-exo-methylnorbornan-2-endo-ol have been measured from single samples using a dual probe pulse Fourier transform method.     

Carbon-13 NMR studies on some 5-substituted quinoxalines

Eleven 5-substituted quinoxalines (NO₂, NH₂, COOH, OCH₃, CH₃, OH, F, Cl, Br, I, CN, the latter five not reported previously) have been synthesized by standard methods. Their ¹³C NMR spectra have been measured in DMSO-d₆ and assigned on the basis of substituent parameters, by line widths and by intensities. The chemical shifts compare favorably with those calculated using benzene substituent parameters, and are very close to those of corresponding carbons in 1-substituted phenazines. The correlation with the chemical shifts of the corresponding positions in 1-substituted naphthalenes is also close except for those of carbons 4a and 8a in the quinoxalines which, due to their proximity to nitrogen, are downfield (in some cases 12 ppm) of the signals of the corresponding carbons in naphthalene. 5-Fluoroquinoxaline was also measured in CDCl₃, CD₃COCD₃, CD₃CN, CD₃OD, C₆D₆ and CD₃COOD. In all solvents an abnormally low ²J(CF) (～ 12 Hz) was found for C-4a and no C? F spin-spin splitting could be detected for the three-bond coupling of C-8a. Similar abnormalities were found in 2-fluoroaniline and 2-fluoroacetanilide. There are linear relationships between the Q parameter of the substituent and the chemical shift of carbons 4a, 5 and 6. A linear relationship also exists between the chemical shift of C-8 (‘para’ position) and the Hammett σ_p parameter of the substituent.     

Ion–molecule reactions in the gas phase. XVIII.—nucleophilic substitution of diastereomeric norborneols,norbornyl acetates and benzoates under ammonia chemical ionization

The comparative behaviour of the endo- and exo-norborneols and diastereomeric derivatives (acetates and benzoates) towards the NH₃/NH₄⁺ system was investigated. It appears that the proton affinity (PA) of the substrate relative to Pa(NH₃) strongly influences competition between the protonation and nucleophilic substitution processes yielding the MH⁺ and [M + NH₄ ? H₂O]⁺ ions, respectively. Tandem mass spectrometry was used to compare collision-activated dissociation spectra of [M + NH₄ ? H₂O]⁺ with those of analogous endo- and exo-norbornylamines protonated in the source. This demonstrates that an S_Nimechanism occurs specifically for the isomeric norborneols; in contrast, for acetates and benzoates, stereospecific S_Ni and S_N2 pathways take place for exo and endo derivatives, respectively. This particular behaviour is explained by considering the steric effect induced by the endo-H at C(6). In addition, the competitive decompositions of [M + NH₄ – H₂O]⁺ into NH₄⁺ and [C₇H₁₁]⁺ daughter ions are consistent with the formation of a proton-bound complex intermediate. The observed stereochemical effects for these dauther ions are rationalized by means of arguments based on the estimated heats of formation of the transition states, which is lower for the exo-norbonyl protonated amine, consistent with anchimeric assistance, rather than a stepwise pathway which is proposed for the endoisomer.     

A carbon-13 NMR study of benzonorbornene isomers

The carbon-13 NMR spectra of a series of exo-and endo-epimers of 2-substituted benzonorbornene (2-substituent = OH, OCHO, Br, NH₂, NHMe or NMe₂) have been examined. The spectra are readily assigned by comparison with the coupled and off-resonance proton decoupled spectra as well as by the use of shift reagents. Interesting and diagnostic features of the spectra allow the distinction between epimers.     

Study on 15N NMR of lithium sudan I complex

The ¹⁵N chemical shift have been measured for α-¹⁵N-labelled phenylazo-2-naphthol and its lithium complex. The change of the ¹⁵N chemical shift on coordination of the azo nitrogen to lithium appears to be related to those of protonation of the same nitrogen. The chemical shifts of azo form and hydrazone form have been calculated according to the weighted δ_N and ¹J_NH of different fractions. It is concluded that there is a bond formation between Li and N atoms.     

Fast Proton Exchange in Histidine: Measurement of Rate Constants through Indirect Detection by NMR Spectroscopy

Owing to its imidazole side chain, histidine participates in various processes such as enzyme catalysis, pH regulation, metal binding, and phosphorylation. The determination of exchange rates of labile protons for such a system is important for understanding its functions. However, these rates are too fast to be measured directly in an aqueous solution by using NMR spectroscopy. We have obtained the exchange rates of the NH₃⁺ amino protons and the labile NH^ε2 and NH^δ1 protons of the imidazole ring by indirect detection through nitrogen‐15 as a function of temperature (272 K<T<293 K) and pH (1.3<pH<4.9) of uniformly nitrogen‐15‐ and carbon‐13‐labeled L ‐histidine ? HCl ? H₂O. Exchange rates up to 8.5×10⁴ s^?1 could be determined (i.e., lifetimes as short as 12 μs). The three chemical shifts δ_Hi of the invisible exchanging protons H_i and the three one‐bond scalar coupling constants ¹J(N,H_i) could also be determined accurately.     

14N NMR of amminecobalt(III) compounds

Directly detected ammine ¹⁴N NMR chemical shifts of 20 amminecobalt(III) compounds are reported. The coordination shifts, δ_CS = δ_coord ? δ_free, are in all cases negative and range from ?4.4 ppm for the trans ammine ligand in [Co(NH₃)₅(CH₃)]²⁺ to ?73.6 ppm for the trans ammine ligand in [Co(NH₃)₅(F)]²⁺. Among the ligands studied, the NO₂^? ligand is unique in that it exerts a significant cis influence. The regularity in trans or cis influences upon the ammine nitrogen chemical shifts provides a basis for assignments in cases where this cannot be deduced from intensity ratios. Copyright © 2003 John Wiley & Sons, Ltd.     

Protein-Loop Mimetics: A Diketopiperazine-Based Template to Stabilize Loop Conformations in Cyclic Peptides Containing the NPNA and RGD Motifs

We explore here an approach to mimic the structures and biological functions of protein loops in small synthetic molecules, by grafting the loop of interest onto an organic template comprising a bicyclic diketopiperazine, prepared by the formal coupling of (2S,4S)-4-aminoproline (Pro(NH₂)) and aspartic acid (Asp). The Fmoc-protected template 4 is used to prepare cyclo(-Ala¹-Asn²-Pro³-Asn⁴-Ala⁵- Ala⁶-Temp-) ( 5 ) and cyclo(-Ala¹-Arg²-Gly³-Asp⁴-Temp-) ( 6 ) (where Temp = template derived from 4 ), containing the Asn-Pro-Asn-Ala (NPNA) and Arg-Gly-Asp (RGD) motifs. The conformational properties of these molecules are studied in aqueous solution by NMR and simulated-annealing methods. The NPNA motif, an immunodominant epitope on the circumsporozoite surface protein of the malaria parasite Plasmodium falciparum, is shown to adopt a stable type-I β-turn in 5 . The template in 5 adopts a preferred conformation with Pro(NH₂)χ₁ ≈? ?35° and the Asp moiety χ₁ ≈? 70°. A different template conformation is inferred for 6 , with Pro(NH₂)χ₁ ≈? 0°, but the ARGD loop appears by NMR to undergo rapid conformational averaging. Solid-phase binding assays reveal that 6 displays modest antagonist activity towards both the integrin α_IIbβ₃ and α_vβ₃ receptors.     

NMR studies on bridged polycyclic compounds: Spin system transitions due to induced solvent shifts

An NMR study of some bridged bicyclo and tricyclo compounds yielded unusual spectra with respect to solvent effects and virtual coupling. As is the general case for most large polycyclic systems a complete analysis of the spectrum is not possible and the structural details derived from NMR are based on a partial analysis of the spectrum. If the accessible resonances correspond to protons adjacent to methylene groups, the resonance patterns and the chemical shifts may be strongly dependent upon solvent. For 6-endo-hydroxy, bicyclo[2.2.1]heptane-2,endo-carboxylic acid lactone (1), 6-endo-hydroxy, 2-exo-methyl-bicyclo[2.2.2]octane-2-endo-carboxylic acid lactone (2), and exo-3,4,exo-8,9-diepoxy, endo-tricyclo[5,2,1,0^2,6]decane (3), resonances for each fall in this class and the change induced by solvent are attributed to virtual coupling as well as a change in the overall splitting pattern.     

A Tricyclic Template Derived from (2S,4R)-4-Hydroxyproline for the Synthesis of Protein Loop Mimetics

A tricyclic diketopiperazine, formally derived by coupling (2S,4S)-4-aminoproline (Pro(NH₂)) and (2S,4R)-4-(carboxymethyl)proline (Pro(CH₂COOH)), is synthesized starting from readily available (2S,4R)-4-hydroxyproline. The resulting tricyclic template has carboxy and amino groups to which a peptide chain may be attached. The Fmoc-protected template 5 is incorporated into the cyclic molecule cyclo(-Ala¹-Asn²-Pro³-Asn⁴-Ala⁵-) ( 6 ) where Pro(NH₂)⁷ = Pro(CH₂COOH)⁸ represents the template, using solid-phase peptide synthesis with cyclization in solution. The molecule is shown by NMR and dynamic simulated annealing methods to adopt a preferred conformation in aqueous solution, which includes an extended backbone at the residues Asn²-Pro³-Asn⁴, and a type-Iβ-turn at . These studies show that this novel template may be used in the synthesis of cyclic peptide and protein mimetics having defined secondary structure in aqueous environments.     

Carbon-13 NMR chemical shifts in some substituted 1,2,4-triazol-3-ones

Carbon-13 NMR data for 15 substituted 1,2,4-triazol-3-ones are presented and discussed with regard to enolization in the neutral molecules. The coupling constant and chemical shift data show that the proton at N-2 is not exchanging rapidly in the DMSO-d₆ solvent. Using D₂O? OD^? as a solvent, it is found that the C-3 and C-5 resonances are shifted downfield by nearly the same amount, suggesting that the proton at N-4 is being removed. Enolization in the neutral molecules does not occur to any significant extent.     

NMR study of organosilicon compounds. III—Silicon-29, nitrogen-14, carbon-13 and proton NMR spectra of silylakylamines

²⁹Si, ¹⁴N ¹³C and ¹H NMR data are presented for a series of homologous (methylethoxysilyl)alkylamines of the type (CH₃)_3?n(C₂H₅O)_nSi(CH₂)_mNH₂(n=o to 3; m = 1 to 4). The measured ¹³C and ¹H chemical shifts correlate with the total net charges Q_A on the corressponding atoms, estimated by the Del Re method. ¹⁴N and ²⁹Si chemical shifts which do not show simple linear relationships to the charges are found to correlate with the relative basicities of the compounds. The influence of the remote substituent (? NH₂ and others) on the ₂₉Si chemical shifts is shown to depend on the number and nature of substituents directly on the silicon atom. Argyments for d-orbital participation in the Si? O bounds are given. The chemical shifts of ²⁹Si, ¹⁴N and ₁₃C nuclei are not consistent with the fromation of intramolecular ‘long bonds’ between the solicon and nitrogen atoms in aliphatic silymethylamines.     

The 1H NMR spectra of some norbornene derivatives,a LIS study

The ¹H NMR spectra of 2-exo-hydroxymethyl-3-endo-methylnorbornene and the corresponding 2-endo-3-exo isomer have been completely assigned with the aid of lanthanide reagents. This enabled a full analysis of the unusual spectrum of 2-exo-hydroxy-methyl-3-endo-methylnorbornene to be undertaken, confirming the proposed structure. The ΔEu values for 2-exo-hydroxymethyl-3-endo-methylnorbornene and the 2-endo-3-exo-isomer have been used to test the effect of rotational averaging on the calculated pseudo contact shifts. Good agreement is obtained for a dynamic model in which the Eu atom exchanges between two sites on the oxygen atom of the OH bond, and in which the rotational equilibrium about the CH? CH₂OH bond is explicitly considered.     

Proton NMR studies of reduced porphyrin compounds

Detailed ¹H NMR studies of ms tetraphenylchlorins (H₂TPC), new amino- and hydroxypyrroline substituted ms tetraphenylchlorins and ms tetraphenylisobacteriochlorins (H₂TPisoB) are presented and discussed. The results obtained are consistent with the general aspects of the ring current models as applied to the parent porphyrins. According to proton chemical shifts a gradual reduction in the magnitude of the ring current is observed in the order ms tetraphenylporphyrin (H₂TPP) > H₂TPC> ms tetraphenylbacteriochlorin (H₂TPB) > H₂TPisoB. The ¹H NMR spectra show chemical non-equivalence of the pyrroline ring protons due to adjacent substituents, and effects of steric constraints on the aminoalkyl substituents due to the close vicinity to the meso phenyl rings. The non-equivalence of the methylene protons of the pyrroline ring produces geminal coupling between the two methylene protons and vicinal coupling with the adjacent pyrroline proton, more pronounced in H₂TPC? OH and in . Restricted configuration of the methylene groups in the ethyl groups of H₂TPC? C(H)(CH₃)N(CH₂CH₃)₂ produces observable geminal coupling between the methylene protons. ¹H NMR reveals the difference between two types of meso phenyls in the chlorins, and three types of meso phenyls in isobacteriochlorins, as reflected in the chemical shifts of the o-phenyl protons.     

NMR-Untersuchungen an Dicyclopentadienderivaten: II.—13C-NMR: γ-gauche-Effekt in Abhängigkeit von der exo/endo-Isomerie an Dicyclopentadien diolen

The ¹³C FT n.m.r. spectra of some exo- and endo-dihydro- and tetrahydrodicyclopentadiene-9,10-diols(exo/exo or endo/endo) are studied and the chemical shifts of the C-atoms are assigned by application of Eu(fod)₃ paramagnetic shift investigations and additional chemical shift parameters. Thus relatively strong γ-effects up to 12,8 ppm were observed for the C-atoms 4, 5, 7, 9, 10 and 1, 3, dependent on the exo/endo configuration of the OH-groups and the attached 5-ring, giving an interesting insight into the gemetry of these norbornane systems.     

Chemical ionization mass spectra of some 2-norbornyl derivatives

Chemical ionization mass spectra of exo- and endo-2-norbornanols and their phenylurethane derivatives have been obtained with several reactant ions. Small differences are noted in the abundances of norbornyl and [M+H]⁺ ions for the phenylurethane derivatives: more norbornyl ions with the exo compounds. Relative rate constants for decomposition of [M+H]⁺ ions, k_exo/k_endo ? 1-2. No evidence was found for s?-participation in the decomposition of these ions. The i-C₄H₁₀ chemical ionization spectrum of endo-2-norbornanol contains a much greater abundance of [M-H]⁺ ions than the i-C₄H₁₀ chemical ionization spectrum of exo-2-norbornanol. This difference presumably results from steric hindrance toward attack of the endo hydrogen.     

Natural Abundance 15N NMR by Dynamic Nuclear Polarization: Fast Analysis of Binding Sites of a Novel Amine‐Carboxyl‐Linked Immobilized Dirhodium Catalyst

A novel heterogeneous dirhodium catalyst has been synthesized. This stable catalyst is constructed from dirhodium acetate dimer (Rh₂(OAc)₄) units, which are covalently linked to amine‐ and carboxyl‐bifunctionalized mesoporous silica (SBA‐15?NH₂?COOH). It shows good efficiency in catalyzing the cyclopropanation reaction of styrene and ethyl diazoacetate (EDA) forming cis‐ and trans‐1‐ethoxycarbonyl‐2‐phenylcyclopropane. To characterize the structure of this catalyst and to confirm the successful immobilization, heteronuclear solid‐state NMR experiments have been performed. The high application potential of dynamic nuclear polarization (DNP) NMR for the analysis of binding sites in this novel catalyst is demonstrated. Signal‐enhanced ¹³C CP MAS and ¹⁵N CP MAS techniques have been employed to detect different carboxyl and amine binding sites in natural abundance on a fast time scale. The interpretation of the experimental chemical shift values for different binding sites has been corroborated by quantum chemical calculations on dirhodium model complexes.     

An Investigation of Lanthanum Coordination Compounds by Using Solid‐State 139La NMR Spectroscopy and Relativistic Density Functional Theory

Lanthanum‐139 NMR spectra of stationary samples of several solid La^III coordination compounds have been obtained at applied magnetic fields of 11.75 and 17.60 T. The breadth and shape of the ¹³⁹La NMR spectra of the central transition are dominated by the interaction between the ¹³⁹La nuclear quadrupole moment and the electric field gradient (EFG) at that nucleus; however, the influence of chemical‐shift anisotropy on the NMR spectra is non‐negligible for the majority of the compounds investigated. Analysis of the experimental NMR spectra reveals that the ¹³⁹La quadrupolar coupling constants (C_Q) range from 10.0 to 35.6 MHz, the spans of the chemical‐shift tensor (Ω) range from 50 to 260 ppm, and the isotropic chemical shifts (δ_iso) range from ?80 to 178 ppm. In general, there is a correlation between the magnitudes of C_Q and Ω, and δ_iso is shown to depend on the La coordination number. Magnetic‐shielding tensors, calculated by using relativistic zeroth‐order regular approximation density functional theory (ZORA‐DFT) and incorporating scalar only or scalar plus spin–orbit relativistic effects, qualitatively reproduce the experimental chemical‐shift tensors. In general, the inclusion of spin–orbit coupling yields results that are in better agreement with those from the experiment. The magnetic‐shielding calculations and experimentally determined Euler angles can be used to predict the orientation of the chemical‐shift and EFG tensors in the molecular frame. This study demonstrates that solid‐state ¹³⁹La NMR spectroscopy is a useful characterization method and can provide insight into the molecular structure of lanthanum coordination compounds.     

Applications of 95Mo NMR. 5—substituent effects in the 95Mo and 13C NMR spectra of benzyltricarbonyl(η5-cyclopentadienyl)molybdenum(II) derivatives

A systematic study has been made of the effects of substituent induced chemical shifts in [(η⁵-C₅H₅)(CO)₃Mo(CH₂C₆H₄R)] compounds. Both ⁹⁵Mo and ¹³C NMR shifts in the aromatic ring are reported. The (η⁵-C₅H₅)(CO)₃MoCH₂? group is a reasonably strong resonance donor (σ_R° = ?0.21) and weak inductive donor (σ_I = ?0.07). The molybdenum chemical shifts are extremely sensitive to the effects of distant substituents (range c. 40 ppm). Since the shift correlates well with substituent constants in this series, it is suggested that the chemical shift is controlled by the paramagnetic term for this spin 5/2 nucleus.     

The 19F NMR spectrum of cis-1,2-dichlorohexafluorocyclobutane

The ¹⁹F spectrum of cis-1,2-dichlorohexafluorocyclobutane has been fully analysed on the basis of an [ABX]₂ spin system, with initial treatment at an [AMX]₂ level. The chemical shift and coupling constants are presented, and the latter are discussed. Some comments are made on the spectrum of the trans isomer.