13C nuclear magnetic resonance data of bile acid derivatives

The 13C-NMR spectra of well over 100 bile acid derivatives have been analyzed and summarized. A diagnostic gamma-oxygen shielding effect has been identified.     

Construction of a data base for cobalt-59 nuclear magnetic resonance spectrometry

The TOOL-IR. PDB and COOD systems are compared for the construction of data bases for ⁵⁹Co-n.m.r. bibliographic and spectral data. The spectral data used are the chemical shifts from several different standards, and the line widths and coupling constants (if present). The PDB system is effective for storage and retrieval of bibliographic data, but the COOD system is better for the retrieval of spectral data, and for combination of data files on literature and chemical shifts.     

SPECA: a program for the calculation of thermodynamic equilibrium constants from spectrophotometric data

A computer program called SPECA and written in compiled BASIC (Microsoft QuickBasic Ver. 4.5) has been written for the calculation of thermodynamic constants in solution equilibria studies from spectrophotometric measurements. In order to calculate the thermodynamic constants it is necessary to introduce different theories to estimate the activity coefficients of the system involved under investigation. In this version of the program the equations proposed in the models of Debye-Hückel. Specific Interaction Theory (SIT) or the Modified's Bromley Theory can be chosen. To achieve its purpose, the program uses absorbance and activity or free concentration data of one of the components, normally H(+), and it is not limited with respect to the number of components that can be studied. Minimization of the error square sum in the absorbance, which can be absolute or relative, is carried out using the Levenberg-Marquardt-Nash algorithm at three different levels: equilibrium constants in the first level, molar absorptivities in the second and interaction coefficients in the third for those systems using the SIT or the Modified Bromley's Theories.     

Insights into partially folded or unfolded States of metalloproteins from nuclear magnetic resonance

Nuclear magnetic resonance (NMR) provides detailed insights into the conformational features of unfolded and partially folded proteins. In the case of metalloproteins, special attention should be devoted to the characterization of the properties of the metal binding sites, and specific approaches need to be developed depending on the nature of the metal ion and its coordination environment. At the same time, metal-based NMR parameters may help in getting a better picture of the average structural properties of the metalloprotein. A critical evaluation of the limits of applicability of paramagnetic effects for solution structure determination in partially folded or unfolded proteins is presented. The coupling between NMR characterization of structure and dynamic of the polypeptide chain and of the metal environment provides insights into the stabilizing role of metal ions in metalloproteins. The overall approach is illustrated for some case examples of increasing flexibility obtained far from native conditions for cytochrome c and superoxide dismutase, two metalloproteins that have been extensively studied in our lab and whose misfolded forms may be relevant for important biological processes.     

Spectra–structure relationships in carbon-13 nuclear magnetic resonance spectroscopy. Results from a large data base

A link between a substructure searching system and a ¹³C NMR data base has been established and permits the retrieval and examination of the chemical shifts associated with specific substructures. The means by which these searches are accomplished is described and the results from the searches are presented and discussed. The system is interactive, and can be used to locate in the data base the chemical shifts of carbon atoms in precisely defined environments. Alternatively, it may be used to learn the range of the chemical shifts possessed by particular types of carbon atoms, such as N-methyl or O-methyl carbons.     

Decomposition of nuclear magnetic resonance spin-spin coupling constants into active and passive orbital contributions

The theory of the J-OC-PSP (decomposition of J into orbital contributions using orbital currents and partial spin polarization) method is derived to distinguish between the role of active, passive, and frozen orbitals on the nuclear magnetic resonance (NMR) spin-spin coupling mechanism. Application of J-OC-PSP to the NMR spin-spin coupling constants of ethylene, which are calculated using coupled perturbed density functional theory in connection with the B3LYP hybrid functional and a [7s,6p,2d/4s,2p] basis set, reveal that the well-known pi mechanism for Fermi contact (FC) spin coupling is based on passive pi orbital contributions. The pi orbitals contribute to the spin polarization of the sigma orbitals at the coupling nuclei by mediating spin information between sigma orbitals (spin-transport mechanism) or by increasing the spin information of a sigma orbital by an echo effect. The calculated FC(pi) value of the SSCC (1)J(CC) of ethylene is 4.5 Hz and by this clearly smaller than previously assumed.     

Reliability of association constants of 1:1 molecular complexes from spectrophotometric data

Some basic factors affecting the reliability of K (association constant) and ? (molecular extinction coefficient) estimates for 1:1 molecular complexes are studied. To accomplish this, the error matrix is examined and a new variable G=K^?1((a+b+K^?1)2?4ab)^{?$\text{1}\text{2}$} (where a and b are the concentrations of the reagents) is introduced. Whenever G has the same value for all the experimental points, K and ? are undetermined. A great dispersion of G values, on the contrary, contributes to more reliable estimates. The variable G has in fact the same role as the independent variable in a linear relationship; therefore the problem of the optimal choice of experimental points is reduced to one of a simple linear regression.     

Determination of acid dissociation constants of histidine-containing peptides by proton magnetic resonance spectroscopy

The acid dissociation constant of the imidazolium ring of the decapeptide luliberin has been determined by ¹H NMR-followed titration in D₂O. The normal procedure for the analysis of the titration curve, i.e. direct use of the Henderson-Haselbalch equation, is still applicable in this case, but for more complex peptides a modified calculation procedure is proposed. Results obtained when both methods were applied to luliberin are compared. The influence of D₂O when used as the solvent in this type of determination has been studied using N^α-acetyl-L -histidine methyl ester as a model compound. The difference between the acid dissociation constant of this molecule determined in H₂O and in D₂O implies that a correction of ?.25 unit is needed for those pK_a values calculated by plotting the chemical shifts in D₂O vs the apparent pH meter readings. The pK_a found for N^α-acetyl-L-histidine methyl ester, 6.30 ± 0.04, can be taken as a standard value for histidine-containing peptides.     

Self-consistent perturbation-INDO calculations of nuclear magnetic resonance carbon–carbon coupling constants for methylcycloalkanes

One bond ¹³C,¹³C coupling constants have been calculated for some methylcycloalkanes, as well as for 2-methylbutane, using the self-consistent perturbation theory as formulated by Blizzard and Santry at the INDO (intermediate neglect of differential overlap) level of approximation. Together with previously published experimental data, the results can be interpreted satisfactorily on the basis of the Walsh model for cyclopropane and the known s character relationship ¹J(¹³C¹³C) = 575·s(i)· s(j).     

Phosphorus-31 nuclear magnetic resonance chemical shifts of phosphoric acid derivatives

(31)P nuclear magnetic resonance chemical shifts of alkyi and alkylaryl phosphates, condensed phosphates, phosphoric arids and their salts, are reported. These are listed by classes of compounds so that relationships between chemical shifts and the substituent groups on phosphorus atoms can be recognized. These relationships are useful for qualitative identification of the specific compounds listed and of related compounds by extrapolation.     

Parity nonconservation contribution to the nuclear magnetic resonance shielding constants of chiral molecules: a four-component relativistic study

A systematic four-component relativistic study of the parity nonconservation (PNC) contribution to the (isotropic) NMR shielding constants of chiral molecules is presented for the P enantiomers of the series H(2)X(2) (X=(17)O,(33)S,(77)Se,(125)Te,(209)Po). The PNC contributions are obtained within a linear response approach at the Hartree-Fock level. A careful design of the basis sets is necessary. The four-component relativistic results based on the Dirac-Coulomb Hamiltonian are compared with the nonrelativistic Levy-Leblond results and those obtained by the spin-free modified Dirac Hamiltonian. The calculations confirm the nonrelativistic scaling law Z(2.4) of the PNC contribution with respect to nuclear charge Z. However, the calculations also show that the overall scaling is significantly modified by relativistic effects. The scalar relativistic effect scales as Z(4.7) for the selected set of molecules, whereas the spin-orbit effect, of opposite sign, scales better than Z(6) and completely dominates the PNC contribution for the heaviest elements. This opens up the intriguing possibility of the experimental observation of PNC effects on NMR parameters of molecules containing heavy atoms. The presented formalism is expected to be valuable in assisting the search for suitable candidate molecules.     

Determination of the stereochemistry of natural products from nuclear magnetic resonance data by constrained molecular dynamics

We have developed a molecular modeling procedure to determine the relative configuration of a chiral molecule from nuclear magnetic resonance (NMR) data. Our procedure uses constrained molecular mechanics, and the constraints are interproton distances derived from the experimental nuclear Overhauser enhancement (NOE) data. The main feature is a period of high-temperature dynamics in which frequent inversions occur at most chiral sites. This allows the distance constraints to guide the molecule into configurations consistent with the NOE data. For molecules with complex ring systems, high-temperature dynamics alone may fail to invert certain chiral centers with sufficient frequency. We have countered this by allowing as an option additional inversions of selected chiral centers. The procedure tested successfully on organic molecules of known stereochemistry, with 5 to 17 chiral centers, provided that the number of available constraints was at least twice the number of chiral centers. The procedure is tolerant of large errors in the estimated interproton distances and is reasonably rapid. For a series of sugars, the time required increases less than quadratically with the number of atoms. © 1996 by John Wiley & Sons, Inc.     

Multiwavelength spectrophotometric determination of acid dissociation constants Part IV. Water-insoluble pyridine derivatives

A multiwavelength spectrophotometric (WApH) titration method for determination of acid dissociation constants (pK(a) values) of ionizable compounds developed previously was applied in the case of pyridine derivatives of pharmaceutical interest. Specifically, UV absorption spectra of the drug solution are acquired in the course of a pH-metric titration using an optical device based on a fibre optics dip probe, a light source and a diode array detector. Target factor analysis was applied to deduce the pK(a) values from the spectral data recorded at different pH. Using this technique, the pK(a) values of six pyridine derivatives were determined successfully. It was demonstrated that the WApH technique in this case outperforms conventional pH-metric methods with respect to the measurement of pK(a) values of the sparingly water soluble samples reported in this study.     

General equation for determining the dissociation constants of polyprotic acids and bases from additive properties. Part II. Applications

Dissociation constants of some polyprotic acids and bases are determined from spectrophotometric and reversed-phase high performance liquid chromatographic data. A general equation relating additive properties of acids and bases to the pH of the solution is used for this purpose. The method is tested by applying it to the calculation of overlapping pK_as without the prerequisite of measuring the limiting values of the property for the individual species that result from the dissociation of the solute. The possibility of applying the same method to hyperpolarizability measurements is pointed out, and a procedure, based on the general equation, for obtaining the activity coefficients of the ionic species as a function of the ionic strength is also suggested.