Stereochemical substructure codes for 13C spectral analysis

Computer programs for encoding canonical representations of stereochemical substructural environments are presented. Applications of these substructure codes in the study of relationships between molecular structure and chemical shifts observed in ¹³C NMR spectra are described, using natural products as examples. The utility of the codes for the detection of erroneous spectral assignment is illustrated.     

CAST/CNMR: highly accurate C NMR chemical shift prediction system considering stereochemistry

Accurate, practical prediction of ¹³C NMR chemical shifts has been achieved with a new system, CAST/CNMR, taking account of stereochemistry. The CAST/CNMR system has solved the critical problem of the accurate distinction of differences and similarities in stereochemical structures around a specific carbon, which has not yet been achieved by any other database-oriented system for prediction of ¹³C NMR chemical shifts. CAST/CNMR uses a three-dimensional structural database together with a ¹³C NMR spectral database. Absolute/relative configurational and conformational structural information are described by the CAST (CAnonical-representation of STereochemistry) coding method. This paper provides an overview of the CAST/CNMR system, and describes its application to two natural products as examples.     

Differentiation of diastereoisomeric terpenoid alcohols by electron impact and negative ion chemical ionization associated with collision-induced dissociation. A fourier transform ion cyclotron resonance study

Electron impact ionization-collision-induced dissociation (EI-CID) and negative ion chemical ionization-collision-induced dissociation (NICI-CID) experiments have been performed on the molecular or quasi-molecular ions (M^+· or [M - H]^?) of series of terpenoid alcohols, using a Fourier transform ion cyclotron resonance spectrometer. These terpenes belong to the p-menthane family and bear a hydroxyl group in various positions relative to the isopropyl or isopropenyl substituent (positional or stereochemical isomers). In the case of positional isomers, different CID spectra were always obtained. Within a given diastereoisomeric series, stereochemical differences were also observed in both NICI-CID and EI-CID experiments.     

Computer generation of chemical structures from known fragments

The interactive generation of chemical structures from given fragments is described and discussed. It is implemented as a part of our expert system CARBON, based on C-13 NMR spectra. As it is designed, this program can also be a useful tool in the structure elucidation process when information on parts of the structure is obtained by other means (IR, mass and other spectrometries, chemical analysis, other relevant information). The topological characteristics of candidate fragments are first chosen interactively and then the elements are connected in all topologically possible ways. In the following step, the topological building blocks are substituted by chemical structural fragments resulting in a set of all chemical structures consistent with the input information.     

Computer-aided elucidation of structures by carbon-13 nuclear magnetic resonance The DARC-EPIOS Method: Characterization of Ordered Substructures by Correlating the Chemical Shifts of Their Bonded Carbon Atoms

A reference substructure (SS) for which all spectral information (I) associated with each carbon atom is expressed as a function of the molecular environment is proposed. This information is expressed by topological relations, within this substructure, for which the spectral responses of its “bonded atoms” are linearly related to external alkyl effects. A correlation space (SS/I) is built with these topological relations (1–4 per carbon substructure). The resolving capacity of this SS/I space is greatly enhanced by introducing, in addition to all the reference substructures, some functions such as heteroatoms, cyclic structures, and stereochemical situations. The action of these functions is estimated by a statistical study of a large population of compounds from the DARC-PLURIDATA ¹³C-n.m.r. bank. This work introduces the notion of multiatom-centered substructure/multi-chemical shift relations, the discriminating ability of which compares very favorably to that of the notion of atom-centered substructure/monochemical shift relations. The generic reference subtructure defined as ELCO_b with its multichemical shifts constitutes a simple structural whole which is useful for critical improvement of the experimental reference data (distribution of spectral information and medium effects) and has proved to be excellent for the elucidation of new structures.     

Predicting bondons by Goldstone mechanism with chemical topological indices

The Goldstone symmetry breaking algorithm is applied on ?² and ?⁴ chemical field contributions weighted, respectively, by the sphericity and extreme‐sphericity topological indices to provide for stable chemical bonding in the high temperature regime, the typical mass for the bondon, and the associated quantum boson. The method is applied to a representative series of polycyclic aromatic hydrocarbons providing an aromaticity hierarchy comparable with the scale‐based on the chemical hardness; present calculations on the bondonic mass place the physical existence of that bosonic‐bondonic quantum particle in the range of a few GeV and 10^?22 s, as typical for negatively charged massive bosons. © 2014 Wiley Periodicals, Inc.     

Values below detection limit in compositional chemical data

Samples representing part of a whole, usually called compositional data in statistics, are commonplace in analytical chemistry—say chemical data in percentage, ppm, or μg g⁻¹. Their distinctive feature is that there is an inherent relationship between all the analytes constituting a chemical sample as they only convey relative information. Some compositional data analysis principles and the log-ratio based methodology are outlined here in practical terms. Besides, one often finds that some analytes are not present in sufficient concentration in a sample to allow the measuring instruments to effectively detect them. These non-detects are usually labelled as “<DL” (less-thans) in the data set, indicating that the values are below known detection limits. Many data analysis techniques require complete data sets. Thus, there is a need of sensible replacement strategies for less-thans. The peculiar nature of compositional data determines any data analysis and demands for a specialised treatment of less-thans that, unfortunately, is not usually covered in chemometrics. Some well-founded statistical methods are revisited in this paper aiming to prevent practitioners from relying on popular but untrustworthy approaches. A new proposal to estimate less-thans combining a log-normal probability model and a multiplicative modification of the samples is also introduced. Their performance is illustrated and compared on a real data set, and guidelines are provided for practitioners. Matlab and R code implementing the methods are made available for the reader.     

ChemNetworks: A complex network analysis tool for chemical systems

Many intermolecular chemical interactions persist across length and timescales and can be considered to form a “network” or “graph.” Obvious examples include the hydrogen bond networks formed by polar solvents such as water or alcohols. In fact, there are many similarities between intermolecular chemical networks like those formed by hydrogen bonding and the complex and distributed networks found in computer science. Contemporary network analyses are able to dissect the complex local and global changes that occur within the network over multiple time and length scales. This work discusses the ChemNetworks software, whose purpose is to process Cartesian coordinates of chemical systems into a network/graph formalism and apply topological network analyses that include network neighborhood, the determination of geodesic paths, the degree census, direct structural searches, and the distribution of defect states of network. These properties can help to understand the network patterns and organization that may influence physical properties and chemical reactivity. The focus of ChemNetworks is to quantitatively describe intermolecular chemical networks of entire systems at both the local and global levels and as a function of time. The code is highly general, capable of converting a wide variety of systems into a chemical network formalism, including complex solutions, liquid interfaces, or even self‐assemblies. © 2013 Wiley Periodicals, Inc.     

The alkali cation effect on the 1H NMR chemical shifts of the indenyl carbanion

The complex character of the temperature dependence of the ¹H NMR chemical shifts of indenyl-lithium and -sodium in dimethoxyethane is explained. It is shown that the cation causes a polarisation of the C? H bonds and thus influences the proton shifts of the anion, both directly by its electric field along the bonds (the direct effect) and indirectly via its effect on the π-electron distribution (the indirect effect). The indirect effect is inferred from ¹³C NMR chemical shift data. By subtracting the temperature dependent contribution of the indirect effect from the experimental ¹H data, the direct effect is visualised. It appears that information on ion paris obtained by ¹H and ¹³C NMR on the one hand and optical spectroscopy on the other hand is complementary. Apparently, aggregation of ion pairs does not seriously affect the chemical shift data.     

Conformational analysis of dibenzo[a,e]cyclooctadiene and three related heterocyclic compounds

A theoretical B3LYP/6-311++G(d,p) study of four derivatives of cyclooctadiene bearing two aromatic or heteroaromatic rings is reported. The conformational analysis reproduces well the experimental results (minima and transition states). The GIAO calculated ¹H and ¹³C chemical shifts proved useful in solving some stereochemical questions.

     

Stereospecific adduct ion formation in the chemical ionization mass spectra of E- and Z-1,2,3-triaryl-2-propen-1-ones

Stereospecific adduct ion formation has been observed in the chemical ionization mass spectra (positive and negative) of certain E- and Z-1,2,3-triaryl-2-propen-1-ones. The Z isomers are found to give higher relative abundances of adduct ions than the E isomers. This has been interpreted in terms of the differences in the proton affinities of the isomers originating from their different degrees of enone resonance. Halide ion (CI^? and Br^?) attachment spectra of these compounds also show stereochemical differences in the relative abundances of [M]^?˙ and [M+halide]^? ions, though the effect is not as pronounced as in the case of the positive ion spectra.     

Inverted chemical force microscopy: following interfacial reactions on the nanometer scale

Atomic force microscopy (AFM) with chemical specificity using chemically modified AFM probes, so-called chemical force microscopy, was applied to study surface chemical reactions on the nanometer scale. To overcome the typical limitations of conventional AFM in following reactions in real-time, i.e. slow data acquisition, as well as thermal and instrumental drifts, we have introduced a new approach, named inverted chemical force microscopy (iCFM). In iCFM the reactants are immobilized on the AFM tip rather than on the substrate. The chemical reactions take place at the surface of the tip and are probed in real-time by force-displacement measurements on an inert octadecanethiol-covered Au substrate. The reactions studied were the hydrolysis and aminolysis of 11,11^′-dithiobis(N-hydroxysuccinimidylundecanoate) (NHS-C₁₀). By iCFM intermolecular interactions and hence reaction kinetics can be quantitatively studied on the level of ∼10-100 molecules. In particular, our iCFM data showed that the aminolysis reaction with n-butylamine on SAMs of NHS-C₁₀ is a spatially heterogeneous reaction. In addition, information about the defect density of reactive SAMs was obtained.     

Computer generation of Hadamard matrices

We develop a computer code that uses elegant bit-manipulation techniques for matrix multiplication and thus facilitates exhaustive generation of Skew-Hadamard matrices. Hadamard matrices are useful in spectroscopic applications (Hadamard transform spectroscopy) and in balanced chemical designs. Application of our code yields several Skew-Hadamard matrices up to order 100 × 100, although the combinatorial complexity of exhaustive generation increases exponentially. Our bit-manipulation-based codes took 124 h of CPU time to perform 7.79344 × 10¹¹ matrix multiplications on an IBM RS 6000/560 system to generate all 100 × 100 matrices. This amounts to 5.7 × 10^?7 s of CPU time per matrix multiplication. © 1993 John Wiley & Sons, Inc.     

Relative molecular mass information from aliphatic nitro compounds: A chemical ionization study

The mass spectra of a number of aliphatic nitro compounds have been studied using electron Ionization (EI) and a variety of chemical Ionization (CI) techniques in attempts to obtain relative molecular mass information. The use of positive ion ammonia chemical Ionization techniques gave very satisfactory results, providing abundant [M + NH4]⁺ ions, not only from both primary and secondary nitro compounds, but also from the much more labile tertiary nitro compounds. However, the use of methane and isobutane positive ion CI or EI conditions resulted in facile fragmentation with little relative molecular mass information being made available. Negative ion CI using methane, isobutane or ammonia as moderating gases all gave abundant [M ? 1]^? ions with primary and secondary nitro compounds but at much reduced sensitivity.     

Lossless compression of chemical fingerprints using integer entropy codes improves storage and retrieval

Many modern chemoinformatics systems for small molecules rely on large fingerprint vector representations, where the components of the vector record the presence or number of occurrences in the molecular graphs of particular combinatorial features, such as labeled paths or labeled trees. These large fingerprint vectors are often compressed to much shorter fingerprint vectors using a lossy compression scheme based on a simple modulo procedure. Here, we combine statistical models of fingerprints with integer entropy codes, such as Golomb and Elias codes, to encode the indices or the run lengths of the fingerprints. After reordering the fingerprint components by decreasing frequency order, the indices are monotone-increasing and the run lengths are quasi-monotone-increasing, and both exhibit power-law distribution trends. We take advantage of these statistical properties to derive new efficient, lossless, compression algorithms for monotone integer sequences: monotone value (MOV) coding and monotone length (MOL) coding. In contrast to lossy systems that use 1024 or more bits of storage per molecule, we can achieve lossless compression of long chemical fingerprints based on circular substructures in slightly over 300 bits per molecule, close to the Shannon entropy limit, using a MOL Elias Gamma code for run lengths. The improvement in storage comes at a modest computational cost. Furthermore, because the compression is lossless, uncompressed similarity (e.g., Tanimoto) between molecules can be computed exactly from their compressed representations, leading to significant improvements in retrival performance, as shown on six benchmark data sets of druglike molecules.     

Crystallographic and first-principles density functional theory study on the structure,noncovalent interactions,and chemical reactivity of 1,5-benzodiazepin-2-ones derivatives

The present work arose out of a desire to fundamentally understand the molecular geometry, weak interactions, electron density delocalization, and chemical reactivity features of 1,5-benzodiazepines-containing family. Herein, a complete X-ray crystallographic study, supported by trustworthy sets of computational approaches, has been reported for two organic crystals. Quantifying intramolecular and intermolecular interactions by Hirshfeld-Becke surfaces analysis conjointly with noncovalent interaction-reduced density gradient topological study revealed that supramolecular assemblies are stabilized by N-H ^… O (inter) and O-H ^… N (intra) hydrogen bonds, Cg ^… Cg (π ^… π) and C-H(O) ^… π intercontacts, as well as Van der Waals interactions and steric effects. The long-range-corrected functional wB97XD, which uses Grimme's D2 dispersion model, seems to be just right for our systems. The quantum theory of atoms in molecules analysis confirms that both significant O1-H1…N1 and N2-H2A…O2 H-bonds are weak and electrostatic in nature. Furthermore, global reactivity indices computed via the conceptual density functional theory framework allows these molecules to be classified as moderate electrophiles and marginal nucleophiles. The active sites favorable for nucleophilic/electrophilic attacks were also predicted based on local Parr functions. Finally, a comparative evaluation on the aromaticity character and π-π stacking ability has been done for different (pseudo) rings.     

Is the 31P chemical shift anisotropy of aluminophosphates a useful parameter for NMR crystallography?

The ³¹P chemical shift anisotropy (CSA) offers a potential source of new information to help determine the structures of aluminophosphate (AlPO) framework materials. We investigate how to measure the CSAs, which are small (span of ~20–30 ppm) for AlPOs, demonstrating the need for CSA-amplification experiments (often in conjunction with ²⁷Al and/or ¹H decoupling) at high magnetic field (20.0 T) to obtain accurate values. We show that the most shielded component of the chemical shift tensor, δ₃₃, is related to the length of the shortest P─O bond, whereas the more deshielded components, δ₁₁ and δ₂₂ can be related more readily to the mean P─O bond lengths and P─O─Al angles. Using the case of Mg-doped STA-2 as an example, the CSA is shown to be much larger for P(OAl)_4–n(OMg)_n environments, primarily owing to a much shorter P─O(Mg) bond affecting δ₃₃, however, because the mean P─O bond lengths and P─O─T (T = Al, Mg) bond angles do not change significantly between P(OAl)₄ and P(OAl)_4–n(OMg)_n sites, the isotropic chemical shifts for these species are similar, leading to overlapped spectral lines. When the CSA information is included, spectral assignment becomes unambiguous, therefore, although the specialist conditions required might preclude the routine measurement of ³¹P CSAs in AlPOs, in some cases (particularly doped materials), the experiments can still provide valuable additional information for spectral assignment.     

The increment scheme for the prediction of13C NMR chemical shifts in polychlorinated dibenzo-p-dioxins

A topological method for the calculation of¹³C NMR chemical shifts was developed for polychlorinated dibenzo-p-dioxins (PCDD). Based on previous results for polychlorinated benzenes and polyhydroxybenzenes, the collective influence of the substituents on carbon chemical shifts is presented as the sum of two-particle increments. The increments only of two new monosubstituted graphs have to be added to those known for PCDD spectra: 1-Cl-DD and 2-Cl-DD. All structural situations in the¹³C NMR chemical shifts of the whole class of 75 PCDD can be covered with a few model compounds. The coefficients of the increment scheme are independent of the change of CDCl₃ for acetone-d₆, so it may be a new reliable criterion for recognizing PCDD by¹³C NMR, in spite of the close resemblance of NMR spectra of aromatic compounds.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 280–284, February, 1995.