Chemical shift database

So if this all sounds a bit bleak, what s the good news Well, strangely, there is quite a lot. For a start, let s not forget that had the 13C nucleus been the predominant carbon isotope, the development of the whole NMR technique itself would have been held back massively and possibly even totally overlooked as proton spectra would have been too complex to interpret. Whimsical speculation aside, chemical shift prediction is far more reliable for 13C than it is for proton NMR and there are chemical shift databases available to help you that are actually very useful (see Chapter 14). This is because 13 C shifts are less prone to the effects of molecular anisotropy than proton shifts as carbon atoms are more internal to a molecule than the protons and also because as the carbon chemical shifts are spread across approximately 200 ppm of the field (as opposed to the approx. 13 ppm of the proton spectrum), the effects are proportionately less dramatic. This large range of chemical shifts also means that it is relatively unlikely that two 13C nuclei are exactly coincident, though it does happen. 

Advanced Chemistry Development Inc. has built a sizeable proton chemical shift database derived from published spectra (most commonly in CDCI3 solution). Their H NMR predictor programme accesses this database and allows the prediction of chemical shifts. Whilst this software takes account of geometry in calculating scalar couplings, in predicting chemical shifts it essentially treats the structure as planar. It would therefore seem doomed to failure. However, if closely related compounds, run at infinite dilution and in the same solvent, are present in the database, the conformation is implied and the results can be quite accurate. Of course, the results will not be reliable if sub-structures are not well represented within the database and the wide dispersion of errors (dependent on whether a compound is represented or not) can cause serious problems in structure confirmation (later). ACD are currently revising their strict adherence to HOSE codes for sub-structure identification and this will hopefully remove infrequent odd sub-structure selections made currently. 

ACD/Labs (www.acdlabs.com) markets several extensive NMR databases. The H database now exceeds 600,000 experimental chemical shifts and 110,000 coupling constants from 81,000 molecules, and that for 13C is based on more than 900,000 chemical shifts. Databases for 19F and 31P each have more than 20,000 chemical shifts. The databases are linked to programs that predict NMR spectra for given molecular structures and substructures. 

In addition to the published literature, a chemical shift database is being developed by Advanced Chemistry Development (AC D/Labs) that can be used interactively by an investigator both to predict chemical shifts for a molecule being investigated and to search the database by a multitude of parameters, including structure, substructure, and alphanumeric text values. This database is accessible in the NNMR software package offered by ACD/Labs and presently contains data on more than 8800 compounds with over 20 700 chemical shifts. Examples of the use of the NNMR database will be presented later in this chapter. 

Briefly, a nucleus in a magnetic field of 2.3488 T will typically resonate within 1 kHz of 100 MHz. Because of the response of the molecule s core and valence electrons to the magnetic field, the actual field at the nucleus will be slightly different, that is, it will be shifted from 2.3488 T, hence the label chemical shift , with the symbol d and in units of parts per million (ppm). Based on the asymmetric structure of 1-chloroethene, all three hydrogens will have slightly different chemical shifts, as shown in Fig. 7.2. For example, in 1-chloroethene, H has a chemical shift of 6.26 ppm, while for the analogous vinyl fluoride, the shift for the H is reduced to 6.17 ppm. On the basis of years of experience with NMR spectroscopy, chemical shift databases are available for H, Si, F, and most other... 

The databases which included the Jhh coupling and the H, and H(OH) chemical shift databases for contiguous polyols have been reported by Kishi and co-workers. The authors indicate that a stereochemical analysis based on three or two contiguous Jhh profiles is operationally simpler than one based on and H chemical shift profiles. 

Widmalm et al7 studied and C NMR chemical shifts assignment of mono-, di-, tri- and tetrasaccharides (totally 43 compounds) and applied them for NMR chemical shift predictions of oligosaccharides depicted in Fig. 1 using CASPER program. The CASPER (computer assisted spectrum evaluation of regular polysaccharides) software contains chemical shift database and empirical spectra simulation routine optimized for carbohydrates. The calculated chemical shifts are in good to excellent agreement with those from and C NMR experiments. 

A number of other software packages are available to predict NMR spectra. The use of large NMR spectral databases is the most popular approach it utilizes assigned chemical structures. In an advanced approach, parameters such as solvent information can be used to refine the accuracy of the prediction. A typical application works with tables of experimental chemical shifts from experimental NMR spectra. Each shift value is assigned to a specific structural fragment. The query structure is dissected into fragments that are compared with the fragments in the database. For each coincidence, the experimental chemical shift from the database is used to compose the final set of chemical shifts for the... 

Ab-initio calculations are particularly usefiil for the prediction of chemical shifts of unusual species". In this context unusual species" means chemical entities that are not frequently found in the available large databases of chemical shifts, e.g., charged intermediates of reactions, radicals, and structures containing elements other than H, C, O, N, S, P, halogens, and a few common metals. 

A useful empirical method for the prediction of chemical shifts and coupling constants relies on the information contained in databases of structures with the corresponding NMR data. Large databases with hundred-thousands of chemical shifts are commercially available and are linked to predictive systems, which basically rely on database searching [35], Protons are internally represented by their structural environments, usually their HOSE codes [9]. When a query structure is submitted, a search is performed to find the protons belonging to similar (overlapping) substructures. These are the protons with the same HOSE codes as the protons in the query molecule. The prediction of the chemical shift is calculated as the average chemical shift of the retrieved protons. 

In such tables, typical chemical shifts are assigned to standard structure fragments (e.g., protons in a benzene ring). Substituents in these blocks (e.g., substituents in ortho, meta, or para positions) are assumed to make independent additive contributions to the chemical shift. These additive contributions are listed in a second series of tables. Once the tables are defined, the method is easy to implement, does not require databases, and is extremely fast. Predictions for a molecule with 50 atoms can be made in less than a second. On the other hand, it requires that the parent structure and the substituents are tabulated, and it considers no interaction... 

A portion of the PV A database is shown in Figure 3. Boxed entries indicate required input from the user. In this case, a Bernoullian model is the most likely choice. The program completes the database by calculating a chemical shift window and the coefficients from Equation 1 for each peak. 

All chemical shift data presented in this book come either from the primary literature or from spectra obtained in the author s laboratory. All spectra actually depicted in the book derive from spectra obtained by the author at the University of Florida. All data from the literature were obtained via searches using MDL Crossfire Commander or SciFinder Scholar. Persons interested in accessing such primary literature can do so readily via these databases by simply searching for the specific compound mentioned in the text. 

Regarding the multitude of NMR chemical shifts of specific compounds that are provided within the text, references for chemical shifts of individual compounds for the most part will not be cited. It is assumed that if such references are required, the reader can find them by a quick search using either MDL Crossfire Commander or SciFinder Scholar. The author found MDL Crossfire Commander the superior database for locating specific NMR data. 

So to a large extent, 1-D 13C NMR interpretation is a case of matching observed singlets to predicted chemical shifts. These predictions can be made by reference to one of the commercially available databases that we ve mentioned, or it can be done the hard way - by a combination of looking up reference spectra of relevant analogues and using tables to predict the shifts of specific parts of your molecule (e.g., aromatic carbons). We have included some useful 13C shift data at the end of the chapter but it is by necessity, very limited. 

Modem carbon prediction software has hundreds of thousands of chemical structures to call on (Bremser had about 10000 when he started). The more structures you have, the better the chance that something similar to your structure will be in the database - and the better the quality of the chemical shift... 

Despite having been the earliest attempted prediction, proton prediction remains relatively poor. The reasons for this have been alluded to earlier but to summarise the proton chemical shift is often highly dependant on through-space effects (anisotropy) and has a very small distribution. There are four main commercial approaches to proton prediction currently Incremental parameters, HOSE code databases, semi-empirical and cib initio methods. 

ACD/Labs have an extensive database which uses this approach. This approach works well except for anisotropic groups. Unlike carbon prediction this can have a massive effect on the chemical shift values and so can give rise to big errors in prediction, even for structural fragments that are well represented in... 

Vast tabulations of 13C chemical shift data have been assembled in computer searchable form. These databases form the basis for 13C chemical shift prediction algorithms. For the most part, carbon chemical shifts can be calculated using what is referred to as a Hierarchically Ordered Spherical Environment (HOSE) code approach [28]. To calculate a given carbon s chemical shift, the influence of each successive spherical shell is applied to the starting chemical shift for that carbon to calculate its overall chemical shift. Typically, programs will calculate shifts for 3 or 4 layers, beyond which the effects of most substituents are negligible. The spherical layers surrounding the 23-position of strychnine are shown in Fig. 10.8. 

A validated database of compounds and associated chemical shifts. Experience shows significant levels of inaccuracy (both in structure and assignment) even in published data. 

Using databases or tables of SCS to predict proton chemical shifts, only through-bond effects are effectively considered, and a typical r.m.s. difference between calculated and experimental shifts is 0.3 ppm. This is a lower value than for shifts, but this is a much higher proportion of the chemical shift range (3 vs. 0.75%). 

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