Sometimes surfing the WWW can be as productive as it is fun. Last spring, while searching NMR web sites, I came across a series of links that I followed to the home page of Advanced Chemistry Development Inc. Several of their software packages caught my eye: a free chemistry drawing package and a pair of programs for predicting ¹H and ¹³C NMR spectra, which come bundled with a more complete chemistry drawing package. Despite my initial low expectations, I downloaded and installed this software and was pleasantly surprised by both packages.

Advanced Chemistry Development Inc., ACD, was formed "by a small group of independently minded young post-doctoral researchers working together at Moscow State University" in 1990; in 1994 they were incorporated (141 Adelaide St. West, Suite 1501, Toronto, ON M5H 3L5 Canada). Demonstration versions of their software are available for download from their web site (http://www.acdlabs.com) and on CD (inquire at info@acdlabs.com). Their chemistry drawing package, ACD/ChemSketch, is the common graphical user interface for their other software packages that interactively predict boiling points, partition coefficients, IUPAC names, ¹³C NMR spectra, and ¹H NMR spectra for user-defined structures. In this review, I discuss version 2.0 of their ChemSketch, CNMR, and HNMR software. They regularly update their products, so new versions with enhanced features, including web-based multi-platform client/server versions, probably will be available by the time you read this review.

The ChemSketch chemistry drawing package comes in two versions. ChemSketch 1.0 is a freeware program that lacks some of the features of the commercial ChemSketch 2.0 product. Nevertheless, this freeware product is broadly similar in functionality and ease of use to the popular chemistry drawing programs that I have used previously (ChemDraw and ChemWindows/ChemIntosh, from Cambridge Scientific Computing Inc. and SoftShell International, Ltd., respectively). It has all the standard drawing tools for flat and perspective drawings of organic and inorganic molecules. Also included are useful tools that quickly add substructure fragments from ACD templates (e.g., amino acid residues, nucleotides, functional groups, common protecting groups, rings, and chains) or from user-defined templates at the push of a button; tools that calculate molecular formulas, molecular weights, and percent composition as you draw the structure; and the "clean structure" button, which converts all the bond lengths and angles in your structure to standard values. Given the fact that ACD ChemSketch 1.0 is free, I think it is the best package for use by students, chemistry computer labs, and chemists on a budget.

The commercial ACD drawing package is called ChemSketch 2.0. It comes bundled with three other programs (ACD/Tautomers, ACD/Dictionary, and ACD/3D) with which it is seamlessly integrated. ChemSketch 2.0 includes all the functions of the freeware version. In addition, it contains a more comprehensive list of predefined substructure templates, including ones for sugars, heterocyclics, aromatics, and lab glassware. Version 2.0 also calculates the refractive index, molar volume, and density for compounds as you draw them. The bundled Tautomers module checks your drawings for likely tautomeric forms. The useful Dictionary module includes over 50,000 chemical names and structures as well as searchable information on the biological activities and enzyme inhibition properties of these. The 3D module is particularly useful. It converts 2-dimensional drawings into 3-dimensional wire frame structures using a modified molecular mechanics approach, and these pictures can be rotated and moved in three dimensions. ChemSketch 2.0 is reminiscent of the ChemDraw/Chem3D combination in terms of its features, but its faster structure minimization and additional features (e.g., its Dictionary and Tautomer components) make it preferable for many applications. However, it currently lacks the ability to represent the output in non-wire frame forms (e.g., ball-and-stick or CPK space-filling representations). The people at ACD could easily fix this significant and inexplicable weakness in their software by allowing one to save files in either the proprietary ACD format (*.sk2), which is the only choice now, or in a standard file format (e.g., the *.pdb, *.msv, or *.mdl formats). Alternatively, they could supply a file conversion utility to do this transformation. These other file formats are readable by several excellent freeware structure viewing packages. Two particularly good examples are the WebLab viewer (available from Molecular Simulations Inc. at http://www.msi.com) or the Chemscape Chime audiovisual plug-in for web browsers (available from MDL Information Systems at http://www.mdli.com).

The ACD/HNMR 2.0 and ACD/CNMR 2.0 NMR spectra prediction packages work similarly. Both come bundled with ACD/ChemSketch 2.0, which acts as their graphical user interface. To use them, one draws the molecule of interest with the ChemSketch 2.0 program and then clicks a button on the bottom of the window to calculate either the ¹H or the ¹³C NMR spectrum. These spectra are calculated by comparing their structural fragments with those in large spectroscopic data bases (from ¹³C chemical shifts for over 35,000 compounds and ¹H chemical shifts and coupling constants for over 44,000 compounds). For structures that are in the data base, the software uses the tabulated data to generate spectra. For new structures, the software displays not only the calculated spectra but also confidence limits for the calculated values, and it warns you if it can't make a reliable prediction. ACD says that its NMR package predicts spectra with an average error of ± 3 ppm. In my experience, both the HNMR package and the CNMR package do an excellent job of predicting the spectra for typical organic compounds, such as those routinely employed in sophomore organic chemistry. As one would expect, for more complex compounds that are more poorly represented in their data base (e.g., sugar derivatives, organometallics, and cyclophanes), the predictions are less reliable. When used for teaching, comparison of the experimental data for such species with the differing results of the calculations can be an interesting exercise, especially if one asks students to rationalize such differences in terms of fundamental phenomena such as ring currents or steric effects. For research purposes, users can add their own assigned spectra to the data base to train the software to predict the spectra of their particular classes of compounds more accurately.

In addition to spectra, the ACD NMR software can also display tables of chemical shifts and, for ¹H spectra, coupling constants. The ¹³C NMR spectra can be displayed as ¹H-coupled or ¹H-decoupled spectra, as off resonance decoupled (SFORD) spectra, as J-modulated (APT) spectra, and as CH₃, CH₂, CH, and C edited (DEPT) sub-spectra. Coupling constants to heteronuclei such as ¹⁹F and ³¹P are also calculated and displayed. The ¹H NMR spectra can be displayed as conventional spectra or as double resonance (decoupled) spectra, and there is a good spin simulator so users can model their own spin systems. Both packages include the option of using discrete or realistic lines (with user-definable line widths), variable field strengths, integral curves, etc. The most useful feature of these packages is that they are fully interactive. That is, if you touch the cursor to an atom on the drawing, its peak in the spectrum and its entries in the tables are highlighted and vice versa.

Overall, this is one of the most powerful and easy to use software packages I've seen. I have used it with students from my sophomore organic chemistry class, a senior level organic analysis course, a professional development course for high school chemistry teachers, and for one-on-one graduate student training. The students were universally enthusiastic about the package. Indeed, the high school chemistry teachers expressed interest in using this software to illustrate concepts of structure and bonding. The interactive nature of the packages along with the quick feedback they provide seems to dramatically flatten the learning curve for the use of NMR spectroscopy in structure determination. Indeed, because of the speed and interactivity with which spectra can be calculated from molecular drawings it also can dramatically speed the assignment of spectra even for experienced NMR users. As with other Windows programs, the calculated drawings or spectra can be printed from the ACD programs themselves or copied into the clipboard and pasted into other programs such as Microsoft Word.

These software packages come bundled with Lotus ScreenCam 96 presentations that do an excellent job of introducing beginners to the use of this software via short (about 5-minute) audiovisual demonstrations. These, along with the usual on-screen help and tip files, do a good job of training new users. A complete printed or printable (a postscript file) manual, however, is required for more advanced users to get the most out of these sophisticated software packages. In addition, many users, including myself, prefer having a printed manual available that they can take with them to read on the bus, at home in the evening, while proctoring exams, etc. ACD says such manuals will be released shortly. I hope they will be of the same high quality as the software.

My only major reservation about the ACD products is their prices. For the complete ChemSketch 2.0/Tautomer/Dictionary/3D package, the list price is $445 ($195 for academic users and $95 for students). This package also comes bundled as part of the CNMR and HNMR packages, each of which lists at $3750 ($745 for academic users). Upgrades to future versions are available at 40% of the purchase cost. ACD also has academic site licenses for these packages at eight times the single-user cost. While I think that these prices may not be totally unreasonable for a large chemistry department, they are beyond the means of most moderate- to small-sized departments. ACD needs to find a pricing structure that will be within the budgets of such departments, as I believe that most chemists who try them would want to introduce them into their organic, analytical, and spectroscopic methods courses. Given the size of this market, a more reasonable price, if need be for special "student" versions of the software, would be bound to draw a large installed customer base.

I have been a confirmed Macintosh user most of my career and still use both Macintosh and Intel/Microsoft machines. However, the ACD software runs only on the latter platforms. I've installed it on platforms ranging from 486DX2-50 systems to Pentium Pro-200 systems using both the Windows for Workgroups 3.11 and the Windows 95 operating systems. All of the installations went very easily and I have found no significant bugs in the software. I have found installation to consume almost 100 MB of disk space for the complete software package and all of the multimedia demonstrations that I expect most people will want to leave on the computers for training purposes. The software ran well on the 486 system but I would recommend at least 8 MB of RAM, as I would for any graphics package to be used under Windows. Given the strong position that Apple retains in the educational and chemistry graphics market, ACD should consider releasing a Macintosh compatible version of their software.

Overall, I give these software packages a strong positive recommendation. They are easy to learn and very useful for both research and teaching. In my opinion, the freeware ChemSketch 1.0 is an unparalleled value and the commercial version 2.0 is a good value, comparable to its chemistry drawing competitors. Although other NMR prediction packages are available (1-10), those from ACD are the most user friendly that I have used. I strongly recommend that people download the demo versions or write to ACD for the CD. Then, their problem will be to try to find the money to purchase sufficient copies for use in both teaching and research.

References/Literature

1. Gurst, J. E. J. Chem. Educ. 1994, 71, 234.

2. Bell, H. M. J. Chem. Educ. 1993, 70, 996.

3. Bell, H. M. J. Chem. Educ. 1992, 69, 44.

4. Clark, M.; Thrasher, J. S. J. Chem. Educ. 1990, 67, 235.

5. Badger, R.; Lesniak, J.; Rutta, S. J. Chem. Educ. 1989, 66, 52.

6. Starkey, R. J. Chem. Educ. 1986, 63, 625.

7. Friedrich, E. C.; Runkle, K. G. J. Chem. Educ. 1986, 63, 127.

8. Ellison, A. J. Chem. Educ. 1983, 60, 425.

9. Honig, H. J. Chem. Educ. 1996, 73, 1078 (A review of a program from J. Chem. Educ.: Software, Vol. 4D, No. 2).

10. Blackman, A. J. J. Chem. Educ. 1996, 73, 1078 (A review of a program from J. Chem. Educ.: Software, Vol. 4D, No. 2).