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ChemSketch 3.5 and ACD/LogP dB 3.5 are products of Advanced Chemistry Development, Inc.
of Toronto, Canada. A full-featured chemical structure drawing program, Chem-Sketch 3.5
serves both as the entre into and the integrator among several other modular programs such
as ACD/LogP dB 3.5. Other ACD modules include programs for calculation of 13C-
and IH-NMR spectra, pKas, solubilities, boiling points, and vapor
pressures as well as software for generation of IUPAC names. As the name implies, ACD/logP
dB 3.5 is a program for calculation of octanol/water partition coefficients (log Poct)
of compounds. Such values indicate the lipophilicity or fat-seeking ability of molecules,
and they are of enormous importance to pharmaceutical and environ-mental chemists who
attempt to correlate molecular proper-ties with biological activity. The measurement of
these values, however, can be tedious, and an easy-to-use and accurate program for rapid
estimation of log Ps would be a useful tool.
ACD Labs/LogP dB 3.5 and ChemSketch 3.5 run only on IBM PC-compatible computers
operating under Windows 3.x or Windows 95/98. A Macintosh version of this software is not
currently available. Minimum system requirements include an 80486 processor (Pentium
recommended), VGA color monitor, 16 MB of RAM, at least 20 MB of free hard disk space, CD
ROM drive, and a mouse. The current version of the software is 32-bit compatible, but
actually 16 bit, which means that file names longer than eight characters are not
acceptable. Installation of the software ran off the CD-ROM drive and was straightforward
for the most part under Windows 95. I encountered some difficulty, however, in registering
ACD/ChemSketch and LogP dB, since there are several long, alphanumeric serial numbers
(provided by the vendor in separate documents called "Certificates of
Authenticity") associated with various parts of the software, and it was not clear
from the instructions which numbers should be entered.
ChemSketch 3.5. The number of features and tools included in ChemSketch 3.5 is
extensive and comparable to some of the most popular commercial structure drawing programs
such as ChemDraw, ChemWindow/Chemintosh, and ISIS Draw. Despite this complexity,
first-time users should have little trouble drawing attractive structures with relatively
little assistance. There is a full tutorial included in the documentation that is helpful
to novice users, but those already acquainted with any one of the drawing programs
mentioned above will probably not need to go through the entire tutorial.
The user interface of ChemSketch 3.5 differs significantly from ChemDraw and related
programs, yet I found structure input intuitive and user-friendly. There are two different
screens for drawing input: a "Structure" screen and another called
"Draw". Users draw molecules only in the Structure screen, which has menu and
button bars on the top of the drawing area. From the button bar users may choose an array
of bond types and also do structure editing by selecting from several options available.
Left-hand buttons consist of chemical element symbols that allow the user to select any
element in the periodic table as the default atom in a structure. On the right-hand side
of the drawing area are buttons to select substructures such as rings, chains of various
length, common group labels such as COOH, and labels for amino acids. Once the structure
is drawn, users may select the entire structure (by lasso, for example) and do operations
such as resize, rotation, and translation. Users may also calculate various physical
properties of the selected structure such as molecular weight, molecular formula, molar
refractivity, and molar volume, to name a few. Once the structure is selected, labels can
be adjusted for font type, size, and color. ChemSketch 3.5 also contains a 3D optimization
feature that will take a 2D structure and find a minimum-energy geometry, which is then
displayed on the screen in perspective, i.e., a flat structure for cyclohexane becomes a
chair conformation. Accompanying the drawing screen is a 3D molecular modeling module.
Users can import a selected structure into this module and render it as stick,
ball-and-stick, space-filling, wire mesh, and space filling, etc. 3D optimization in this
module, employing a molecular mechanics based algorithm, allows users to calculate bond
lengths and bond angles.
ChemSketch 3.5 comes equipped with a "Dictionary", which is a searchable
database of ca. 48 000 compounds. Users may select any compound from the database and
import it into the Structure screen on the fly. Several template files are available,
providing an array of carbohydrate, amino acid, arene, and ring structures as well as
orbital representations and reaction symbols. Users may produce their own template files
for future use or create templates on the fly when performing repetitive drawing
operations. Drawings may also be imported in several formats including Windows metafiles,
MDL MOL (.mol), ISIS SKETCH bin (.skc), and ChemDraw (.chm) and exported as Windows meta
and bitmap files, MDL MOL (.mol), ISIS SKETCH (.skc), ChemDraw (.chm), and GIF files.
The Draw screen of ChemSketch 3.5 appears at the press of a menu button, and it
contains the same information as the Structure screen. Once in the Draw screen mode, users
may edit their drawing by putting in text, reaction and pointer arrows, curves, and boxes.
Drawing Bezier curves is quite easy, and these may be edited to virtually any shape.
Editing the fill characteristics of shapes for texture and color is about as easy to do as
I have seen among the several commercial drawing programs familiar to me. Access to the 3D
modeling module is also possible via the Draw screen.
I noted a few characteristics of the ChemSketch 3.5 that I found to be a bit
cumbersome, such as having a separate Draw screen for editing instead of just one screen
for composing an entire drawing. Changing font size and type for chemical labels is not as
easy to do on the fly as it is with other commercial drawing software. Oddly in the
Structure screen, linear molecules, which contain all possible C - H bonds explicitly
shown after conversion to 3D structures, turn into Fischer projections when the 2D cleanup
option is applied; these structures do not appear anything like what was previously drawn.
In contrast to my overall favorable impression of ChemSketch 3.5 as a serious contender in
the competition among current, commercial structure drawing programs, however, these
quibbles are relatively minor. At the time of this writing, perhaps the best feature of
ChemSketch 3.5 is its availability free of charge by downloading from the website of ACD
Laboratories (www.acdlabs.com).
ACDLabs/LogP dB 3.5. Once a structure has been drawn in ChemSketch, it is possible
to calculate log P values of almost any organic compound simply by loading ACDLabs/ LogP
dB 3.5 from the ACD/Labs option on the top-of-screen menu bar of ChemSketch 3.5. A Calc
LogP button appears on the bottom of the screen, which, when pressed, places the user into
the calculation mode for determining log P. (Users may switch readily from the LogP mode
to the ChemSketch mode or back again at any time simply by pressing the ChemSk or Calc
LogP button, respectively, on the bottom of the screen.) A dialogue box appears prompting
the user to enter the melting point of the compound drawn if known (it is not necessary to
enter a melting point value for calculation of log P). Simply pressing the OK button
starts the calculation, and the result appears on a new screen. I found that all the
operations required for calculating log P values worked straightfor-wardly and smoothly.
ACDLabs/LogP db 3.5 uses what the vendor calls an "additive-constitutive"
algorithm somewhat similar to the approaches of Hansch and Rykker to calculate log P
values for almost any compound drawn in ChemSketch. The calculation engine adds up
contributions from separate atoms, structural fragments, and intramolecular interactions
between fragments, all derived from a database of over 5000 experimentally-obtained log P
values of over 3600 different compounds. Over 500 different functional group fragmental
contributions are used based upon the chemical structure and environment of the fragment.
Atom group contributions for
carbon atoms not involved in a functional group are based upon hybridization state,
number of hydrogens attached, and structural environment. Over 2000 types of
intermolecular contributions involving pairwise group interactions are also included in
the calculation. The program checks for tautomeric forms and advises users that log P
values of com-pounds having tautomeric forms may be difficult to obtain experimentally.
The program will calculate log P values of all tautomeric forms of a compound that are
generated automatically in ChemSketch, however.
There are limitation to the program, some of which include the following:
- ALLOWED ELEMENTS FOR DRAWN STRUCTURES lNCLUDE ONLY THE ATOMS C,
H, O, S, P, N. F, CL, BR, I, SE, SI, GE, PB, SN, AS, AND B.
- LOG P VALUES FOR CHARGED STRUCTURES, EXCEPT ZWITTERIONIC AMINO ACIDS AND PEPTIDES AND
STRUCTURES CONTAINING TETRAVALENT NITROGEN BONDED TO
OXYGEN, CANNOT BE OBTAINED.
- STRUCTURES MUST CONTAIN 255 ATOMS OR LESS.
- THE PROGRAM DOES NOT RECOGNIZE STEREOCHEMISTRY SUCH AS E VS Z C=C BONDS.
Each time the program calculates a log P value, it is stored along with the
corresponding structure in a "History" file (*.lp) that may be saved and later
retrieved. History files display up to 99 structures and log P values, and these may be
examined several at a time by pressing the History button at the bottom of the screen.
After opening a History file, structures may be added or deleted. History files may also
be saved as database files (*.sdf) for incorporation into the "DataBase" module
of the software (hence the designation "dB" in the program name). ACDLabs/LogP
dB 3.5 comes equipped with its own internal database of over 3600 compounds whose log P
values have been measured in the laboratory. Users may search this compendium according to
name, formula, log P value range, molecular weight, substructure, and literature
reference. As a search becomes more narrow, DataBase maintains two parallel search lists:
a broader list and one narrower, which is a subset of the broader list. A mouse click
allows users to switch between lists. Users may also import *.sdf files generated from the
History module to create their own searchable databases. I found using the internal
database easy, but encountered difficulty in searching the user database I created from an
imported *.sdf file. Lack of documentation on setting up and using user-designed databases
also exacerbated my troubles.
How good is ACDLabs/LogP dB 3.5 at predicting log P values of compounds outside the
data set it uses in the computation process? It is difficult to answer that question in
all cases, but it seemed appropriate that I should put the program to the test by
calculating log P values of some compounds I have worked with over the last several years.
These compounds are shown in Figure I (drawn using ChemSketch) and then also listed in
Table 1. They are all classified as plant phytoalexins (compounds produced by plants to
ward off microbial infection) or are known to have phytoalexin-like activity (i.e., the
abietic acid series). Log P values for many of these compounds have been measured,
sometimes by two different research groups.
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