acd/labs software for physical chemistryacd/chemsketch acd/pka accuracy extender display the...

A d v a n c e d C h e m i s t r y D e v e l o p m e n t A C D / L a b s 143

Tel: 1(416) 368-3435 • Fax: 1(416) 368-5596 • Toll Free: 1(800) 304-3988 • [email protected] • www.acdlabs.com

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PhysChem

Predict and Database Molecular Physical Properties

ACD/pKa DB

ACD/LogP DB

ACD/Solubility DB

ACD/LogD Suite

ACD/LogD Sol Suite

ACD/Sigma

ACD/Boiling Point

Choose Structural Modifications to Optimize Properties

ACD/Structure Design Suite

Perform Batch Calculations

ACD/PhysChem Batch

Enterprise-Wide Integration and Deployment

speach

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www.acdlabs.com/catalog/

A d v a n c e d C h e m i s t r y D e v e l o p m e n t A C D / L a b s144

Spectroscopy • Chromatography • PhysChem • Chemical Naming • Drawing and Databasing • Enterprise Solutions

Predict Before You Synthesize

Predict Before You Measure

Advanced Chemistry Development, Inc., (ACD/Labs) is committed to building software

that uses chemical structures to develop a deeper understanding of the analytical,

chemical, and biological behavior of organic compounds. Our suite of PhysChem

predictive tools allows researchers to evaluate a broad range of molecular properties

based on chemical structure even before the compound is synthesized. Knowledge of

molecular physical properties and individual contributions of particular molecular

fragments are invaluable in relating structural features with physicochemical

properties. A good understanding of these relationships helps the chemist to select

substituents that will furnish desired physicochemical properties in future compounds

for either pharmaceutical or environmental endpoints. ACD/Structure Design Suite

has specifically been designed for use in the optimization of novel lead compounds to

fine-tune and balance physical and molecular properties that impact drug-like ADME

parameters, and for agrochemical synthesis of targeted pesticides.

Our distinctive algorithms and extensive training sets of experimental values provide

top-quality accuracy of prediction for a wide range of chemical classes. Training of

the algorithms with the customer’s own experimental pKa, logP, and solubility values

further enhances the accuracy of prediction for novel chemical classes. Insight into

the calculation protocol allows chemists to better understand the structural

relationships that define the physicochemical properties of their compounds. Multiple

input and output formats, a variety of deployment options, and compatibility with

major third-party software packages and computer platforms make ACD/Labs

PhysChem products the preferred choice for chemical, biotech, and pharmaceutical

corporations.

The premier quality of our software is confirmed by numerous third-party reviews. A

number of major pharmaceutical companies have made ACD/Labs PhysChem tools

available to their scientists worldwide to assist them in making educated decisions in

drug design, preformulation, and physical property profiling. ACD/Labs PhysChem

products have been used to calculate properties for over 13 million organic structures

in the CAS Registry. This information is used daily by scientists worldwide when they

access compound information through STN®, SciFinder®, and SciFinder Scholar.

Who is it for?

• Medicinal chemists

• Preformulation specialists

• Computational chemists

• Cheminformatics specialists

• Agrochemical specialists

• High-throughput chemistry labs

• Compound acquisition groups of pharmaceutical companies

• Educators looking for an interactive way to teach chemistry to their students

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Table of ContentsMolecular Physical Property Prediction

Page

Calculate pKa values for your compound 146

Look up pKas in the database of experimental values 147

Use measurements to extend the accuracy of pKa prediction 147

Predict logP for the neutral form of your compound 149

Retrieve experimental logP values from the database 149

Calculate Polar Surface Area, Freely Rotatable Bonds, 149and Rule-of-5 properties

Train the logP prediction engine with your own data 150

Calculate the aqueous solubility of your compound as 152a function of pH

Search through the database of experimental solubility values 153

Use measurements to improve the accuracy of solubility prediction 153

Understand the pH profile of logD, and the 155pH dependent distribution of ionic species

Rapidly identify and evaluate structural modifications 158to aid in the optimization of the required properties

Evaluate a variety of Hammett sigma constants for 160selected fragments of your molecule or the substituents of your library

Predict the boiling point or vapor pressure of your compound 160

Calculate any or all of the chosen properties in Batch mode, 161suitable for working with tens of thousands of compounds at a time with minimal operator intervention

Calculate liquid molecular properties 162

Enable chemically intelligent structure handling and reporting 162

Provide access to computational tools for your whole organization 163

Automatically populate your MDL ISIS database with calculated values 163

Occasional users can access

ACD/Labs physicochemical

predictors and databases at

ACD/Labs Online

http://ilab.acdlabs.com

All product names throughout

this catalog are trademarks or

registered trademarks of their

respective holders.



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ACD/pKa DB

ACD/LogD Suite and ACD/LogD Sol Suite

ACD/LogP DB

ACD/Solubility DB

ACD/Sigma

ACD/Boiling Point

ACD/PhysChem Batch

ACD/PhysChem Accuracy Extender

ACD/pKa Accuracy Extender



ACD/MedChem Substituent Databases


Biologically active compounds should not be presumed to be neutral

species. Their ionization is described by pKa values.

ACD/pKa DB calculates accurate acid-base ionization constants

(pKa values) at 25°C and zero ionic strength in aqueous solutions for

almost any organic or inorganic structure. The accuracy of the

calculations is typically better than ±0.2 pKa units except for highly

complex structures or poorly characterized substituents, where the

accuracy is usually within ±0.5 pKa units.

Understand the behavior of your compounds in solution. Let the industry standard, ACD/pKa DB,predict accurate acid-base ionization constants for your compound.

ACD/pKa DB also includes:

ACD/ChemSketchACD/pKa Accuracy Extender

Display the chemical structure, pKa calculationsprotocol, references, and any additional datafor at-a-glance review.

Choose to calculate:

• Apparent pKa (exact or approximate) that

simulates experiment

• pKa microconstant for the drawn form,

with any combination of dissociated and

non-dissociated centers

• Single-value pKa for each dissociation

center when all other centers are

presumed neutral

Predict pKa Values

Draw, import, or edit chemical

structures. Produce quality

reports with ACD/ChemSketch

See Pg. 184

Exp. 12.01, 11.35, 7.83, 6.97, 2.90, 2.20 Calc. 12.08, 11.48, 8.24, 7.64, 2.97, 2.56

Exp. 3.72Calc. 3.82 ±0.10

Exp. 6.37Calc. 6.40 ± 0.30

Calculate properties for up to

999 structures at a time

See Pg. 156



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ACD/pKa DB


ACD/LogP DB

ACD/Solubility DB

ACD/Sigma

ACD/Boiling Point

ACD/PhysChem Batch







This expert tool allows users to define a new

ionization center and point of attachment for

a variable substituent, and assign a relevant

Hammett/Taft equation to define and

improve the accuracy of pKa prediction for

new chemical classes.

Use measurement data to increase the accuracy of pKa prediction.

The ACD/pKa DB Internal Database contains over

15,900 chemical structures with associated pKa

measurements. Experimental data was provided

in part by the internationally renowned BioByte

Corporation, making the ACD/pKa internal

database the largest commercially available

experimental pKa database.

Use Our Extensive Database of pKa Values, or Create Your Own

Since prediction is most valuable for novel compounds and classes, for which

no measured values may be available, it is essential to have a means of

expanding prediction accuracy to new chemical space. ACD/pKa DB offers

two tools that enable this type of customization:

• System Training with experimental pKa data

• ACD/pKa Accuracy Extender to design custom Hammett/Taft equations for

particular novel chemical classes. Resulting equations can be used for all

calculations made for this class by any ACD/Labs product that employs

pKa predictionSystem Training

Use Your Own Quality Measurements to Augment the Prediction

Create your own user databasesof pKa values. These databasesare not only handy for organizingyour in-house pKa data, but alsouseful for training the predictionalgorithm to enhance structuraldiversity and increase theaccuracy of prediction for yournovel/proprietary compoundclasses. Search by structure,fragment, or structural similarity,as well as values and references.

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R Substituent Experimental pKa Calculated pKa(before training)

Calculated pKa(after training)

a b b

-H –2.70 ± 0.1 –0.28 ± 0.50 –2.70 ± 0.01

-Cl –2.82 ± 0.1 –0.04 ± 0.50 –3.08 ± 0.1

-NO2 –3.5 ± 0.1 –0.83 ± 0.50 –3.87 ± 0.1

Average Deviation 2.62 0.21

a) Tables of rate and equilibrium constants of heterolytic organic reactions, Ed. V. A. Palm, Moscow, 1975b) Calculated using ACD/pKa DB version10.0

ACD/pKa DB continued...



A detailed look at ACD/pKa DB features

Prediction Calculate several different pKa values:

• Apparent pKa (exact or approximate)

• pKa microconstant for the drawn form

• Single-value pKa for each dissociation center when all othercenters are presumed neutral

Improve the accuracy of prediction for novel classes by training thealgorithm with your own data

Check and choose tautomeric forms

Compute your values at the highest speed while maintaining anoutstanding quality of calculation

DisplayView the chemical structure, explanation of pKa calculations,references, and any applicable warnings

Relate the calculated pKa values to the corresponding ionizationcenters

Review the predominant ionization forms and calculation protocol

Display up to 999 structures with the calculated pKa values in theHistory window

Highlight the fragments of the molecule that were requested in theoriginal query, and choose the color of display

Content/Library Search the internal database which contains over 15,900 structureswith experimental pKa data and references to the original researchand review papers. The database is searchable by structure, structuresimilarity, substructure, IUPAC name, pKa value, and other fields

Search the database for tautomeric forms

View database entries individually, in Tile view, or as a table

Choose structures or values for further review by selecting the recordsin Table or Tile view

Reporting Customize and print your results. Add references and calculationprotocols to the printout

Send a History file or Database record by e-mail from within thesoftware

Print reports directly from a custom designed screen form

DatabasingBuild your own User Databases of pKa values

Set a warning for inconsistent data entry

Compare, merge, or find common intersecting records in thedatabases

Use Boolean logic and comparison operators to perform advancedsearches

Create graphs in the database window for better data visualization

Add formulas into database fields to create customized queries

Take advantage of our database format (PhysChem Database—*.pcd), where each record can also include logP, logD, solubility, andpKa experimental values, depending on the selection of availablemodules

Input/Output Use the intuitive ACD/ChemSketch interface to draw or importchemical structures

Import and process SDfiles with up to 999 structures using thedesktop package. For an SDfile of chemical structures without pKavalues, the program will automatically calculate pKa data on import

Map data to the chosen fields during import from an SDfile

Export results in SDfile format, and customize fields while maintainingoriginal attributes

Advanced ToolsTrain the prediction engine with User Databases of pKa values toenhance the structural diversity and increase the accuracy ofprediction for your novel/proprietary compound classes

Take advantage of augmented training options that help users easilyselect compounds for training via a series of checklists and menucommands

Train the algorithms with multiple databases simultaneously toreduce training times

Use the advanced training tool—ACD/pKa Accuracy Extender

Utilise add-ons to resolve specific challenges, e.g., remove thecounter-ions from salts drawn with a covalent bond or in ionic form

Take advantage of easy-to-use scripting tools to calculate additionalparameters

IntegrationACD/Labs' PhysChem desktop prediction modules are closelyintegrated to provide a simple workflow

Add results from your own computational tools to the ACD/LabsPhysChem databases

Take advantage of the additional flexibility afforded via MDL ISISintegration

Calculate thousands of pKa values at once (ACD/PhysChem Batch)

Enable pKa calculation in the Calculate Properties options of otherACD/Labs products

ACD/pKa DB is part of ACD/LogD Suite and ACD/LogD Sol Suite

For more information, please visit our Web site atwww.acdlabs.com/pka/

For a complete listing of available structure drawing and reportingfeatures, refer to the ACD/ChemSketch description (pg. 184)



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ACD/LogP DB

ACD/Solubility DB

ACD/Sigma

ACD/Boiling Point

ACD/PhysChem Batch







For neutral compounds, logP serves as a quantitative descriptor of

lipophilicity. With ACD/LogP DB, you can obtain the octanol-water

partition coefficient (logP), and calculate molecular Polar Surface Area

(PSA), Freely Rotatable Bonds (FRB), and Lipinski’s “Rule-of-5”

parameters. Accuracy of logP calculation in most cases is ±0.3 logP

units or better. In addition, ACD/LogP DB predicts the

bioconcentration factor and the organic carbon adsorption

coefficient for the neutral form of your compound.

LogP defines lipophilicity, the major determinant of pharmacokinetic properties.

ACD/LogP DB also includes:

ACD/ChemSketchACD/PhysChem Accuracy Extender (LogP module)

ACD/LogP DB uses the structure-fragment approach toaccurately predict the partition coefficient. New fragmentalincrements are added with each new release.

Review the calculationprotocol used to calculatethe logP value. Predict themolecular Polar SurfaceArea (PSA), Freely RotatableBonds (FRB), and Lipinski’s“Rule-of-5” parameters.

Predict LogP and Related Properties

The internal database of experimental logP

values contains over 18,400 compounds.

View the internal logP database oryour own logP database inmultiple record tile or table view.

Reference Thousands of Experimental Values, and Store Your Own

Electrolyte Groups That Dissociate During Partitioning

Display Warning in ACD/LogP DB

Display pH Dependence in ACD/LogD Suite

Search in User Database

Search in LogP Site of Potential Tautomeric

Rearrangement

Inter-fragmental Interactions

Unique Fragment, not Found in the Internal Fragment

Databases

Display Warning

Use Secondary Algorithms

Trained Increments




See Pg. 184



See Pg. 156

Obtain single logP value

calculations in

ACD/ChemSketch

See Pg. 184



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ACD/LogP DB

ACD/Solubility DB

ACD/Sigma

ACD/Boiling Point

ACD/PhysChem Batch







Developed for advanced users, ACD/PhysChem Accuracy Extender

(LogP module) provides a sophisticated means of improving

prediction accuracy using your in-house measurements. This

advanced training capability makes ACD/Labs' LogP and LogD

products unsurpassed in both quality and versatility. ACD/PhysChem

Accuracy Extender helps users take full advantage of their own work

by extracting fragments and interaction increments from their

structures and training the ACD/LogP software with the available

experimental data.

Achieve high-throughput and high accuracy by enhancing prediction with targeted measurements.

1) Import structures from an SDfile that contains experimentallogP or logD values. Corresponding databases of fragmentsand chains are created automatically. You can edit thedatabases, adding new fragments when you see fit, andmanually define your own user fragments.

Compare ACD/LogP SystemTraining and ACD/PhysChem

Accuracy Extender

System Training ACD/PhysChem Accuracy Extender

Easy to use Powerful expert tool

Improves accuracy for related compounds Extends accuracy to diverse chemical space

No analysis required by user Offers results analysis, statistics, and diagnostic ability

Ideal for small training data sets Generally requires large training data sets

4) Edit the increment values for new fragments and chainscalculated by the program, delete unwanted moleculesfrom the calculation, and recalculate the regression.

5) Combine the resulting files with the standard ACD/LogPDB fragment databases to dramatically improve thequality of calculation for logP, logD, and pH-dependentsolubility.

3) Review thecalculations toexamine the list ofstructures used indetermining a specificincrement, or graph allor a subset of the datato view moleculescontaining a specificchain or fragment.

2) Based on your selected list,ACD/PhysChem Accuracy Extendercalculates increments for new fragments,and chains from your molecules.

Use Your Own Measurements and Proprietary Chemistry to ImproveACD/LogP DB Prediction with ACD/LogP System Training and ACD/PhysChemAccuracy Extender (LogP module)

ACD/LogP DB continued...

In our test, it took 20

minutes to perform the

regression for a dataset

with 7710 structures,

from which 3946 new

fragment increments

were obtained



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A detailed look at ACD/LogP DB features

PredictionCalculate the following properties for the neutral form of a molecule:• LogP and the Calculation Protocol• Polar Surface Area (PSA)• Freely Rotatable Bonds (FRB)• Number of H-Donors and Acceptors• Bioconcentration Factor and the Organic Carbon Absorption

Coefficient for the neutral species

Check the “Rule of 5” properties



DisplayView the chemical structure of your compound with clearly markedinternally-defined fragments used for the calculation

Display up to 999 structures with the calculated logP values

Highlight the fragments of the molecule that were requested in theoriginal query. Choose the color of display and atom color

Content/LibraryTake advantage of an internal database of experimental logP valueswhich contains over 18,400 compounds with references to theoriginal scientific articles or reviews

Search the database by structure, substructure, IUPAC name, logPvalue, and other fields. Also, search for tautomeric forms

View database entries individually, in Tile view , or as a table


DatabasingCreate graphs in the database window for better data visualization

Add formulas to database fields to create customized queries

Take advantage of our database format (PhysChem Database—*.pcd), where each record can also include logP, logD, solubility, andpKa experimental values, depending on the selection of availablemodules

Build your own User Database of logP values to organize andsearch your in-house logP data




ReportingCustomize, print, or copy your report to the clipboard. Add referencesand the calculation protocol

Send a History file or Database record by e-mail


Import/ExportImport and process SDfiles with up to 999 structures using thedesktop ACD/LogP DB package. For an SDfile of chemical structures,the program will automatically calculate logP data on import


Advanced ToolsUse your own User Databases for algorithm training to extendstructural diversity and increase the accuracy of prediction for yournovel/proprietary compound classes

Take advantage of the training options that help users easily selectcompounds for training via checklists and menu commands

Train with multiple databases simultaneously to reduce training timeand improve the accuracy of calculations for user datasets


Transfer logP user data to a logP user fragments file

View the histogram of structures and user-defined experimental dataused in System Training

Use the advanced training tool for LogP/LogD products—ACD/PhysChem Accuracy Extender (LogP module), featuring:

• Step-by-step wizard option

• Convenient and user-friendly results window

Complete regression analysis for thousands of compounds in minutes

Use the convenient add-ons to resolve specific challenges, e.g.,remove the counterions from salts drawn with a covalent bond or inionic form



Benefit from enhanced integration with ACD/ChromManager: transfer experimental chromatographic data (containing logP)into the logP training database


Calculate thousands of logP values at once (ACD/PhysChem Batch)

Enable logP, BCF, and Koc calculations in the Calculate Propertiesoptions of other ACD/Labs products

ACD/LogP DB is part of ACD/LogD Suite and ACD/LogD Sol Suite

For more information, please visit our Web site atwww.acdlabs.com/logp/




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ACD/LogP DB

ACD/Solubility DB

ACD/Sigma

ACD/Boiling Point

ACD/PhysChem Batch







Get early insight into your molecule’s properties through the

prediction of aqueous solubility at any pH. Find out if your newly

synthesized solvent-soluble compound has the potential to become

an orally-administered drug. ACD/Solubility DB determines the

aqueous solubility of organic compounds for pH values from 0.0 to

14.0, at 25°C. The accuracy of calculations for simple structures is

usually better than 0.2-0.5 logS units; for complex structures, it is

better than 0.5-1.0 logS units.

Accurate prediction of solubility as a function of pH.

ACD/Solubility DB also includes:

ACD/ChemSketchACD/PhysChem Accuracy Extender

Review predicted apparent solubility vs. pHprofile, intrinsic solubility, and solubility inunbuffered water for your structure, as well asreferences to experimental research, in theResults window.

Display the relativeconcentrations of allionic forms of yourcompound as afunction of pH.

In a study of 2094 compounds of pharmaceuticalinterest, 88.5% of the predictions had a maximumabsolute error of prediction below 1 log unit, ascompared to 84% in version 8.0.

Calculate Aqueous Solubility

Export your predicted Solubilityprofile to ACD/Curve Managerto process and store it togetherwith the experimentally derivedsolubility graphs

ACD/Curve Manager (Pg. 108)

40%

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0.5 1 1.5 2 2.5 3

Maximum Absolute Error

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See Pg. 184



See Pg. 156



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ACD/pKa DB


ACD/LogP DB

ACD/Solubility DB

ACD/Sigma

ACD/Boiling Point

ACD/PhysChem Batch







This advanced tool provides expert users with the ability

to add new increments (fragments) to the existing

prediction model, in order to increase the accuracy of

solubility predictions for specific classes of organic

compounds. Structures and corresponding experimental

values (imported from ACD/ChemSketch or as SDfiles) are

incorporated in regression calculations to evaluate new

structural fragments and their associated solubility

increments. The additional increments are then

combined with ACD/Labs’ internal pool of experimental

values to augment solubility predictions.

Augment predictions with experimental data for new structural fragments.

Two types of training are available forACD/Labs' solubility algorithm:

1. System Training with experimentalsolubility values from a user’s database

2. Expert algorithm enhancement withACD/PhysChem Accuracy Extender(Solubility module)

When carrying out algorithm training,users can choose the type of solubilitydata they are interested in: intrinsicsolubility or solubility at a specific pH. Inthe latter case, intrinsic solubility will becalculated and marked accordingly.

Create your own databases of solubility

values using ACD/Solubility DB. Look up a

compound in the internal database of

over 6000 compounds with experimental

solubility values. This internal database is

fully searchable and contains chemical

structures, names, synonyms, IUPAC

names, experimental data, and references

to the original articles.

Solubility trainingwindow

Experimentalsolubility values are accepted in 61different units ofmeasurement, from“grams per liter” to“mole fraction”.

ACD/PhysChem AccuracyExtender offers a Wizardto help users build newincrement datasets andevaluate the results.

Look up Experimental Values, from Your Own Lab orfrom Publicly Available Sources

Train the solubility calculation algorithm

with experimental solubility values to

improve prediction accuracy for novel or

unique chemical classes.

Use Experimental Solubility Data to Augment the Prediction

ACD/Solubility DB continued...



A detailed look at ACD/Solubility DB features

PredictionCalculate several types of solubility:

• Intrinsic solubility or solubility of a neutral form of the compound

• Solubility as a function of pH

• Solubility observed when a pure compound is added to pure (unbuffered) water



DisplayView the chemical structure and results of the solubility calculation asa function of pH in graphic and tabular forms

View the content of each ionic form of your compound in thesolution as a function of pH

Obtain values for intrinsic solubility and solubility of the purecompound in water with the corresponding pH

Display up to 999 structures with the calculated values in theHistory window

Highlight the fragments of the molecule that were requested in theoriginal query. Choose the color of display and atom color

Content/LibrarySearch the internal database which contains experimental solubilitydata with experimental conditions, if available. The database issearchable by structure, structure similarity, substructure, IUPAC name,solubility value, and other fields

Internal database contains over 6000 chemical structures withreferences to the original research and review papers


DatabasingCreate your own Solubility Databases to store experimentalsolubility values




Create graphs in the database window for better data visualization

Add formulas into database fields to create customized queries

Take advantage of our database format (PhysChem Database—*.pcd), where each record can also include logP, logD, solubility, andpKa experimental values, depending on the available modules

ReportingCustomize and print your results. Add references and calculationreports to the print out



Import/ExportUse the intuitive ACD/ChemSketch interface to draw or importchemical structures

Import and process SDfiles with up to 999 structures using thedesktop ACD/Solubility DB package. The program will automaticallycalculate the intrinsic solubility on import

Map data to the chosen fields during import from an SDfile


Advanced ToolsUse your own User Databases for algorithm training to extendstructural diversity and increase the accuracy of prediction for yournovel/proprietary compounds. Train with multiple databasessimultaneously to reduce training time and improve the accuracy ofcalculations for user datasets

Use the advanced training tool—ACD/PhysChem AccuracyExtender (Solubility module)–featuring the step-by-step wizardoption to build new fragmental increments and augment predictionaccuracy


Use convenient add-ons to resolve specific challenges, e.g., removethe counterions from salts drawn with a covalent bond or in ionicform




Calculate thousands of solubility values at once (ACD/PhysChemBatch)

Enable solubility calculations in the Calculate Properties options ofother ACD/Labs products

Export the solubility pH profile to ACD/Curve Manager

ACD/Solubility DB is part of ACD/LogD Sol Suite

For more information, please visit our Web site atwww.acdlabs.com/solubility/




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ACD/pKa DB


ACD/LogP DB

ACD/Solubility DB

ACD/Sigma

ACD/Boiling Point

ACD/PhysChem Batch







ACD/LogD Suite includes, in addition to the unique tool for calculation

of logD (ACD/LogD), the fully-featured ACD/pKa DB and ACD/LogP DB

programs for calculating individual ionization constants and partition

coefficients of neutral species, and ACD/Sigma, which allows you to

obtain electronic substituent constants.

In addition, this package also predicts polar surface area, number of

freely rotatable bonds, and pH profiles of bioconcentration factor

(BCF), adsorption coefficient (Koc), and “Rule-of-5” properties.

ACD/LogD Sol Suite also delivers fully-featured ACD/Solubility DB for

the calculation of aqueous solubility of electrolytes and non-

electrolytes at any pH, in addition to the above mentioned array of

tools.

A comprehensive toolset for evaluating the PhysChem properties of prospective compounds.

ACD/LogD Suite includes:

ACD/LogDACD/pKa DB with ACD/pKa Accuracy ExtenderACD/LogP DB ACD/PhysChem Accuracy Extender (LogP module)ACD/SigmaACD/ChemSketch

ACD/LogD Sol Suite includes:

ACD/Solubility DBACD/LogDACD/pKa DB with ACD/pKa Accuracy ExtenderACD/LogP DBACD/PhysChem Accuracy ExtenderACD/SigmaACD/ChemSketch

Review components of thelogD calculation and the pHdependant logD profile.Display logD, Koc, and BCF pHprofiles, calculated with orwithout ion-pair partitioning,to gain insight into thebehavior of your compound.

Review the relative concentrationsof all ionic forms of yourcompound as a function of pH.

Partially Dissociated Species DO EXISTin Octanol-Water Solutions!

The key component of ACD/LogD Suite is its

LogD module. LogP, the partition coefficient

for neutral species, is not an appropriate

descriptor for partially dissociated

compounds. Instead, logD, the distribution

coefficient, is the key parameter.

ACD/LogD, pH-Dependent Octanol-Water Distribution Coefficient




See Pg. 184



For small libraries and data sets with fewer than

999 structures, you can import and process

SDfiles using the standalone desktop software.

Calculated properties can be exported back to

the SDfile with all of the original data intact, or

saved as a report from a customized

ACD/ChemSketch reporting template. All

calculation protocols can be reviewed one-by-

one through the standard ACD/Labs desktop

interface.

For customers who haveseveral ACD/PhysChemmodules, the integratedinterface allows the fullphysicochemical profile ofeach compound to becalculated at the press of abutton, viewed in a singlescreen (History Window),easily compiled into a report,and exported to an SDfile.

Assisted Multi-Generation (AMG) Capability

Each of the separate PhysChem modules

contains its own database of experimental

values with structures and references to the

original research. When a number of modules

are installed together (such as in ACD/LogD

Suite), users gain access to a single unified

database that accumulates a wealth of

experimental knowledge. Futhermore, users can

create their own databases of experimental

results that can be used to train ACD/Labs

prediction algorithms with unique values

characteristic of their distinctive chemistry.

Stored data can be retrieved through a variety of

search options, including search by structure,

substructure, structural similarity, stereoisomers,

text, physicochemical property values, and user-

defined values. Custom rules of data

interpretation can be set by adding formulas to

the data fields (boolean and comparison

operators are also accepted). The quality of

stored information can be controlled via data

entry forms.

Customers can add results from their own

computational tools to ACD/Labs’ PhysChem

databases through file exchange in the broadly

accepted MDL SDfile format.

Unified Database of Physicochemical Properties

Multiple properties of multiple compounds on your desktop.

View all experimental properties for thecompound at-a-glance, and select those tobe used in algorithm training.

View data as a table, sort,select the desired records,and export the values toMicrosoft Excel.

Create graphs to visualize data inyour database and evaluate trends.



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For information on modules other than ACD/LogD, please refer to the specific product descriptions

A detailed look at ACD/LogD Suite and ACD/LogD Sol Suite features

PredictionCalculate logD at any pH with or without ion-pair partitioning

Determine the percentage of the dominant form in aqueous andorganic phases

Calculate the bioconcentration factor (BCF) and adsorption coefficient (Koc) at any pH


DisplayView the chemical structure of your compound and a choice ofcalculated logD, BCF, or Koc as a function of pH. Compare the logDprofile with the logP value for the neutral form of the compound

Display the relative concentrations of all ionic forms of yourcompound as a function of pH

Display up to 999 structures with calculated values in the Historywindow for convenient data interpretation. All of the properties canbe viewed in one window

ReportingCustomize, print, or copy your report to the clipboard. Add referencesand the calculation protocol



Import/ExportUse the intuitive ACD/ChemSketch interface to draw or importchemical structures

Import and process SDfiles with up to 999 structures using thedesktop software

Export results into SDfile format; customize fields

DatabasingCreate your own database of logP or logD values, accessible via theDatabase window

Advanced ToolsUse experimental pKa, logP/logD, and solubility values from customUser Databases to improve the accuracy of logD predictions for yournovel/proprietary compounds

Mark values and compounds in the User Database of experimentalvalues to include them in System Training and improve logDcalculation accuracy

Train with multiple databases simultaneously to reduce training timeand improve the accuracy of calculations for user datasets

Use expert algorithm training tools for logP/logD, solubility, and pKaproducts—ACD/PhysChem Accuracy Extender (LogP andSolubility modules) and ACD/pKa Accuracy Extender



Take advantage of our database format (PhysChem Database—*.pcd), where each record can also include logP, logD, solubility, andpKa experimental values, depending on the available modules



Calculate thousands of logD and related values at once(ACD/PhysChem Batch)

Export the logD pH profile to ACD/Curve Manager

For more information, please visit our Web site atwww.acdlabs.com/logdsuite/




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ACD/pKa DB


ACD/LogP DB

ACD/Solubility DB

ACD/Sigma

ACD/Boiling Point

ACD/PhysChem Batch






ACD/PhysChem Accuracy ExtenderACD/Structure Design Suite was developed to complement the

in-depth chemical knowledge of synthetic chemists, and to assist

them in rapidly identifying structural modifications in the design of

compounds with improved molecular physical properties that impact

ADME characteristics or environmental endpoints.

This intuitive design suite of computational tools uses property trends

and an extensive database of substituents to systematically suggest

modifications that are expected to yield the desired characteristics.

Structure Design Suite utilizes our renowned logP, pKa, logD, and

solubility prediction tools, which are used daily at nearly every major

pharmaceutical research company worldwide.

Progress from an unoptimized parent compound to a selection of analogs with the desiredphysicochemical properties.

ACD/Structure Design Suite includes:

ACD/Structure Designer moduleACD/Solubility DB ACD/LogDACD/pKa DB with ACD/pKa Accuracy ExtenderACD/LogP DBACD/PhysChem Accuracy ExtenderACD/Sigma ACD/Substituent DatabaseACD/ChemSketch

The software helps optimize the selected

fragment within a molecule to achieve the

desired molecular physical properties.

Substituent modifications expected to result in

improved properties are automatically

selected from the database using pre-defined

rules that link physicochemical properties to

structural elements of the compound (such as

a Hammett equation, or a model that

describes the impact of pKa on solubility). The

list of suggested substituent modifications can

be further refined via text and structure

searches, or cherry-picked manually. Analogs

are then automatically created via an

enumeration tool and their associated

physicochemical properties are calculated.

The structures and properties can be reviewed

and evaluated using powerful graphing tools

and a customizable interface. If necessary,

result data can be exported into Microsoft

Excel for further structure activity relationship

(SAR) studies.

NN

N

CH3

CH3

Cl

Modify

Parent Compound

Optimize

Refine Results

Evaluate

SynthesizeOutput from ACD/Structure Design Suite:

· Selection of analogs with optimizedphysical properties and fully calculatedphysicochemical property data

· Choice of representations for results (graphical, Tile view, Table view, or individual view of fullPhysChem profile for each analog) to provide facile evaluation



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Expert users can incorporate their own

models and algorithms that link chemical

structures, topological descriptors,

physicochemical properties, or other

parameters to desired endpoints for

evaluation of favorable structural

modifications to unoptimized candidates.

They can also build their own substituent

database to reflect fragments characteristic

of their proprietary chemistry.

Since the software includes a number of

ACD/Labs predictive physicochemical

modules, suggested modifications can be

further evaluated by conducting an in-depth

review of the prediction protocols. For

example, users can examine pKa values of

the parent molecule to assess the impact of

particular functional groups as revealed in

their corresponding Hammett-Taft equations;

or evaluate logD and solubility pH profiles of

suggested analogs to ensure that proposed

structural modifications result in desired

molecular properties at the pH range of

interest.

The suite comes with a database containing

over 29,000 substituent fragments. This

database includes structural information,

pKa values, molar volume, molar refractivity,

Hansch (π) constants, and a variety of

Hammett Sigma (σ) electronic substituent

constants. Retrieved data can be viewed as a

table, in Tile view, or one-by-one, and

reported in a variety of formats.

The substituent database can besearched by chemical structure,substructure, or structural similarity;and all of the included parameters,using formulas, Boolean logic, andcomparison operators.

Draw, import, or drag-and-drop

structures from existing ChemDraw files,

ISIS/Draw files, SDfiles, rxnfiles, or

molfiles directly into ACD/ChemSketch,

and create customized reports.

ACD/ChemSketch

See Pg. 184

ACD/Structure Design Suite continued...

Export your results into Microsoft Excelto help build SAR tables.

Review the full-array of molecular physical propertiesat-a-glance for each analog.

The optimization Wizard guidesusers through the process.

For more information, please visit our Web site atwww.acdlabs.com/sds/



A detailed look at ACD/Sigmafeatures

PredictionCalculate:

• Hammett-type electronic substituent constants• Molar volume• Molar refractivity

DisplayView the chemical structure and results of the calculations in theintuitive ACD/ChemSketch interface

ReportingCustomize and print your results using all of the tools available viaACD/ChemSketch

IntegrationCalculate thousands of σ values at once for selected fragments ofyour molecule or the substituents of your library (also available aspart of ACD/PhysChem Batch, ACD/LogD Batch, and ACD/LogD SolBatch). Either one SDfile, containing a list of substituents, or twoSDfiles, describing the core molecule (scaffold) and the library, can beused to generate sigma values

ACD/Sigma is also part of ACD/LogD Suite and ACD/LogD Sol Suite

For more information, please visit our Web site atwww.acdlabs.com/sigma/

Calculate the sigma value for any desired substituent attached to achemical core by a single bond.

Besides several σ values, ACD/Sigma calculates steric constants(molar volume and molar refractivity) for fragments of your choice.

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ACD/pKa DB


ACD/LogP DB

ACD/Solubility DB

ACD/Sigma

ACD/Boiling Point

ACD/PhysChem Batch







• Rationalize experimental trends

• Correlate structural features with new properties

• Plan SAR experiments

• Design libraries

Critical physical organic parameters,available instantly.

A detailed look at ACD/Boiling Point features

PredictionCalculate:

• Boiling point at the atmospheric pressure• Vapor pressure over a wide range of temperatures• Enthalpy of vaporization at the boiling point• Flash point

DisplayView the chemical structure, boiling point vs. pressure, or vaporpressure vs. temperature in tabular form and as a graph

ReportingCustomize and print your results using all of the tools available via theACD/ChemSketch interface

Additional ToolsObtain the enthalpy of vaporization at the boiling point and flashpoint

Add experimental boiling point data

IntegrationTake advantage of the additional flexibility afforded via MDL ISISintegration

Calculate thousands of boiling point and vapor pressure valuesat once (ACD/PhysChem Batch)

Enable boiling point calculations in the Calculate Properties options ofother ACD/Labs products

For more information, please visit our Web site atwww.acdlabs.com/bp/

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ACD/pKa DB


ACD/LogP DB

ACD/Solubility DB

ACD/Sigma

ACD/Boiling Point

ACD/PhysChem Batch







Estimate the persistence of a compound and its products of photolysis

based on accurate prediction of Pvap as a function of temperature.

Calculate the boiling point, the enthalpy of vaporization at the boiling

point, and the flash point.

The environmental fate of many compoundsdepends strongly on vapor pressure.

Calculate boiling point as afunction of pressure from 0.001to 7600 torr.

Identify and summarize, ina histogram, the fragment

components that influenceflash point prediction.



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ACD/LogP DB

ACD/Solubility DB

ACD/Sigma

ACD/Boiling Point

ACD/PhysChem Batch







Whether filtering virtual libraries or populating the corporate database, use

ACD/PhysChem Batch to automatically calculate properties for hundreds of

thousands of compounds in unattended mode.

Quality, quantity, and speed in PhysChem property prediction.

Input data from MDL ISIS/Base and SDfiles, SMILES

text files, or ACD/ChemFolder databases. Calculated

data can be saved to MDL ISIS/Base, SDfiles,

ACD/ChemFolder, or text files.

Choose to output the calculated values in three

different ways:

• Directly to the native database, with other data

fields preserved

• As a database in another supported format

• As a summary table with results and structure ID

Batch output is fully

compatible with

MDL ISIS/Base,

SDfiles, and Microsoft

Office applications.

Add values from User Databases

to batch calculations to enhance

the prediction algorithm, and

hence prediction accuracy, for

your unique chemical classes.

For more information, please visit our Web site at www.acdlabs.com/physchembatch/

ACD/PhysChem Batch is available in avariety of property-specific modules.

Each module also includes:

The respective desktop software module andACD/ChemSketch

Calculation options depend on the variety ofmodules selected.

Batch versions are available to run onWindows and Linux-based systems for anyof the following products:

ACD/LogP DBACD/pKa DBACD/LogD Suite ACD/Boiling Point ACD/Solubility DBACD/SigmaACD/ChemSketch (providing fast calculation of density, molar volume,molar refractivity, index of refraction,parachor, and the dielectric constant)

Import and export thefollowing formats:

• ACD/ChemFolder database• SMILES text file• MDL ISIS/Base (.DB, .RDF)• SDfile



Draw, Import, and Modify Your Structures, and Create Reportswith ACD/ChemSketch

ACD/ChemSketch is a universal chemical drawing and graphics package that helps you:

• Draw molecules, reactions, and schematic diagrams

• Calculate molecular properties

• Design professional reports and presentations

Chemical Intelligence: Structure

In addition to its unsurpassed chemical drawing capabilities,

ACD/ChemSketch enables import of ChemDraw files, MDL ISIS/Draw

files, SDfiles, rxnfiles, molfiles, and extended (V3000) molfiles.

ACD/Dictionary offers the ability to easily obtain a structure from its

trivial or systematic name.

Poorly drawn structures can lead to misinterpretation. Optimization

algorithms correct structure drawings and highlight errors or

ambiguities.

Property Calculation

A number of molecular properties, and several types of chemical nomenclature can

be generated within ACD/ChemSketch:

ACD/ChemSketch Reports

Since ChemSketch offers drawing tools, it is

ideal for creating and formatting reports.

Integration with all ACD/Labs products

ensures that you can produce your final

report at the click of a button. Reports can be

saved as Adobe PDF files, or cut and pasted

into Microsoft Office applications.

Data Handling

Your Adobe Acrobat or Microsoft Word

reports, standard SDfiles, and various

ACD/Labs databases can be searched by

chemical structure or substructure within

your computer or network directories using

ACD/ChemSketch.

ACD/3D Viewer

Tautomerism can easily introduce a source of miscommunication that

leads to errors. ACD/ChemSketch will provide a warning if different

tautomeric forms are possible, and give you the option to select and

continue with the tautomer of interest to you.

Molar Refractivity (cm3)

Molar Volume (cm3)Parachor (cm3)

Surface Tension (dyne/cm)

C9H8O4

Density (g/cm3)

Dielectric Constant

Polarizability (cm3)

Monoisotopic Mass (Da)

Nominal Mass (Da)

Average Mass (Da)

IUPAC Naming (restricted version)

O

O

O

OH

CH3

Aspirin 2-(acetyloxy)benzoic acidTrivial Name

C(60.00%) H(4.48%) O(35.52%)

InChI SMILES

You can also print

your report directly

from a custom

designed screen form

ACD/ChemSketch

See Pg. 184



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Easy deployment of chemical prediction and database searching, as

well as integration with both third-party and customer in-house

software, is of paramount importance for the modern laboratory.Several ACD/Labs products enable server- or browser-based access to

predictions and databases, among them:

• Tools to seamlessly integrate ACD/Labs software with MDL ISIS and

CambridgeSoft ChemDraw products—ACD/Labs Add-ins for ISIS and

ACD/Labs Extension for ChemDraw

• Web-based access to chemical information, naming, and property

prediction for your compounds throughout the enterprise—

ACD/I-Lab: Intranet Edition

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ACD/Labs Add-ins for ISIS


ACD/I-Lab: Web-based Predictions

ACD/Labs ActiveX Components

ACD/Web Librarian

ACD/Mol2Gif

ISIS Integration



ACD/MolX

ACD/SpecX

ACD/SpecManager Enterprise

ACD/ChromManager Enterprise

ACD/Mol2Gif

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ACD/Labs Predictors for Intranets

ACD/Workflow Manager

ACD/Automation Server

ACD/NuGenesis Integration

ACD/Web Librarian Web Services

ACD/Structure Drawing Applet

ACD/ChemCoder SDK


ACD/ChemFolder Enterprise

Access the power and accuracy of any ACD/Labs predictive algorithm

from the ISIS interface. Search any ACD/Labs database from within

ISIS. Automatically populate your ISIS database with calculated values

of logP, pKa, logD, solubility, boiling point, vapor pressure, and so on,

with uncertainty limits and warning messages (if desired).

Also includes: ACD/Labs Add-in for ISIS/Draw

Use all of the predictive

power of ACD/Labs in your

ISIS environment. Export

experimental data for

ACD/Labs batch predictions.

Improve prediction accuracy by

training with your own

databases.

Enterprise-Wide Integration and Deployment

Enterprise Solutions and

Software Integration

See Pg. 218


(enabled by ACD/I-Lab: Intranet Edition)

are available as:

ACD/LogP DB for Intranets

ACD/pKa DB for Intranets

ACD/Boiling Point for Intranets

ACD/LogD Suite for Intranets

ACD/LogD Sol Suite for Intranets

ACD/Solubility DB for IntranetsCalculate accurate acid-base ionization

constants (pKa values).

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ACD/I-Lab: Web-based Predictions

ACD/Labs ActiveX Components

ACD/Web Librarian

ACD/Mol2Gif

ISIS Integration



ACD/MolX

ACD/SpecX


ACD/ChromManager Enterprise

ACD/Mol2Gif

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ACD/Workflow Manager

ACD/Automation Server

ACD/NuGenesis Integration

ACD/Web Librarian Web Services

ACD/Structure Drawing Applet

ACD/ChemCoder SDK


ACD/ChemFolder Enterprise

Implement ACD/I-Lab: Intranet Edition, on single or multiple servers,

and access ACD/Labs’ prediction and database search services via

your enterprise’s intranet page or portal. You can submit your

structures in a number of electronic formats, obtain predictions,

search property databases, and use your own data to train the

prediction engines, as supported by ACD/Labs desktop software.

Advanced Chemistry Development, Inc. (ACD/Labs)

110 Yonge Street, 14th floor

Toronto, Ontario Canada M5C 1T4

Toll free phone (USA and Canada): 1-800-304-3988

Phone: 1(416) 368-3435

Fax: 1(416) 368-5596

General Information:[email protected]

Sales:[email protected]

[email protected]

[email protected]

Please review the list of distributors at

www.acdlabs.com/distributors/, or contact

ACD/Labs and we will put you in touch with

the appropriate distributor.

ACD/Labs has distributors in many countries throughout Europe, Asia, and Africa. Direct sales

are available for North America, UK, and a number of countries in the Asia-Pacific region.

Please note: Multinational companies may have global arrangements

with ACD/Labs directly. Please check with us first.

ACD/Labs Distributors

ACD/Labs Head Office

ACD/Labs Offices

System Requirements

Australia

Austria

Belgium

China

Croatia

Cyprus

Czech Republic

Denmark

Finland

France

Germany

Greece

Hungary

Israel

Italy

Japan

The Netherlands

Norway

Poland

Slovenia

South Africa

South Korea

Spain

Sweden

Switzerland

Canada France India Russia UK USA

Desktop Products

1. Pentium class processor with a clockrate of no less than 1 GHz.

2. Graphics adapter with a resolution of no less than 800 by 600 with 256 colors.

3. Disk space requirements can range from 10 to 1200 MB depending on themodules purchased.

4. A Microsoft® mouse or fully compatible pointing device.

5. Windows® 2000 SP4, or XP Professional SP2 with 128 MB or more of RAM.

acd/labs software for physical chemistryacd/chemsketch acd/pka accuracy extender display the...

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