User's Guide for the
Chemical Transformation Simulator
(CTS), Version 1.0
07/16/2019
Chemical Transformation Simulator:
A Cheminformatics Tool for Predicting
Transformation Pathways and Physicochemical
Properties
2019 U.S. Environmental Protection Agency
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NOTICE
This document has been reviewed by the U.S. Environmental Protection Agency, Office of Research and
Development, and approved for publication. It does not represent and should not be construed to
represent any Agency determination or policy. Mention of trade names or commercial products does
not constitute endorsement or recommendation for use.
Purpose
The Chemical Transformation Simulator (CTS) User's Guide is designed to provide the first-time user a
complete understanding of how to utilize the CTS tool. The User's Guide may be reviewed from start to
finish or by moving directly to a topic of interest through selection of the appropriate topic in the Table
of Contents.
Table of Contents
NOTICE 2
Purpose 2
Introduction 3
Background 3
Using the CTS Software 4
Restrictions 4
Accessing the CTS 4
CTS Modules Overview 6
Chemical Editor (CE) 6
Physicochemical Properties (PCP) Module 6
Reaction Pathway Simulator (RPS) 7
Execution of the CTS 10
Single Chemical Entry 10
Batch Chemical Entry 11
Execution of the CTS Workflows 12
Calculate Chemical Speciation Workflow 12
Calculate Ionization Constants 17
Calculate Dominant Tautomer Distribution 19
Calculate Stereoisomers 22
Calculate Physicochemical Properties Workflow 25
Generate Transformation Products Workflow 32
Reaction System Guidelines 35
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Generation of PDF, HTML and CSV Reports
References
45
47
Introduction
The Chemical Transformation Simulator (CTS) provides the calculated physicochemical
properties of a target chemical and its transformation products, which are predicted as a function
of the reaction system of interest. This is accomplished through the integration of
cheminformatics applications for the encoding of process science underlying transformation
pathways and computational chemistry tools for the calculation of physicochemical properties.
The CTS consists of three modules, the selection and order of execution of which is based on the
user's choice of one of three available workflows as described below.
• Chemical Editor (CE) Module: Provides options for chemical entry through SMILES
notation, chemical name, CAS #, or drawn structure, as well as speciation of the parent
chemical
• Physicochemical Properties (PCP) Module: Calculates physicochemical properties for
the parent chemical and predicted transformation products based on the executions of
multiple physicochemical calculators
• Reaction Pathway Simulator (RPS) Module: Generates potential transformation
products based on user-specified reaction conditions
Background
A key Agency need identified as a high priority in the Chemical Safety for Sustainability (CSS)
National Research Program is for high throughput computational systems to rank chemicals
based on hazards and risks. To fully characterize the risks associated with the release of a
chemical into the environment, tools are necessary to simulate environmental fate and transport
for organic chemicals for which such data are not available. Knowledge of inherent chemical
properties (ICP) is essential for the parameterization of environmental fate and transport models.
Of the -85,000 chemicals in the TSCA inventory, it is estimated that high quality measured ICP
data are available for less than 2% of these chemicals. Additionally, 20 to 30 new chemicals a
month are being assessed through the Office of Pollution Prevention and Toxics (OPPT) Pre-
Manufacturing Notification (PMN) process. This ever-growing data gap must be addressed
through the development of a high throughput computational system for calculating the ICP
necessary for the parameterization of environmental fate models used to estimate environmental
concentrations of both the parent chemical and predicted transformation products as a function of
environmental conditions.
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The key components of the CTS are the Physicochemical Properties module (PCP) and the
Reaction Pathway Simulator module (RPS). The PCP is based on a consensus approach that
allows the user to compare output generated by several calculators that take different approaches
to calculating specific physicochemical properties. These calculators include (1) EPI Suite,
which uses a fragment-based approach, (2) TEST (Toxicity Estimation Software Tool), which
uses Quantitative Structure Activity Relationship (QSAR)-based approaches, (3) ChemAxon
plug-in calculators, which use an atom-based fragment approach, and (4) OPERA (OPEn
structure-activity/property Relationship App), which uses a weighted k-nearest neighbor
approach to construct QSAR and Quantitative Structure Property Relationship (QSPR) models.
The output derived from these calculators will enable the user to compare the calculated data
with measured data in readily accessible web-based databases.
The output of the RPS is based on the selection and execution of reaction libraries that represent
one-step reactions for transformation (e.g., abiotic reduction and hydrolysis) of reactive
functional groups. These one-step reactions represent viable transformation pathways based on
the identification and subsequent transformation of reactive functional groups. A reaction library
for human phase I metabolism developed by ChemAxon is also available through the CTS. The
development of reaction libraries allows us to "encode" the known process science published
(current and future) in the peer-reviewed literature. The encoding of process science is
accomplished using Chemical Terms Language and Smart Reaction strings through
cheminformatics applications. The execution of these reaction libraries provides dominant
transformation pathways and products for the chemical of interest as a function of environmental
conditions.
Using the CTS Software
Restrictions
The CTS is designed to predict transformation pathways and calculate physicochemical
properties for organic chemicals. The CTS is designed for users with expertise regarding the
environmental processes controlling the degradation of organic chemicals and the use of
physicochemical properties in environmental fate modeling. Currently, organometallics, non-
dissociating salts of organic chemicals, and polymers are not recognized by the CTS. To provide
CTS users with a rich user experience we take advantage of features specified in the HTML 5
standards. Internet Explorer does not fully implement support for HTML 5 standards. As a
result, CTS functionality will be limited when using the Internet Explorer web browser. We
recommend using the latest version of Google Chrome or Mozilla Firefox.
Accessing the CTS
Currently users have access to the CTS through a password system. The CTS can be accessed
through https://qed.epacdx.net/ctsA which provides the models currently available on the web
Quantitative Exposure Domain (QED) as shown in the screen shot below.
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Quantitative Exposure Domain
public
epa internal
CSS Apps
SHC Apps
SSWR Apps
api documentation
source code
Environmental Models and Services
Chemical Transformation Simulator
The Chemical Transformation Simulator (CTS) provides the calculated physicochemical properties of the
parent chemical and transformation products, which are predicted as a function of the reaction system of
interest. This is accomplished through the integration of cheminformatics applications for the encoding
of process science underlying transformation pathways, computational chemistry tools for the
calculation of physicochemical properties, and software technologies that provide access to on-line
databases for environmental descriptors required for estimating environmental concentrations.
Hydrological Micro Services
Hydrological Micro Services (HMS) provides component and model data services relates to hydrology
(e.g., evapotranspiration, precipitation, surface runoff, subsurface flow, soil moisture, temperature) and
water quality (e.g., chemistry, eutrophication. mercury, microbes, nutrients, pH levels, sediment and
temperature).
pram: Pesticide risk assessment models
Pram is a cloud-based web application platform that includes a variety of aquatic, terrestrial and
atmospheric deposition fate and transport models used by the EPA for the ecological risk assessment of
pesticides. The science models in the iibertool provide predictions concerning chemical concentrations
in environmental media, exposure doses, tissue residues and ultimately predictions of effects. These
predictions are relevant for a number of ecological species under regulations that the EPA is responsible
for, including the registration of pesticides and the protection of endangered species.
CTS Homepage: The home page of the CTS is accessed by clicking on the CTS link. The home
page provides access to the CTS through the selection of one of three CTS workflows and
general information concerning the major modules of the CTS, the physicochemical calculators
and reaction libraries as shown in the screen shot below.
CTS: Chemical Transformation Simulator
About
CTS Home
AboutCTS
Execute CTS
Workflows
Calculate Chemical
Speciation
Calculate Physicochemical
Properties
Generate Transformation
Products
What is CTS?
Documentation
The Chemical Transformation Simulator (CTS) is a web-based tool for predicting environmental and
biological transformation pathways and physicochemical properties of organic chemicals.
CTS Workflows
Three workflows have been implemented in CTS to help users predict how organic chemicals are
partitioned, transformed and metabolized in environmental and biological systems. More information
about the individual workflows and modules is available under the tabs in the navigation panel.
Calculate Chemical Speciation Workflow: Calculates the speciation (i.e., ionization as a function of pH,
tautomer distribution, and possible stereoisomers) of the entered chemical.
Calculate Physicochemical Properties Workflow: Calculates physicochemical properties for the
entered chemical using four stand-alone calculators: EPI Suite, ChemAxon, TEST, and OPERA.
Download CTS User's Guide
(PDF)
CTS Modules
Physicochemical Calculators
Reaction Libraries
API Documentation
Manuscripts
Version History
Help
Generate Transformation Products Workflow: Generates transformation products of the entered
chemical based on user-specified conditions and reaction libraries. Once transformation products are
generated, physicochemical properties for one or more parent or product chemicals can be calculated
within the workflow.
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CTS Modules Overview
Chemical Editor (CE): CTS's Chemical Editor (CE) appears at the beginning of all workflows
and allows users to enter chemicals by their name, Chemical Abstracts Service Registry Number
(CAS#), Simplified Molecular-Input Line-Entry System (SMILES) string, or by drawing the
chemical's structure. ChemAxon's Marvin and JChem applications and EPA's CompTox
Chemistry Dashboard (https://comptox.epa.gov/dashboard) are used to generate a standardized
SMILES string, preferred common name, IUPAC name, chemical formula, relevant CAS
numbers, average and monoisotopic masses, and the DTXSID (unique substance identifier
assigned by EPA's National Center for Computational Toxicology (NCCT)) for the selected
chemical.
Chemical Speciation: CTS's Chemical Speciation (CS) workflow uses ChemAxon's Plugin
Calculators to generate:
• The speciation of a chemical as a function of pH;
• The ionization constant(s);
• The dominant tautomer distribution; and
• Structures for all possible isomers.
Physicochemical Properties (PCP) Module: CTS's Physicochemical Properties Module
calculates physicochemical properties for the parent chemical and predicted transformation
products based on the findings of multiple physicochemical calculators. The PCP is based on a
consensus approach that allows users to compare output from multiple calculators that use
different approaches to calculate specific physicochemical properties.
The calculators that PPC is currently accessing include:
1. EPI Suite, which uses a QSAR approach with either fragment counts or properties as
descriptors;
2. Toxicity Estimation Software Tool (TEST), which implements several approaches, including
fragment-based QSARs, hierarchical clustering with structural similarity based on a variety
of 2-D physicochemical descriptors, and nearest neighbor;
3. ChemAxon plug-in calculators, which are based on QSARs with either atom or fragment
counts as descriptors; and
4. OPEn structure activity/property Relationship App (OPERA), which uses a weighted k-
nearest neighbor approach to construct QSAR/QSPR models based on 2-D physicochemical
descriptors.
Users also have the option to request measured data that is available in the EPI Suite
PHYSPROP physicochemical property database. In addition, the geometric mean of the
predicted values (not including any measured data or ionization constants) for each selected
property from the selected calculators will be automatically calculated and displayed in the table
when predicted values are requested. Further information on the calculation of the geometric
mean is provided in the Physicochemical Properties Module section of this document.
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Reaction Pathway Simulator (RPS): CTS's Reaction Pathway Simulator (RPS) generates
potential transformation products based on user-specified reaction conditions. The output of the
RPS is based on the selection and execution of reaction libraries that represent reaction schemes
for the transformation of reactive functional groups that are susceptible to processes such as
reduction and hydrolysis. These reaction schemes denote viable transformation pathways based
on the identification and transformation of the reactive functional groups. A rank is assigned to
each one of the reaction schemes based on available experimental data. The rank is essentially a
relative reaction rate, defined on a scale of one to seven, with seven being assigned to the fastest
reaction schemes. The rank of each scheme is used to calculate an approximate percentage
production of each potential transformation product.
In Metabolizer, an algorithm has been implemented to approximate a percent production and
accumulation for products of each reaction scheme. In the Metabolizer algorithm, the unitless
"formation" value for scheme i (fi) is defined as the number 7 raised to the power of the rank:
y. i£f yRanki
The "formation" values are analogous to rate constants, and the "production" (in %) of the
product(s) generated by scheme i is calculated according to the following equation:
100 ft
0/ p. = 11
70 ri yN f
2->j=llj
where N is the total number of transformation schemes in the current generation. The
"accumulation" of the product formed by scheme i is then calculated as the difference between f,
and the summation of the formation values for all M schemes that may transform the product in
the next generation, normalized by the summation of the formation values for all transformation
schemes in the current generation:
, ioo(/,-sfl J,)
% At 555—7
A more detailed description of the production and accumulation calculations is provided in the
online documentation for the CTS Reaction Libraries.
Developing reaction libraries allows scientists to "encode" the known process science published
- current and future - in the peer-reviewed literature. Encoding process science is accomplished
by using Chemical Terms Language and cheminformatics applications. Reaction libraries have
been developed for the environmental transformation processes of abiotic hydrolysis and abiotic
reduction. A reaction library for human phase I metabolism that was developed by ChemAxon is
also available through the RPS.
Executing these reaction libraries provides dominant transformation pathways and products for
the chemical of interest as a function of environmental conditions. Users also have the option to
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execute the PCP for the calculation of physicochemical properties for the parent chemical and
transformation products.
Links to the process science supporting the currently available reaction libraries are also
available. For example, clicking on the Reaction Libraries tab, followed by clicking "Click here
to download the abiotic hydrolysis library" as shown in the screen shot below.
^^Tbioti^ydralysis Reaction Library
1 Version 1.6 of the Abiotic Hydrolysis Reaction Library contains 25 reaction schemes; l
¦ Haloeenated Aliohatics: Nucleoohilic Substitution
• Lactam Hvdrolvsis
Scheme A: C-X with no other adjacent halogens
o Scheme B: C-X with vicinal halogen atoms
Scheme C: C-X with geminal halogen atoms
• Haloeenated Aliohati-cs: Elimination
• Eooxide Hvdrolvsis
• OreanoDhosohorus Ester Hvdrolvsis 1 iBase-Catalvzed)
¦ OraarioohosDhorns Ester Hvdrolvsis 2 (Neutral or Acid-Catafvzedl
¦ Carboxvlic Acid Ester Hvdrolvsis
• Lactone Hvdrolvsis
« Carbonate Hvdrolvsis
• Cyclic Carbonate Hvdrolvsis
» Carbamate Hvdrolvsis
• Urea Hvdrolvsis
• Cvclic Urea Hvdrolvsis
• Sulfonylurea Hvdrolvsis
• Thioearbaniate Hvdrolvsis
• Nitrite Hvdrolvsis
• N-S Cleavage
» Imide Hvdrolvsis
» Acid Halide Hvdrolvsis
» Dehydration of Geminal Oiols
• Anhydride Hvdrolvsis
• Cvclic Anhydride Hvdrolvsis
• Amide Hvdrolvsis
Selection of one of the transformation pathways provides the reaction scheme, and documented
examples with references. The following illustrates this information for Epoxide Hydrolysis:
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EXAMPLES:
• 1,2-Epoxycyclohexane (McMurry, 2011)
• Endrin (Larsen arid Weber, 1994; U.S. EPA, 1992)
CI
• l,2-Epoxy-l,2,3,4-tetrahydronaphthalene (Becker ef al,
1979)
Epichlorohydrin (Gaca etal, 2011)
CL
SCHEME
H H
1 1
6
1 1
Oi 0
ZA -
—*-
2(A) 3, (A)
2:(A) 3(A)
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Execution of the CTS
The CTS is executed by selecting one of three available workflows (see descriptions below) and
by entering a single chemical or by batch mode. The process for entering a single chemical or by
batch, as described below, is identical for each of the workflows.
Single Chemical Entry
For single chemical entry, the "Run single chemical" tab is selected below the workflow of
interest in the left-hand frame. The Chemical Editor appears where there is the option to either
enter a SMILES String, name, or Chemistry Abstracts Service (CAS) # in the Lookup Chemical
box, or to draw a chemical structure using the Chemical Editor (see screen shot below). For
either case, the appropriate box must be clicked after providing the required information. Details
concerning the use of the chemical editor can be found at
https://docs.chemaxon.com/displav/docs/MarvinSketch.
CTS: Chemical Transformation Simulator
Calculate Chemical Speciation
Chemical Editor | Chemical Speciation
Execute CTS
Workflows
Calculate Chemical
Speciation
Run single chemical
Run batch file
Calculate Physicochemical
Properties
Generate Transformation
Products
Documentation
Download CTS User's Guide
(PDF)
Physicochemical Calculators
Reaction Libraries
API Documentation
Manuscripts
Version History
Help
Enter a SMILES, Name, or CAS#, or draw a chemical, then click the button located in the top right of the chosen method to get results,
dickthe "next" burton below or click the "Chemical Speciation* link above to continue through the workflow.
Lookup Chemical
Enter a SMILES, Name, or CAS# and Click Here
Draw Chemical Structure
Draw a chemical structure and Click Here
qiei x ® cs <$. q. ®. r h: © a
U
poooo
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Batch Chemical Entry
For batch chemical entry, the "Run batch file" tab is selected below the workflow of interest in
the left-side frame. By clicking on the sample batch input link, the example batch file, shown
below in the screen shot, is opened or downloaded. The chemicals are entered as a single
column of SMILES strings. The default value is currently set to a maximum of 10 chemicals.
Sample batch input:
ci=cc=oc=ci
cc (=03 oci=cc=cc=cic coj =o
oci=cc=cc=ei
QC (=0} CC (O] (CC (O] =0} C (O] =o
[O-] [N+] t=Q] C1=CC=C (C=C1 J [N+] ( [O-] ] =0
CTS: Chemical Transformation Simulator
CTS Home
About CTS
Execute CTS
Workflows
Calculate Chemical
Speciation
Run single chemical
Run batch file
Calculate Physicochemical
Properties
Generate Transformation
Products
Documentation
Download CTS User's Guide
(PDF)
CTS Modules
Physicochemical Calculators
Reaction Libraries
API Documentation
Manuscripts
Version History
Help
Calculate Chemical Speciation Batch Run
• Upload a text file of SMILES strings organized into a single column (View/download sample batch input
file):
File to upload: Choose File I No file chosen
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Execution of the CTS Workflows
The user executes the CTS through the selection of one of three available workflows:
• Calculate Chemical Speciation
• Calculate Physicochemical Properties
• Generate Transformation Products
Calculate Chemical Speciation Workflow
Selection of the Calculate Chemical Speciation Workflow provides this page illustrating the
workflow overview as illustrated below. ChemAxon calculator plugins are executed for the
calculation of chemical speciation.
CTS: Chemical Transformation Simulator |
1 About
Calculate Chemical Speciation
CTS Home
Overview
About CTS
Execute CTS
Workflows
This workflow allows you to enter an individual chemical through the Chemical Editor {see below). Based
on the selection of the available options for structure analysis, you will be able to generate structure
information including ionization constants {pKa values), the dominant forms of ionized species and
Calculate Chemical
Speciation
tautomers, as well as structures for possible stereoisomers.
Run single chemical
Run batch file
Calculate Physicochemical
Properties
Piolonation.
Generate Transformation
Products
- pKa calculator!
- Microspedes
disirtoution
1 Documentation
Download CTS User's Guide
(PDF!
Chemical Edrtor
CTS Modules
__
Physicochemical Calculators
steroisomer
Generation
Reaction Libraries
API Documentation
Manuscripts
Version History
Help
12
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Clicking on the "Run single chemical" link takes the user to the Chemical Editor. For the
following example, 4-aminophenol was entered into the Chemical Editor as shown in the screen
shot below.
Draw Chemical Structure
Draw a chemical structure and Click Here
d oi y o x ® dj ©» ©* ®»
¦-Y
<5>
/
[3
m
-ft- h± ® a
Nhi
OH
9 a o o o
H
c
N
0
S
F
P
CI
Br
1
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After clicking the Next button at the bottom of the Chemical Editor or the Chemical Speciation
link at the top of the workflow frame, select from three available options for calculating chemical
speciation as shown in the screen shot below.
Calculate Chemical Speciation
Chemical Editor | Chemical Speciation
Oisck ofs or,Tore caicaiatfov methods to run, tfrsr hrt submit beiow
Calculate Ionization Constants (pKa) Parameters
Number of decimals for pKa:
pH Lower Limit; jo
pH Upper Limit; |i4
pH Step Size; jo.2
Generate Major Microspecies at pH: 7.0
Isoelectric Point (pi)
0.5
pH Step Size for Charge Distribution:
Calculate Dominant Tautomer Distribution
Maximum Number of Structures: [100
at pH:
7.0
Caku late Stereoisomers
Maximum Number of Structures: 100
Defaults
Clear
Back
Submit
Select any combination of the calculators; use the provided default values or change the default
values required by the user. The following parameters can be adjusted:
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• Calculate Ionization Constants
- Number of decimals: Number of decimal places calculated for acidic and basic pKa
values
- pH Lower limit: Specifies the lower end of the pH range for which the microspecies will
be generated
- pH Upper limit: Specifies the upper end of the pH range for which the microspecies will
be generated
- Generate Major Microspecies at pH: Generates the Major Microspecies at the specified
pH.
- pH step size: Specifies the pH step size for the X-Axis of the plot illustrating the
distribution of the microspecies as a function of pH
- Isoelectric Point (pi) pH Step Size for Charge Distribution: Specifies the pH step size
for the X-Axis of the plot illustrating the Isoelectric Point and charge distribution as a
function of pH
• Calculate Dominant Tautomer Distribution
- Maximum Number of Structures: Specifies the maximum number of structures that will
be generated.
- At pH: Specifies the pH at which the dominant tautomer distribution will be calculated
• Calculate Stereoisomers
- Maximum Number of Structures: Specifies the maximum number of structures that will
be generated.
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The user also has the option of running a batch file. By clicking on the "Run batch file link", the
following screen appears. The user has the option to view or download a sample batch input file
or enter a file by clicking on the Choose File button.
CTS: Chemical Transformation Simulator
CTS Home
About CTS
Execute CTS
Workflows
Calculate Chemical
Speciation
Run singie chemical
Run batch file
Calculate Physicochemical
Properties
Generate Transformation
Products
Calculate Chemical Speciation Batch Run
• Upload a text file of SMILES strings organized into a single column (View/download sample batch input
file):
File to upload: Choose File I No file chosen
Documentation
Download CTS User's Guide
(PDF)
CTS Modules
Physicochemical Calculators
Reaction Libraries
API Documentation
Manuscripts
Version History
Help
16
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Calculate Ionization Constants
Once the calculator(s) has been chosen and the appropriate parameters entered, click the Submit
button to view the results. The calculator for ionization constants has been chosen for this
demonstration as shown in the screen shot below.
Inputs: The molecular information and ionization parameters provided by the user.
Calculate Chemical Speciation
Chemical Editor | Chemical Speciation
Check one or more calculation methods to run, then hit submit below
Calculate Ionization Constants (pKa) Parameters
Number of decimals for pKa: 2
pH Lower Limit: o
pH Upper Limit: 14
pH Step Size: |o.2
Generate Major Microspecies at pH: |7.0
Isoelectric Point (pi)
pH Step Size for Charge Distribution:
The results of the ionization constant calculation are illustrated in the screen shots below:
• pKa Calculations: Provides the chemical structure entered, the generated
microspecies, and the distribution of microspecies as a function of pH over the pH
range specified. Results are color coded.
• Isoelectric Point: The isoelectric point is provided as well as a graph illustrating the
charge on the chemical as a function of pH.
• Major Microspecies: The dominant microspecies formed at the pH selected.
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" Results
- pKa
Basic pKa Value(s): [5.43]
Acidic pKa Value(s): [10.4]
Isoelectric Point = 7.92
Microspecies
Parent
Microspecies Distribution (%)
Major Microspecies at pH: 7.0
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Calculate Dominant Tautomer Distribution
The CTS uses ChemAxon's tautomerization engine for the calculation of the dominant tautomer
distribution. For this demonstration, l-phenylbutane-l,3-dione has been entered into the
Chemical Editor as shown in the screen shot below.
Lookup Chemical
Enter a SMILES, Name, or CAS# and Click Here
l-phenylbutane-l,3-dione
/,
Draw Chemical Structure
Draw a chemical structure and Click Here
Daia ") X (Si ts <3, ®l 42 -ft- © ©
O
/
J
ii
90000
H
C
N
0
S
F
P
CI
Br
1
Results
Entered Chemical
l-phenylbutane-l,3-drone
Initial SMILES
CC (=0}CC(=0) C 1=CC=CC=C1
Standardized SMILES
CC(=0)CC(=O)Cl=CC=CC=Ci
19
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Clicking the Next button brings up the Calculate Chemical Speciation Workflow Inputs page.
After selecting the Calculate Dominant Tautomer Distribution option, enter a limit for the
number of possible tautomers and the pH value for which the distribution will be calculated. The
default values are pH 7.0 and a limit of 100 tautomers as shown in the screen shot below.
Calculate Ionization Constants (pKa) Parameters
Number of decimals for pKa:
pH Lower Limit:
pH Upper Limit:
pH Step Size:
14
0.2
Generate Major Microspecies at pH:
Isoelectric Point (pi)
pH Step Size for Charge Distribution:
7.0
0.5
Calculate Dominant Tautomer Distribution
Maximum Number of Structures:
100
at pH:
7.0
Calculate Stereoisomers
Maximum Number of Structures:
100
Defaults I Clear
Back Submit
20
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Click on the Submit button to view the output page for the tautomerization distribution based on
the user-defined values.
The Output screen shows the User Inputs (see screen shot above) as well as the tautomer
distribution for the chemical of interest (see screen shot below). The individual structures can be
enlarged by placing the cursor on top of the structure. The molecular information including the
formula, IUPAC name, mass and SMILES string is also provided.
- Results
- Tautomerization (pH = 7.0)
Percent Dist: 64.4% Percent Dist: 34.34% Percent Dist: 0.22% Percent Dist: 0.22%
Ox ^.CHj H3C. 0"
.0 0
Percent Dist: 0.21% Percent Dist: 0.1%
HCf .0 HO
til
21
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Calculate Stereoisomers
For this demonstration, 1,2,3,4,5,6-hexabromocyclohexane has been entered into the Chemical
Editor as shown in the screen shot below.
Draw Chemical Structure
Draw a chemical structure and Click Here
D ol ~ O
n U O O 0
22
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Calculate Ionization Constants (pKa) Parameters
Number of decimals for pKa: 2
pH Lower Limit: 0
pH Upper Limit: 14
pH Step Size: 0.2
Generate Major Microspecies at pH: 7.0
Isoelectric Point (pi)
pH Step Size for Charge Distribution:
0.5
Calculate Dominant Tautonier Distribution
Maximum Number of Structures: 100
at pH: j7.0
if Calculate Stereoisomers
Maximum Number of Structures: 100
Defaults
Clear
Back
Submit
After selecting the Calculate Stereoisomers option, enter a limit for the maximum number of
possible stereoisomers. The default value is 100 stereoisomers as shown in the screen shot
above.
Clicking on the Next button provides the results of the calculation, which il lustrate that
1,2,3,4,5,6-hexabromocyclohexane can exist as nine different stereo isomers as shown in the
screen shot below. The individual structures can be enlarged by placing the cursor over the
structure. The molecular information including the formula, IUPAC name, mass and SMILES
string is also provided.
23
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Results
Stereoisomers (9)
Br
Br
Br.
Br Br
Br
"»/.
Br
Br
Br
Vr*B'
Br^V'X^/'^Br
Br
Br
Br,
Br
Br
Vs
Br Brx
'Br
Br
Br
Br
Br
BrV^A.>Br Brv^\.^Br
Br^ ""^^Br
Molecular Information
sm-|ec BrtC@@H]1[C@H](Br)[C@H](Br)
[C@H](Br)[C@H](Br)[C@@H]1 Br
exactMass 551.556978 g/mol
• (1 R.2R.35,45,5sf6s)-1,2,3,4,5,6-
hexa bro mocydohexa ne
mass 557.538 g/mol
formula C6H6Br6
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Calculate Physicochemical Properties Workflow
Selection of the Calculate Physicochemical Properties Workflow provides the screen shot below
illustrating the workflow overview. Click on the "Run single chemical" link to submit a single
chemical for processing, or click on the "Run batch file" link to submit a batch file.
CTS: Chemical Transformation Simulator
About
CTS Home
AboutCTS
Execute CTS
Workflows
Calculate Chemical
Speciation
Calculate Physicochemical
Properties
Run single chemical
Run batch file
Generate Transformation
Products
Documentation
Download CTS User's Guide
(PDF)
CTS Modules
Physicochemical Calculators
Reaction Libraries
API Documentation
Manuscripts
Calculate Physicochemical
Properties Overview
This workflow allows you to enter an individual chemical through the Chemical Editor (see below) or
through batch mode (select Batch tab). Based on your selection of the available physicochemical
calculators and physicochemical properties, you will be able to generate calculated physicochemical
properties of interest.
Chemical Fditor
V
Select
Physicochemical
Calculators
Physicochemical
Properties
Calculator
Select
Physicochemical
Properties
Version History
Help
25
-------
For this demonstration, l-methoxy-2,4-dinitrobenzene has been entered into the Chemical
Editor. The results are shown in the screen shots below. Select the Next button to choose the
physiochemical calculators and physicochemical properties of interest.
CTS: Chemical Transformation Simulator
CTS Home
AboutCTS
Execute CTS
Workflows
Calculate Chemical
Speciation
Calculate Physicochemical
Properties
Run single chemical
Run batch file
Ge n e rate Transformation
Products
Documentation
Download CTS User's Guide
(PDF)
CTS Modules
Physicochemical Calculators
Reaction Libraries
API Documentation
Manuscripts
Version History
Help
Calculate Physicochemical Properties
Chemical Editor | Physicochemical Calculators
Enter a SMILES, Name, or CAS#, or draw a chemical, then click the button located in the top right of the chosen method to get results.
Click the "next" button below or click the "Physicochemical Calculators" link abowe to continue through the workflow.
Lookup Chemical
Enter a SMILES, Name, or CAS# and Click Here
l-methoxy-2,4-dinitrobenzene
Draw Chemical Structure
Draw a chemical structure and Click Here
D 6 § ") x ffl ©. ©. 4= ^ <§> a
!!..!!!
-------
Results
Entered Chemical
l-methoxy-2,4-d [nitrobenzene
Initial SMILES
COC1=CC=C(C=C1[N+]([0-])=0)[N+]
([o-])=o .
Standardized SMILES
C0Cl=CC=C(C=Cl[N+]([0-])=0)[N+]
(to-])=o '
Preferred Name
2,4-Dinitroanisole
A
IUPAC
l-methoxy-2,4-di nitrobenzene
Formula
C7H6N205
Preferred CAS
119-27-7
Associated CAS
119-27-7
DTXSID
DTXSID9041366
Average Mass (g/mol)
198.134
Monoisotopic Mass (g/mol)
198.027671301
A
27
-------
Use the Calculate Physicochemical Properties Workflow Inputs screen to select physicochemical
properties and the physicochemical calculators of interest as shown in the screen shot below.
Selection of the All button for the physicochemical properties selects all properties no matter
which calculators are chosen, although only the available properties from each calculator will be
calculated. See Table 1 for a summary of the calculators and calculation methods used in the
Physicochemical Properties Calculator.
CTS Home
About CIS
Execute CTS
Workflows
Calculate Chemical
Speciation
Calculate Physicochemical
Properties
Run single chemical
Run batch file
Generate Transformation
Products
Documentation
Download CTS User's Guide
(PDF)
CTS Modules
Physicochemical Calculators
Reaction Libraries
API Documentation
Manuscripts
Version History
Help
Calculate Physicochemical Properties
Chemical Editor j Physicochemical Calculators
Check chemical properties and which calculators to compute them, then hit submit
~ All
Neutral Species
Inputs:
^t Melting Point (°C)
~ Boiling Point (°C)
it Water Solubility (mg/L)
Vapor Pressure (mmHg)
it Ionization Constant
^t Henry's Law Constant (atm-
m3/mol)
it Octanol/Water Partition
Coefficient (log)
^t Organic Carbon Partition
Coefficient (log(L/kg))
Bioconcentration Factor
(log(L/kg))
Bioaccumulation Factor
(log(L/kg)}
pH-Dependeiit Inputs
at pH: 7.0
it Octanol/Water Distribution
Coefficient (log)
it Water Solubility (mg/L)
~
0
K
Geometric
l<
ChemAxon
EPI Suite
TEST
OPERA
Mean
Measured
Available
Unavailable
Back Submit
28
-------
Application
or Website
Version
Model
Property
Calculation Method
References
ChemAxon
Plugin
Calculators
16.10.31.0
KLOP
Kow, Dow
Group Contribution: MLR with
fragment counts as descriptors
Klopman et al. (1994)
VG
Kow, Dow
Group Contribution: MLR with
fragment counts as descriptors
Viswanadhan et al. (1989)
PHYS
Kow, Dow
Group Contribution: MLR with
fragment counts as descriptors
Based on Viswanadhan et al.
(1989) with PHYSPROP as
training set
Solubility
Predictor
WS
Group Contribution: MLR with
atom counts as descriptors
Hou et al. (2004)
pKa Predictor
pKa
Ionization site-specific regression
equations
Szegezdi and Csizmadia
(2004,2007)
EPI Suite
4.11
KOWWIN™
Kow
Group Contribution: MLR with
fragment counts as descriptors
Meylan and Howard (1995)
WATERNT
WS
Group Contribution: MLR with
fragment counts as descriptors
US EPA (2012)
WSKOW
WS
MLR with log Kow, MP and MW
as descriptors
Meylan et al. (1996); US EPA
(2012)
KOCWIN
Koc
MCI-based QSAR;
MLR with log Kow as descriptor
Meylan et al. (1992)
MPBPVP
MP, BP,
VP
Group Contribution: MLR with
fragment counts as descriptors for
MP and BP; VP from nonlinear
function of BP
US EPA (2012)
HENRY WIN
HLC
Bond Contribution: MLR with
bond counts as descriptors
US EPA (2012)
BCFBAF™
BCF and
BAF
MLR with log Kow as descriptor;
Arnot-Gobas method using upper
trophic values
US EPA (2012)
TEST.
4.2
FDA
MP, BP,
WS, VP,
BCF
Hierarchical Clustering with
similar chemicals
Contrera et al. (2003);
Martin et al. (2008)
Group
Contribution
MP, BP,
WS, VP,
BCF
Group Contribution: MLR with
fragment counts as descriptors
Martin and Young
(2001)
Hierarchical
Clustering
MP, BP,
WS, VP,
BCF
Hierarchical Clustering
Martin et al. (2008)
Nearest
Neighbor
MP, BP,
WS, VP,
BCF
Average property value for 3 most
similar molecules based on cosine
similarity coefficient
Martin et al. (2008);
U.S. EPA (2016)
OPERA
2.1
N/A
MP, BP,
WS, VP,
pKa, HLC,
Kow, Koc,
BCF, Dow
Weighted k-nearest neighbor
using 2D descriptors from PaDEL
Mansouri et al. (2018)
Table 1. Summary of the calculators and calculation methods used in the Physicochemical
Properties module.
29
-------
After selection of the physicochemical properties and calculators, selection of the Calculate data
button provides the physicochemical properties output as illustrated in the screen shots below.
Selection of the Measured checkbox provides available experimental data from the PHYSPROP
database.
A database of pre-calculated values from the OPERA calculator for several thousand common
chemicals has been implemented to improve the speed of retrieval from OPERA. If the given
chemical is not in the pre-calculated database, the OPERA calculator will run the models on the
fly, causing slower retrieval times for OPERA values.
The geometric mean of the predicted values (not including any measured data or ionization
constants) for each selected property from the selected calculators will be automatically
calculated and displayed under the Geometric Mean column when predicted values are
requested. For some chemicals, the value of the melting point and/or boiling point predicted by
one or more of the calculators may be a negative value in units of Celsius. Therefore, to calculate
the geometric mean of melting point and boiling point, the calculated values are converted from
degrees Celsius to Kelvin before calculating the geometric mean and converting that value back
to degrees Celsius.
Calculate Physicochemical Properties Output
Calculate Physicochemical Properties
Tuesday, 2019-July-02 15:55:27 (EST)
- User Inputs
Molecular Information
Entered chemical l-methojcy-2,4-dinitroben;ene
Initial SMILES COCl=CC=C[C=Cl[N+][[O-])=O)[N+H[O-])=0
Standardized SMILES COCl=CC=C(C=Cl[N+]([O-])=0)[N+]{[O-])=0
IUPAC l-nnethoJty-2,4-dinitroben2ene
Formula C7H6N205
CASs 119-27-7
Average Mass 198.134
Monoisotopic Mass 198.027671301
30
-------
Physic ochemkal Properties Results
Geometric
ChemAxon
EPI Suite
TEST
OPERA
Mean
Measured
AL!
Neutral Species
Inputs:
78JDHC
Melting Point (SCJ
9636
3730 NN
SOJ3O0C
95.09
87.45
9430
28630 WC
Boiling Point (=CJ
319.62
300.70 MN
315.00 QC
304.17
306.68
206.00
3.08e+2
Water Solubility (mg/L)
2,68e+2
WSKOW
233e+2
3J£le+2
2_33e+2
LSe+2
WATEIWfT
5J4e+2
QC
Vapor Pressure (mmHg)
l_38e-4
2.06e-4
HC
J_14e-4
NN
2J.7e-4
0C
3.G5t4
i_85e-4
N/A
Ionization Constant
none
25
Henry's Law Constant
(ati7wn3/mol)
4J6e-9
532e-7
523e-8
N/A
Ocfcanol/Water Partition
Coefficient (log)
L74KLOP
1.70 ve
L65 PKYS
171
L94
1.75
N/A
Organic Ca rbon Partition
Coefficient (log{L/kg))
236 MQ
2J37 KOW
? "re
2JS2
0.73 SM
Bioconcentration Factor
0.50 REG
OjLOHC
0.98
n Rfl
matWfcg))
0.68 A-G
CL4SNN
0.96 GC
¦J. DO
Bioaccu mutation Factor
(logfL/kg))
0.68 A-G
0.68
pH-Dependent
Inputs at pH: 7.0
Octanol/Water
1.74 KLOP
Distribution Coefficient
1_70 VQ
136
1.66
(l°8l
1_65 PHYS
Water Solubility (mg/L.)
-2_87e+S
-2_87e+3
Available
Jnovaftufote
Cancel I dear data Calculate data
31
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Generate Transformation Products Workflow
Selection of the Generate Transformation Products Workflow provides the screen shot below
illustrating the workflow overview. Click on the "Run single chemical" link to submit a single
chemical for processing, or click on the "Run batch file" link to submit a batch file.
CTS Home
About CTS
Execute CTS
Workflows
Calculate Chemical
Speciation
Calculate Physicochemical
Properties
Generate Transformation
Products
Run single chemical
Run batch file
Documentation
Download CTS User's Guide
{PDF)
CTS Modules
Physicochemical Calculators
Reaction Libraries
API Documentation
Manuscripts
Version History
Help
Generate Transformation Products
Overview
This workflow allows you to predict transformation products based on the selection and execution of the
reaction libraries that encode the process science for transformation processes. You have the option to
enter an individual chemical through the Chemical Editor or through batch mode (select Batch tab).
Entering the Reaction Pathway Simulator will allow you to select your reaction library of interest based
on your selection of reaction conditions.
Chemical Editor
i
Define
Reaction
Conditions
Reaction
Pathway
Simulator
T
Select
Reaction
Libraries
Physicochemical
Properties
Calculator
32
-------
For this demonstration, hexachloroethane has been entered into the Chemical Editor as illustrated
in the screen shot below.
Draw Chemical Structure
Draw a chemical structure and Click Here
D d 0 *3 X (5 QJ ©, ©, ®, -P -ft- Hi © a
<9
/
H
c
N
CI
o
CI
CI
CI
¦CI
p
CI
CI
Br
A
g a o o o
The first required input is the selection of one or more reaction libraries based on the
transformation pathways of interest. Three reaction libraries, including abiotic hydrolysis,
abiotic reduction and human phase I metabolism, are currently available in CTS. Reaction
libraries for photolysis and anaerobic biodegradation are currently under development, and a
seamless linkage to a reaction library for aerobic biodegradation will be available in the next
version of the CTS. There are available options for the selection of one or multiple reaction
libraries (see screen shot below):
• Reaction System Conditions
• OCSPP Harmonized Test Guidelines
• User Selected (Advanced)
The OCSPP Harmonized Test Guidelines specify EPA/OECD-recommended methods to
generate data that is submitted to EPA to support:
• The registration of a pesticide under the Federal Insecticide, Fungicide and Rodenticide
Act (FIFRA);
• The decision-making process supporting potential regulation of an industrial chemical
under the Toxic Substances Control Act (TSCA)
33
-------
Options for selecting Reaction Libraries
Reaction System Guidelines ( )OC5PP Guidelines (J User selected (advanced)
Reaction Libraries
Abiotic Hydrolysis
Aerobic Biodegradation
P hotolysis
Abiotic Reduction
Anaerobic Biodegradation
Human Phase 1 Metabolism
Reaction Options
Max n umber of senerations:
Clear
Selection of the Reaction System Conditions provides two options for reaction systems:
Environmental or Mammalian.
Selection of the Environmental Reaction System provides the option to select respiration type:
Aerobic or Anaerobic.
Selection of anaerobic respiration opens the window with the reaction libraries selected for the
transformation pathways that are currently available and will potentially occur under these
reaction conditions, which includes abiotic hydrolysis and abiotic reduction (see screen shot
below).
34
-------
• Reaction System Guidelines
Options for selecting Reaction Libraries
OCSPP Guidelines User selected (advanced)
• Environmental
Reaction system
Mammalian
| Anaerobic T
Select a respiration type
Reaction Libraries
Abiotic Hydrolysis
Aerobic 3iodegradation
Photolysis
0
Abiotic Reduction
Anaerobic Biodegradation
Human Phase 1 Metabolism
Reaction Options
Max number of generations: 2 T
Back
Selection of aerobic respiration opens the window with the reactions libraries selected that are
currently available and will potentially occur under these conditions, which currently includes
only abiotic hydrolysis.
Reaction System Guidelines
Selection of Reaction System Guidelines
Selection of mammalian reaction systems opens the window with the human phase I metabolism
reaction library selected as shown in the screen shot below. This is the only option available for
the mammalian reaction system.
35
-------
Options for selecting Reaction Libraries
• Reaction System Guidelines 0C5PP Guidelines User selected (advanced)
Environmental
Reaction system
• Mammalian
Reaction Libraries
Abiotic Hydrolysis
Aerobic 3iodegradation
Photolysis
Abiotic deduction
Anaerobic Siodegradation
if Human Phase 1 Metabolism
Reaction Options
IVa:
-------
Options for selecting Reaction Libraries
f Reaction System Guidelines 1 • jOCSPP Guidelines f User selected (advanced)
OECD Selection
• Fate. Transport, and Transformation (Series 835) Health Effects {Series 870}
Fate, Transport, and Transformation
Laboratory Abiotic Transformation Guidelines T
Reaction Libraries
Abiotic Hydrolysis
Aerobic Siodegradatton
Photolysis
Abiotic Reduction
Anaerobic Biodegradation
Human Phase 1 Metabolism
Reaction Options
Max number of generations: |_2 ~
Back Submit
37
-------
Selection of Health Effects provides one option for selection of a reaction library (i.e., Human
Phase I Metabolism) as shown in the screen shot below.
Choose Reaction System Description's or OCSPP "est Guidelines ft; help guide the selection of th-e appropriate reaction libraries, or
cnocse User Selection to manually select the reaction libraries to use for generating transformation products. Then set the Reaction
Options and dick submit.
Options for selecting Reaction Libraries
Reaction System Guidelines • OCSPP Guidelines Use reelected (advanced)
OECD Selection
Fate. Transport, and Transformation (Series 835)
• Health Effects (Series S70)
Reaction Libraries
Abiotic Hydrolysis
Aerobic Bio degradation
Photolysis
Abiotic Reduction
Anaerobic Biodegradation
Human Phase 1 Metabolism
Reaction Options
Max number of generations: |2 ~
Clear Back
38
-------
The third option for the selection of reaction libraries is through the selection of the "User
selected" button as shown in the screen shot below. This option provides the ability to select
amongst the currently available reaction libraries. After selecting reaction libraries through one
of the three options, the option to change the Reaction Options is given:
• Max number of generations: the maximum number of generations of transformation
products that will be generated. The default value is set at one, and the maximum value
is four.
Options for selecting Reaction Libraries
Reaction System Guidelines OCSPP Guidelines • User selected (advanced)
Reaction Libraries
Abiotic Hydrotysis
Aerobic Biodegradation
Photolysis
if Abiotic Reduction
Anaerobic Biodegradation
Human Phase 1 Metabolism
Reaction Options
Max number of generations:
Clear
2 »
Back Submit
After selection of the reaction libraries and reaction opti ons have been made, click the Submit
button to generate transformation products. The screen shot below summarizes the input data
and provides the first generation of transformation products (the default value) based on
execution of the abiotic hydrolysis and reduction libraries as previously selected.
39
-------
Generate Transformation Products Output
Generate Transformation Products
Wednesday, 2018-June-06 09:06:39 (EST)
- User Inputs
Molecular Information
Entered chemical hexachloroethane
Standardized SMILES ClC(ClMCl)C(Cl)(Cl)Cl
Initial SM8LES CtC(Cl)(Cl)C(Cl){Cl)Cl
IUPAC hexachloroethane
Formula C2C16
CAS rf €7-72-1
Average Mass 236.72 g/'mol
Monoisotopic Mass 233.8131162 g/mol
Reaction Pathway Simulator
Libraries abiotic_reduccion
Generation Limit 2
• Select (right click) a product in the tree below to view its molecular information.
• Left click a product in the tree below to view its transformation product and formation
pathway.
• Pan reaction pathways tree by holding down the left click button anywhere in the blue
area and moving the mouse.
• Zoom in and out with the mouse wheel.
Display up to:
2nd gen T
Total Products:6
+ View Molecular Information
+ Calculate Physicochemical Properties
40
-------
The number of viewed generations can be increased by changing the number of generations in
the "Display up to" window shown in the screen shot above. The screen shot below on the left
illustrates the reaction pathway map for the formation of one generation of products. The screen
shot below on the right illustrates the reaction pathway map for the formation of two generation
of products. Note, that the number of observed generations cannot exceed the Generation Limit
set on the previous screen. The screen shot above indicates the total number of products that are
predicted. If the total product = 0, then the user is to assume the selected reaction process does
not occur for the parent chemical of interest.
By placing the cursor over a product, a popup box appears, with a molecule number that signifies
its place in the reaction pathway map. For this example, tetrachloroethane (1.1.2) is the 2nd
product formed in the second generation from the 1st product (i.e., pentachloroethane, 1.1),
which was formed in the first generation from hexachloroethane as shown in the screen shot
below. Below the molecule number are values for production, accumulation, global
accumulation, and likelihood. The production, accumulation, and global accumulation values are
explained in detail in a separate document. Metabolites considered "likely" (having a global
accumulation of at least 10%) will be highlighted with a blue border in the tree.
By left-clicking on a product in the reaction pathway map, the next generation of transformation
products that are predicted to form from a selected product, as well as the reactions that form
them, are displayed under the reaction pathway map, as shown in the screen shot below. For each
step in the transformation sequence, the name of the reaction scheme that generated the product
is provided above the arrow between the parent and product. Clicking on a transformation
41
-------
scheme name opens a new browser tab with detailed information about the scheme from the
Reaction Library documentation. By right-clicking on a product, the molecular and metabolite
information for the product is displayed above the reaction pathway map. The selected
metabolite will be highlighted with a red border in the tree, as shown in the screenshot below.
The "Get transformation products" button immediately below the molecular information box can
be clicked to open a new browser tab with the product entered as the chemical of interest in the
Generate Transformation Products workflow.
Calculate Physicochemical Properties
molecule 1
Hydrogenolyss Cl-
~
ci a
molecule 1.1
CI
\
HydrogenoLysi:
V-c.
a—(
\
CI
molecule 1.1.2
generation: molecule 1.1.2
smiles: ClC(Ci)C(Cl)Cl
production: 16.67%
accumulation: 0.00%
global accumulation: 0.00%
likelihood: UNLIKELY
CI
V
-CI
a \
\
CI
Below the Molecular Information table, clicking on the Calculate Physicochemical Properties
dropdown box provides the various options for physicochemical properties and calculators to be
applied to the selected transformation product, as shown in the screen shots below.
42
-------
The selected physicochemical properties will be calculated and displayed in the results table.
For example, selection of the All and ChemAxon, EPI Suite, TEST and OPERA buttons and
Clicking on the Calculate Physicochemical Properties link provides the screen on the results for
the selected physicochemical calculators for the selected metabolite, tetrachloroethane, as shown
in the screen shot below.
Display up to:
l2ndpen
Total Pro ducts: 6
- View Molecular Information
Molecular Information
mics CC0CI|qC)C
nuns HydrDgc-"inlyiii
Sercr^or makmlc 1.1J
fa-nula C2H2CI*
lupjr 1,1^2-tciTachlanMthm
rrusG I67.M
cxocrMjss IfiS.BSlOSm
43
-------
¦ Calculate PtLysicochemical Properties
Calculate physicacbanical properties for | selected rretafcoiice
Select pnrysicochernica properties to gather for selected metabolite, then click "Calculate
data" below..
~hi
~
ChcfTiAicon
~
EPl Suite
~
TEST
~
OPERA
Seometnc
Mean
0
Measured
Neutral Sped.es Inputs:
|~~|Melclna Point |"Q
-4s.ee
-43. BO
HC
44. &fl
MM
-27.90
GC
-S.B3
-42.65
-43.30
~BQ»ig Point (*Q
141.90
! 40.50
HC
130.BQ
MM
140.50
GC
I47.SB
140.39
14€lSC'
Qwacer Solubility
4.23C+2
l.25e+3
WSKOW
I.B5e*3
WATBRMT
2.73c*3
HC
3JBC-3
MM
7A2C+2
GC
2.96C-3
L37C+3
ZS3C+3
GDvapor Pressure immHgl
4.72D+0
SDfic^O
HC
6.91c*0
MM
Sw13cH0
GC
7.29C-KD
5.40c*O
^3SC*^
|~1 Ionization Constant
TKK1C
none
r~|Hcnry5 Law Constant (atnv
m'/mof]
l.Slc-3
S.Olc-4
l.Sle-3
3A6C-4
EDoaanof/W-accr Partition
Coefficient i.logl
iS4
mop
ZD6VG
zm
AHre
2.T9
2.35
zes
2.39
QorganK Carbon Partition
Coefficient 0qg(L/Hg])
1.98 MCI
2.07 KOW
I.B9
2.03
("jBioconccntratior Factor .'log
(LUgR
1.24 REG
1.29 A-G
136
SM
1.04 HC
1.09
MM
I27GC
1.07
1.22
Qbioaccumutation Fane* (tag
1.29 AG
1.23
pH-Dependent Innate at
pH: 7.C- |
noctancrt/Water Distribution
Coefficient i lo.gl
l~lwacer Solubility {rng/l}
¦ZSSc+3
Available Urjvdlaac
dear data I Calculate data
44
-------
The screen shot above indicates the total number of products that are predicted. If the total
product = 0, then the user is to assume the selected reaction processes do not occur for the parent
chemical of interest.
To get physicochemical data for multiple metabolites, select the option for calculating
physicochemical properties for up to the first, second, or third generation of metabolites, or for
all calculated metabolites from the drop-down menu. Then, select the properties and calculators
to be used and click the Calculate data button. The results for multiple metabolites will not be
presented in the table as they are for a single metabolite. To view the results for multiple
metabolites, download and view the report (as a PDF, CSV, or HTML file) as described below.
Generation of PDF, HTML and CSV Reports
The .pdf, .html and .csv buttons appear on the top right corner of the results page, regardless of
the workflow. Clicking on the .pdf button generates a PDF file that can be viewed in the web
browser or using free PDF software. The HTML file can be viewed using a web browser.
The PDF and HTML reports are multi-page reports showing the calculated physicochemical data
for the parent compound and the selected transformation products. Examples of the PDF and
HTML reports are shown below in the first two screen shots.
PDF Report
45
-------
1
o o
1
1
CI
CI
)H
—
—
Z.U.
t-KBOWIta
-
-
•>
HTML Report
The CSV report is generated in a tabular format as shown below in the screen shot.
A
B
C D E
F
G
1
genKey
routes
smiles iupac formula
mass
exactMass
2
1
ClC(Cl)(Ci; hexachlor C2CI6
236.72
233.8131
3
1.1
Halogenal OC(Cl)(Cl} pentachlo C2HCI5Q
218.28
215.847
4
1.2
Hydrogen
CIC(CI}C{C 1,1,1,2,2-f C2HCI5
202.28
199.8521
5
1.2.1
Hydrogen
ClC=C(Cl)( 1,1,2-trich C2HCI3
131.38
129.9144
6
1.2.2
Hydrogen
CIC(CI)=C( tetrachlor C2CI4
165.82
163.8754
7
1.2.3
Hydrogen
OC(Cl)(Cl) l,l,2,2-te1 C2H2CI40
183.84
181.886
8
1.2.4
Hydrogen
OC(Cl)C(C l,2,2,2-te1 C2H2CI40
183.84
181.886
9
1.2.5
Hydrogen
ClCC{Cl}(C 1,1,1,2-tel C2H2CI4
167. S4
165.8911
10
1.2.6
Hydrogen
CIC(CI)C(C l,lr2,2-te1 C2H2CI4
167.84
165.8911
11
1.3
Vicinal De
CIC(CI)=C( tetrachlor C2CI4
165.82
163.8754
12
1.3.1
Vicinal De
ClC=C(CI)C 1,1,2-trich C2HCI3
131.38
129.9144
CSV Report
46
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