Using the UNIFAC program
************************

COSMO-RS UNIFAC Activity coefficient Vapor pressure Solubility VLE LLE

The UNIFAC program is an implementation of the UNIFAC method, a fast
and accurate liquid-phase activity coefficient model.  One of the main
advantages of the UNIFAC method is that it does not require any ADF
calculations and can estimate thermodynamic properties based only on
SMILES strings representations of every molecule in the system (this
can also be done with COSMO-RS using FastSigma) .  This means that the
UNIFAC method can be applied to liquid systems for which no 3D/surface
charge information is known.  Additionally, UNIFAC is very efficient,
able to generate thermodynamic property estimates in milliseconds.  In
the following sections, we review basic GUI functionality for the
UNIFAC program.


Selecting/inputting compounds
=============================

Molecules can be used with the UNIFAC program in two ways:

**(1)** Simply choosing them from the ADFCRS compound database.

**(2)** Inputting a SMILES string in **Compounds → Add Compound using
FS1 (Fast Sigma) → Add**.  This will generate a .compkf file, which
will appear in the compound database and can be used with UNIFAC
calculations.

Caution:

  In the current version of the GUI, you can only add a compound by
  SMILES string if the method **COSMO-RS** or **COSMO-SAC** is
  selected.  It will not work if **UNIFAC** is selected.

To input a molecule as a SMILES string, simply follow the instructions
above, typing the SMILES string in the field.  As an example, we enter
the SMILES string, **C1CCCCC1O**, of cyclohexanol:

[image]

This will prompt you to save your compound as a .compkf file.  After
saving it, it should appear in the database.


Inputting property values
=========================

For some types of UNIFAC calculations, physical property data will be
required.  For most applications, all of the required physical
property data can be input from the compounds menu: **Compounds → List
of Added Compounds**.  Property input fields are given in the right
panel.  As an example, we click "estimate" in the vapor pressure
equation section to estimate the VPM1 vapor pressure coefficients for
cyclohexanol :

[image]

Note that other properties (enthalpy of fusion, melting point, etc.)
can be input or estimated with a Property Prediction Method.


Calculations with the UNIFAC program
====================================

To begin, first navigate to the UNIFAC method:

   Start AMScrs (if not already open)
   Select **Method → UNIFAC**
 [image]

All of the available properties for UNIFAC are listed under
**Properties →**:

[image]

Pure Compound Properties provides estimated physical properties for a
compound, but the rest require a UNIFAC calculation.  The rest are
summarized in the following subsections.


Vapor Pressure Mixture
----------------------

   **Properties → Vapor Pressure Mixture**

For this calculation, we also select water from the ADFCRS database.
We click "estimate" next to Vapor pressure equation for Water in
**Compounds → List of Added Compounds**.  Also, make sure the vapor
pressure parameters are already estimated for cyclohexanol (this was
done in a previous section). Next, we navigate to the **Properties →
Vapor Pressure Mixture** window.  We choose a two component mixture of
0.8:0.2 cyclohexanol:water and change the temperature range to 250-350
K.  After hitting "Run", we obtain the following:

[image]


Activity Coefficients
---------------------

   **Properties → Activity Coefficients**

Next, we demonstrate the activity coefficient calculation module.  In
this example calculation, we calculate the activities of a 0.9:0.1
Methanol/Water system (both compounds were selected from the ADFCRS
database).  Additionally, we calculate the activity coefficient of
aniline at infinite dilution in this system:

[image]


Partition Coefficients (LogP)
-----------------------------

   **Properties → Partition Coefficients (LogP)**

In this example, we calculate the logP of Ibuprofen, Thymol, and
Xylitol in the standard Octanol/Water system.

[image]

Caution:

  Only the presets work in the current implementation.  User-defined
  solvent systems will not work.


Solubility in Pure Solvents
---------------------------

   **Properties → Solubility in Pure Solvents**

In this example, we calculate the solubility of Ibuprofen in a few
different solvents: Methanol, Water, and Cyclohexanol (from our input
SMILES string).  We also want to consider the solubility over the
temperature range 250-298.15 K.  Because Ibuprofen is a solid at these
temperatures, we require its Enthalpy of Fusion and Melting Point.  We
can either enter experimental values or estimate the values in the
**Compounds → List of Added Compounds** menu.  Even though these
properties are known experimentally, we will opt for convenience by
clicking the "estimate" in Enthalpy of Fusion and Melting Point as
shown below:

[image]

Now, we can navigate to **Properties → Solubility in Pure Solvents**
and input the following:

[image]


Solubility in Mixture
---------------------

   **Properties → Solubility in Mixture**

Solubility in Mixture is very similar to Solubility in Pure Solvents.
In this case, we specify a mixture of cyclohexanol and water and
estimate the solubilities of Ibuprofen and Cortisone in that mixture
from 250 K to 320 K.  Since Cortisone is also a solid over this
temperature range, we first have to estimate its melting temperature
and enthalpy of fusion from the **Compounds → List of Added
Compounds** menu.  The calculation looks like the following:

[image]


Binary Mixture VLE/LLE
----------------------

   **Properties → Binary Mixture VLE/LLE**

To demonstrate the Binary Mixture module, we again use our
cyclohexanol/water system because we've already estimated the VPM1
coefficients.  If just beginning this tutorial at this step, ensure
that both compounds have estimated vapor pressure equations.  If vapor
pressure information is not provided, the vapor pressure will be set
to 0 and VLE data will not be meaningful.  After running the
calculation, we adjust the default graph display to view the excess
energies.  This can be done with **Graph → Y Axes → excess energies**.
The result is the following:

[image]


Ternary Mixture VLE/LLE
-----------------------

   **Properties → Ternary Mixture VLE/LLE**

Next, we add a ethoxyethane (diethyl ether) to our cyclohexanol/water
system to investigate the behavior of the ternary mixture.  Make sure
to estimate the VPM1 parameters for ethoxyethane from the **Compounds
→ List of Added Compounds** menu.  Additionally, we change the number
of mixtures to 50.

After running the job, we change the default graph display to a
ternary plot with **Graph → Triangle** \boldsymbol \Delta.  Also, the
background color has been changed to show the activity coefficient of
compound 2 (water) at the different mole fractions.  This was done
with **Graph → Z Colormap → gamma2**.  This results in the following:

[image]


Common issues
=============

The most frequently encountered issue with the UNIFAC program is
termination due to lack of binary interaction parameters.  Unlike
COSMO-RS/-SAC, UNIFAC requires binary interaction parameters for every
pair of molecular substructures -- called *groups* -- in the mixture.
There are many cases where these binary interaction parameters do not
exist or are not publicly known.  For molecular systems with even one
missing interaction parameter, the UNIFAC model cannot provide an
estimate. The group coefficients and interaction parameters currently
used are source from from The Dortmund Data Bank UNIFAC site.


COSMO-UNIFAC model
==================

For systems where UNIFAC parameters are missing, users can opt for the
COSMO-UNIFAC model as described in Ref. [1]. This model employs
infinite dilution activity coefficients predicted by the COSMO-SAC
model to estimate the missing UNIFAC parameters, providing a reliable
alternative for systems where UNIFAC parameters are unavailable.

To use this model, simply switch from UNIFAC to COSMO-UNIFAC_Lei under
the method/parameters settings.

[1] Zhu, R.; Taheri, M.; Zhang, J.; Lei, Z. *Extension of the COSMO-
    UNIFAC Thermodynamic Model.* Ind. Eng. Chem. Res. 2020, 59 (4),
    1693–1701.
