Teaching with Schrödinger

Updated: 1-23-22

Nucleophiles & Electrophiles
Created with: Release 2021-3
Prerequisites: working knowledge of Maestro
Files Supplied: Chemical_bonding_worksheet
Categories:
organic chemistry

About this Lesson
In this lesson plan, students will examine the behavior of nucleophiles andelectrophiles. Students will learn about inductive effects and how to identify
nucleophilic and electrophilic centers in a molecule. This will help with predicting where
electron density can be found and where it is likely to flow during a reaction.
Using Maestro, students will create a map of electrostatic potential (ESP) of various
nucleophiles and electrophiles with Jaguar and examine the electrostatic potential on
the molecular surface. These renderings will help with visualizing sites of high and low
electron density.

Learning Objectives
Differentiate between nucleophilic and electrophilic centers● Identify electron-rich and electron-poor regions by mapping electrostatic
potential surfaces onto molecules●

1
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Standards:●

ACS Guidelines○●

ETS Chemistry GRE○●

Properties of Molecules (Conceptual Topics)
Organic Chemistry – Structure, Bonding, and Nomenclature (3.A)

AAMC MCAT○Nature of molecules and intermolecular interactions (5B)

Assessments
The following types of formative assessments are embedded in this lesson:●●

Assessment of student understanding through discussion of warm-up questions andfilling in any knowledge gaps of inductive effects
Visual assessment of student-generated electrostatic potential surfaces of nucleophilicand electrophilic centers

Warm-Up Questions: To be done on their own or at the beginning of class
Watch the Khan Academy videos on nucleophilicity and basicity.
1) Identify the nucleophilic center of each molecule.

2) Identify the electrophilic center of each molecule.

2
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Lesson Outline
1.
2.
3.
4.
5.
6.
7.

1.

What you will need for this lesson - p. 3
Polar Bonds, Induction, and Electronegativity - p. 5
Nucleophiles - p. 7
Electrophiles - p. 20
Individual Exercise - p. 33
Summary, Additional Resources, and References - p. 34
Glossary of Terms - p. 34

What you will need for this lesson
1. Go to the ‘Data’ folder and open yourClass Folder found on the virtual
cluster’s desktop.
2. Right-click on the folder called“Nucleophiles” and copy folder to
Desktop● Here, you will find the lesson
plan, worksheet, and any
additional resources
3. Open Maestro
a. See Starting Maestro if you
need help

Figure 1-1. Open Maestro.

3
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

4. Go to File > Change Working
Directory
5. Find your “Nucleophiles” folder thatyou duplicated to your Desktop, andclick Choose

Figure 1-2. Change Working Directory option.

6. Next, go to File > Save Project As
7. Type “Nucleophiles_tutorial” andclick Savea. The project will be titled
Nucleophiles_tutorial.prj

Figure 1-3. Save Project panel.

Figure 1-4. Choose the best mouse option foryour set up.

8. Finally, check your Mouse Actions
a. PC : Edit > Customize Mouse
Actionsb. Mac : Workspace >Customize Mouse Actions
9. Make sure you have the best option
chosen for your set up. This lesson
was written with a three-button mousewith a scroll wheel. If you do not havea mouse, choose Trackpad.

4
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

2.

Polar Bonds, Induction, and Electronegativity

Bond polarity is a measure of how equally or unequally the electrons in any
covalent bond are shared. A nonpolar covalent bond is one in which the electrons areshared equally, like in Cl2, N2, or H2. In the case of Cl2, each atom starts off with sevenvalence electrons, and each Cl shares one electron with each other forming one
covalent bond.

Figure 2-1. Nonpolar covalent bond of Cl2
The total number of electrons around each individual atom consists of six nonbonding
electrons and two shared, bonding electrons for eight total electrons. This matches thenumber of valence electrons in the closest noble gas argon (Ar). Since the bonding
atoms are identical, Cl2 contains a nonpolar covalent bond.
In a polar covalent bond, there is an unequal distribution of electrons which ischaracterized by a partial positive charge on one atom and a partial negative change on
the other. The atom that attracts the electrons more strongly acquires the partial
negative charge and vice versa. For example, the electrons in the H–Cl bond of ahydrogen chloride atom spend more time near the more electronegative chlorine atom
than near the hydrogen atom. Therefore, the chlorine atom carries a partial negative
charge while the hydrogen atom has a partial positive charge. We can represent thischarge distribution as:

Figure 2-2. Polar covalent bond of H–Cl
The δ+ (delta plus) and δ– (delta minus) symbolize the partial positive and negative
charges, respectively. In a polar bond, these numbers are less than a full charge of theions.
Electronegativity is the ability of an atom in a molecule to attract electrons toitself and is used to estimate whether a given bond is nonpolar covalent, polar covalent,or ionic. The greater an atom’s electronegativity, the greater its ability to attract electrons
to itself. American chemist Linus Pauling developed an electronegativity scale, which isbased on thermochemical data shown below.

5
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Figure 2-3. Linus Pauling’s Electronegativity Scale
The absolute value of the difference in electronegativity (ΔEN) of two bonded atoms
provides a rough approximation of the polarity to be expected in the bond and, thus, thebond type. Note that electronegativity values have no units. When the difference is verysmall or zero, the bond is nonpolar covalent. When the difference is between 0.4 and
1.8, the bond is polar covalent. When the difference is above 1.8, the bond is ionic. A
table summarizing electronegativity differences and bond types is shown below.
Bond TypeElectronegativity Difference

Nonpolar covalent< 0.4

Polar covalent

0.4 – 1.8

Ionic

> 1.8

Table 2-1. Summary of bond types based on electronegativity differences
Induction (or inductive effect) is due to the difference in electronegativity ofatoms bonded together. A bond between two atoms is polarized if there is a difference
between their electronegativities. This polarization of the bond causes the appearanceof partial charges (δ+ and δ–), which may have effects on close-by neighboring bonds.
Some effects may be electron withdrawal which often occurs on atoms that are more
electronegative than carbon (O, N, F, etc.), or electron repelling which often occurs on
6
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

atoms that are less electronegative than carbon (Mg, Al, etc.). We will visualize
inductive effects in various nucleophiles and electrophiles using calculated electrostatic
potential maps later in this lesson.

3.

Nucleophiles

A nucleophile contains an electron-rich center and comes from the Greek
meaning “nucleus lover”. Nucleophiles provide the electrons to make a new bond in a
substitution reaction (either SN1 or SN2). A nucleophilic center is characterized by its
ability to react with a positive charge or partial positive charge by donating a pair ofelectrons. There are three different kinds of electron-rich regions:
1) nonbonding electrons (present on oxygen, nitrogen, and negatively charged

carbon atoms called carbanions) – Atoms that possess nonbonding lone pairs ofelectrons are nucleophilic. Note that lone pairs of electrons may not always be
drawn in molecular structures so be aware of the octet rule and feel free to draw
them in if they are not shown.
2) a carbon atom bonded to a metal, such as a Grignard/organomagnesium ororganolithium – A carbon atom bonded to a metal has a strong negative
character which can be shown through writing a resonance structure. The
carbanion is considered to be a strong nucleophile.
3) π bonds – A π bond is also a region of high electron density. Since π bonds are

not as strong as σ bonds, π electrons are more available to react in a reaction
because π bonds can break more easily. Molecules containing π bonds are
considered to be weak nucleophiles and can react with strong acids orelectrophiles.

7
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Nucleophilicity is a kinetic property measured by the rate at which a nucleophilecauses a substitution reaction to occur. Certain reactions are better with strong
nucleophiles while others are better with weak nucleophiles. Some factors that
contribute to nucleophilicity include:
1) Charge – As electron density on an atom increases, so does nucleophilicity

2) Basicity – The stronger the base, the greater the nucleophilicity

3) Electronegativity – For atoms in the same row of the periodic table, as

electronegativity increases, nucleophilicity decreases

4) Solvation effect – Depends on whether the reaction is in polar protic or polar

aprotic solvent. In polar protic solvents, nucleophilicity increases going down the
periodic table. In polar aprotic solvents, nucleophilicity increases going up the
periodic table5) Steric hindrance (or bulkiness) – The less bulky, the better the nucleophile since

it is easier for the nucleophile to backside attack

8
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Example #1: Rank the following compounds in order of increasing nucleophilicity.

9
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Computational Exercise #1: Generating Electrostatic Potential (ESP)
Maps on the Molecular Surface
Now we will calculate the electrostatic potential surfaces of ethanol and ethoxide
to visually identify which nucleophile is strong and which is weak. ESP maps will show
the electron-density distribution on the surface of the molecules. This exercise involves
three parts:
1) Build the molecules and minimize their geometries
2) Generate surfaces of the molecules
3) Map the electrostatic potentials to the molecular surfaces

Part 1. Build the molecules and minimize
their geometries
Before generating any surfaces, build andminimize the structures for ethanol andethoxide4) Go to Edit > 2D Sketcher

Figure 3-1. Open 2D Sketcher.

10
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

5) Draw ethanola) Go to the selection bar on theleftb) Choose the single bond buttonc) Click and drag in theworkspace to form ethaned) Click and drag again from oneof the carbon atoms to form
propane (linear 3-carbon
chain)e) Click “O” in the selection bar
and click the end of the single
bond to change a carbon to
OH at the end6) Click on Save as New and for Input
Entry Title write Ethanol. Click OK.
Figure 3-2. Drawing ethanol.

Figure 3-3. Saving Ethanol.

11
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Figure 3-4. Drawing Ethoxide.

7) Draw ethoxidea) Go to the selection bar on theleftb) Choose the single bond buttonc) Click and drag in theworkspace to form ethaned) Click and drag again from oneof the carbon atoms to form
propane (linear 3-carbon
chain)e) Click “O” in the selection bar
and click the end of the single
bond to change a carbon to
OH at the endf) Click the lightning bolt
Decrease Charge button thenclick the Oxygen atom in yourmolecule. This removes the Hfrom OH and adds a negative
charge to O.
8) Click on Save as New and for Input
Entry Title write Ethoxide. Click OK.

Figure 3-5. Saving Ethoxide.

12
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Viewing multiple molecules at the same time
can be important for comparing andcontrasting them. We will show ethanol andethoxide side by side so we can easily see
how they differ.

Figure 3-6. Including both molecules.

9) Simultaneously include (control +click or command + click) all
molecules

10) Show workspace configuration panel
by clicking the Plus symbol at thebottom right corner
11) Click Workspace Layout > Tile

Figure 3-7. Tiling both molecules.

13
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Figure 3-8. Selecting both entries.

12) Simultaneously select (control + click
or command + click) all molecules13) Change their representations toball-and-stick by clicking on the Stylemenu and choosing Applyball-and-stick representation
14) Include atom labels if you’d like byclicking Apply Labels > Custom
Label

Figure 3-9. Applying ball-and-stick style to all
entries.
15) To center all the molecules within theirrespective areas, click Fit view to all
visible objects
Figure 3-10. Centering the views of all three
entries.

14
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

16) Select all three molecules in theworkspace (there are many
approaches to do so: Main Menu,
Select > All; Toolbar, Quick Select, All,
Shift + Click + Drag and more)17) In the Build dropdown from thetoolbar (3D Builder panel), selectMinimize selected atoms○ The molecule is minimized,
and the parameters adjustslightly

Figure 3-11. Performing force field
minimization on all entries
Part 2. Generate surfaces for themolecules
Figure 3-12. Open the Jaguar - Single Point
Energy Panel.

18) Select all three molecules – we will berunning the next calculations inparallel19) Open the Jaguar - Single Point
Energy panel from the Task buttona) Click Browse > Jaguar >Single Point Energyb) Or, type Single Point Energy
in the search bar

15
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

20) In the Properties tab, select the row
for Surfaces and click the check boxa) The Surfaces controls are
displayed21) In the Surfaces section, selectElectrostatic potential and Electron
densities, and ensure that no othersurface types are selected22) Ensure that Density only is selectedunder Electron densities
Figure 3-13. Choosing the surface controls
under the Properties tab.
23) Check the box for Atomic
electrostatic potential charges(ESP) in the Properties table

Figure 3-14. Choosing atomic electrostatic
potential charges under the Properties tab.

Figure 3-15. Running the ESP jobs in parallel.

24) Name the job ESP
25) Adjust the settings by clicking the gearicon26) Choose localhost (4) as the Job Host
27) Click Runa) When the jobs finish, thestructures are imported andthe electron density surfaces
may be displayedb) The incorporated jobs will beshown in a separate Entry
Group in the Entry List
16

The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Figure 3-16. Adjusting the job settings.
Part 3. Map the electrostatic potential tothe molecular surfaces28) Click the S button in the Entry List for
Ethanol and choose Managea) The Manage Surfaces panel
opens

Figure 3-17. Clicking the S button in the Entry
List and choosing Manage.
29) Click the In column for the electron
density surface to include it in theWorkspace30) Click Display Options
Figure 3-18. Choosing settings in the Manage

17
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Surfaces panel.

a) The Surface Display Options
panel opens
31) For Color scheme, select Mappedfrom volume32) Select Ethanol_loner2_potentialfrom the volume data list
33) From the Color ramp option menu,
choose Rainbow
34) Click OK35) Repeat steps 25-31 for Ethoxide.

Figure 3-19. Choosing settings in the Surface
Display Options panel

18
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

36) Once you have displayed bothelectrostatic potential surfaces, tile themolecules so we can compare thema) Click Workspace Layout >Tile37) Feel free to play around with themand notice any similarities ordifferences between each molecule

Figure 3-20. Tile both electrostatic potential
surfaces.

When analyzing electrostatic potential surfaces, red represents regions of high electron
density while purple represents regions of low electron density. See the range shown
below:Take a screenshot of the two electrostatic potential maps of ethanol and ethoxide andput it into your worksheet. In a few sentences, analyze any differences you see between
the two surfaces. Determine which regions of each nucleophile dictate its strength, orlack thereof, towards attack of an electrophile.

19
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Both ethanol and ethoxide contain oxygen atoms with lone pairs, so both
molecules can act as nucleophiles. The ethoxide ion contains a negative charge on theoxygen atom making it a stronger nucleophile than the neutral ethanol molecule. This isindicative in their electrostatic potential maps – the red, more electron dense region islarger in ethoxide whereas the red region in ethanol is more localized to only the oxygen
atom. Ethanol is a weak nucleophile because it is overall neutral whereas ethoxide is astrong nucleophile because it is negatively charged.
The strength of ethoxide is affected by polarizability. Polarizability is the abilityof an atom to distribute its electron density unevenly in response to external influences.
For example, HS– is a particularly strong nucleophile because sulfur is a large atom withmany electrons distant from the nucleus. Sulfur’s polarizability causes its electron
density to be unevenly distributed as it attacks an electrophile.
This example represents a standalone comparison of these two nucleophiles; it isimportant to note that the solvent in which these two nucleophiles may react in may
change its nucleophilicity towards a given substrate.

4.

Electrophiles

An electrophile is an “electron loving” species that is typically either positively
charged or has a partial positive charge (δ+). An electrophilic center is anelectron-deficient atom that is capable of accepting a pair of electrons, similar to that ofa Lewis acid. Two examples of electrophiles are:1) An electrophilic carbon atom from inductive effects of a halide2) A carbocation which is a positively charged carbon atom – a carbocation has an

empty p orbital that functions as a site that can accept a pair of electrons.

Electrophiles may have electron-withdrawing groups which is a group containing
electronegative elements pulling the electron density towards them. Furthermore,
electrophiles may also have polarizable π-bonds such as C=O or C=N bonds wherepartial charges can be drawn in.
20
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Example #2: Predict where the nucleophilic and electrophilic centers are in thefollowing molecule (E)-hept-5-en-2-one. Draw in any partial charges if applicable.

Computational Exercise #2: Optimizing the Geometry and Generating
an Electrostatic Potential (ESP) Map on the Molecular Surface on(E)-hept-5-en-2-one
Now we will optimize the geometry of (E)-hept-5-en-2-one and calculate theelectrostatic potential surfaces to visually show the electron-density distribution on thesurface of the molecule. This exercise involves four parts:
1) Build the molecule and minimize its geometry2) Optimize the geometry using quantum mechanical DFT3) Generate surface of the molecule4) Map the electrostatic potentials to the molecular surfaces

21
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Part 1. Build (E)-hept-5-en-2-one using 2D
Sketcher
Before optimizing any molecular geometry,
you will need a starting molecule in yourworkspace. Let’s draw the structure of(E)-hept-5-en-2-one using the 2D sketcher.
1. Go to Edit > 2D Sketcher

Figure 4-1. Open 2D Sketcher.

Figure 4-2. Draw (E)-hept-5-en-2-one

2. Draw the structure of(E)-hept-5-en-2-one. You do not needto draw in any lone pair of electrons;
only show the bonds.
○ Go to the selection bar on theleft○ Choose the single bond button○ Click and drag in yourworkspace to form ethane○ Continue to click and drag until
you form heptane (7-carbon
linear chain)○ Click and drag at the C2
position from the right to draw
a methyl group○ Click the center of this bond toform an alkene○ Click the Oxygen atom to add
an O to the end of the alkene
you just made; this makes acarbonyl22
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

○

Choose the single bond button
again and click the center of
the C5–C6 bond to form a
double bondNote: You could also use O on your keyboard
for atom assignments.
The 2D sketcher functions like many standard
2D molecular drawing tools. For a complete
overview of using the sketcher panel, see the2D Sketcher Panel documentation.
3. Click on Save as New
4. For Input Entry Title, write
E-hept-5-en-2-one. Click OK.

Figure 4-3. Saving (E)-hept-5-en-2-one
6. Close the 2D Sketcher panel○ The (E)-hept-5-en-2-one
molecule is selected in theentry list and included in theworkspace
7. Change the representation toball-and-stick by clicking on the Style

23
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Figure 4-4. Viewing and styling(E)-hept-5-en-2-one

menu and choosing Applyball-and-stick representation
8. Change the color of the atoms byclicking on the Style > Color Atoms >Element + Custom Ligand

9. To display atom labels, click Style >Apply Labels then click the drop
down arrow on the right side
10. Click Edit Custom Labeling
11. Checkbox Element and press OK
12. Go back to Style > Apply Labels >Custom Label and now each atom inyour workspace should be labeled
Note: You can toggle the atom labels on andoff by clicking Annotations label button in theWorkspace toggle on the bottom right corner

Figure 4-5. Labeling atoms.

Figure 4-6. Toggling labels on.

Figure 4-7. Toggling labels off.

24
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Part 2. Force Field Minimization
We can improve upon this starting structureby using a force field minimization. The
molecule will still not be optimized byquantum mechanics (QM), but it will improve
the starting geometry.

Figure 4-8. Force field minimization.

13. Select all atoms in the workspace(there are many approaches to do so:
Main Menu, Select > All; Toolbar,
Quick Select, All, Shift + Click + Dragand more)
14. In the Build dropdown from thetoolbar (3D Builder panel), selectMinimize selected atoms○ The molecule is minimized,
and the parameters adjustslightly
Note: Force fields are usually good at
generating structures of molecules with
common functional groups and elements.
When it comes to more exotic atomic
arrangements and less frequent elements(such as transition metals) or simply large
molecules, force fields can yield structureswith inaccurate or even unphysicalgeometries, and in those cases, quantum
mechanical geometry optimizations become
absolutely indispensable.

Part 3. Optimize the Geometry using
Quantum Mechanic DFT
Now let’s optimize the molecule at thequantum mechanical level.

25
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Figure 4-9. Opening the Jaguar Optimization
panel.

Figure 4-10. Setting the Jaguar Optimization
panel to optimization.

15. With the (E)-hept-5-en-2-one entry
selected and included, go to Tasks >Optimization using Jaguar○ Type optimization in the Tasks
search bar○ The Jaguar Optimization panel
opens
16. Use structures from Project Table (1selected entry)
Note: We are optimizing one molecule,(E)-hept-5-en-2-one. By selecting many
molecules in the entry list, we can optimize as
many molecules as we would likeconcurrently with the same QM settings.

Various settings can be altered depending on
the specific use case. We will only adjust the
Input tab for this example.

Figure 4-11. Setting the QM parameters for
optimization.

17. For Theory, select B3LYP-D3
18. For Basis set, select 6-31G**

A few additional comments about preparing for an optimization calculation:●

If you hover the mouse over the basis set in the table, you can see the number ofbasis functions associated with the basis set. This is useful to know since the quality ofthe basis set usually improves as the number of functions increases, noting again the
trade-off between quality and computational expense●

Always make sure the charge and the spin multiplicity are correct (in this case,(E)-hept-5-en-2-one is a neutral, singlet, so charge = 0 and spin multiplicity = 1).
Multiplicity is defined as 2S + 1, where S is the total orbital spin of the molecule. For
instance, a system with one unpaired electron is a doublet (multiplicity = 2), since thetotal orbital spin S = ½.

26
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

●

Use the Atom-Level Settings button to define per-atom basis sets●

Constraints can be defined on the Optimization tab●

Properties, such as atomic charges, vibrational frequencies, surfaces and more can berequested on the Properties tab●

Solvent can be defined via several implicit solvation models on the Solvation tab. Notethat this example is a gas-phase geometry optimization●

Read more about geometry optimization with Jaguar here
19. Change the Job name toE-hept-5-en-2-one_opt_B3LYP-D3_6-31GSS○ Usually we incorporate stars(*) and pluses (+) into filenames with S and P,
respectively
20. Adjust the job settings ()○ This job requires a CPU hostand should complete in under
5 minutes
21. Click Run

Figure 4-12. Naming and running the job.

Note: It is advised to also add in a Vibrationalfrequencies calculation (from the Propertiestab). This involves a bit more computational
expense, but is a useful way to be sure thatyour output is a minimum (as opposed to a
maximum) on the Potential Energy Surface(PES). For more detail, see the Locating
Transition States tutorial.
When a job is submitted to the queue, you
can check its status by clicking the Jobs
button in the upper right-hand corner●

If the job is in the queue, it will say‘Waiting’27
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Figure 4-13. Status when a job is in thequeue.

●

If the job is in progress, it will say‘Running’

When the job finishes, a banner will appear
indicating that the result has been
incorporated. At this time, the molecule withthe optimized geometry is now shown in theworkspace

Figure 4-14. Status when a job is running.

22. A new entry group is added to theentry list titled
E-hept-5-en-2-one_opt_B3LYP-D3_631GSS.011 (1). This is your optimized
structure.
○

Figure 4-15. The output molecule of PCl3.

Your structure may look a bit
different because you may
have built a different
conformer. This is okay andyou can still proceed to thenext step as it will not change
your ESP results.

Part 3. Generate the ESP surface for themolecule
Figure 4-16. Open the Jaguar - Single Point
Energy Panel.

23. Select the optimized molecule
24. Open the Jaguar - Single Point
Energy panel from the Task button○ Click Browse > Jaguar >Single Point Energy○ Or, type Single Point Energy
in the search bar

28
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

25. In the Properties tab, select the row
for Surfaces and click the check box○ The Surfaces controls are
displayed
26. In the Surfaces section, selectElectrostatic potential and Electron
densities, and ensure that no othersurface types are selected
27. Ensure that Density only is selectedunder Electron densities
Figure 4-17. Choosing the surface controls
under the Properties tab.
28. Check the box for Atomic
electrostatic potential charges(ESP) in the Properties table

Figure 4-18. Choosing atomic electrostatic
potential charges under the Properties tab.

Figure 4-19. Running the ESP job.

29. Name the job
ESP_E-hept-5-en-2-one_B3LYP-D3_6-31Gss
30. Adjust the settings by clicking the gearicon
31. Choose localhost (4) as the Job Host
32. Click Run○ When the jobs finish, thestructures are imported andthe electron density surfaces
may be displayed

29
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

○

The incorporated jobs will beshown in a separate Entry
Group in the Entry List

Figure 4-20. Adjusting the job settings.
Part 4. Map the electrostatic potential tothe molecular surfaces
33. Click the S button in the Entry List for
Ethanol and choose Manage○ The Manage Surfaces panel
opens

Figure 4-21. Clicking the S button in the Entry
List and choosing Manage.

Figure 4-22. Choosing settings in the Manage
Surfaces panel.

34. Click the In column for the electron
density surface to include it in theWorkspace
35. Click Display Options○ The Surface Display Options
panel opens

30
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

36. For Color scheme, select Mappedfrom volume
37. SelectESP_E-hept-5-en-2-one_B3LYP-D3_
6-31Gss_potential from the volumedata list
38. From the Color ramp option menu,
choose Rainbow
39. Click OK

31
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Figure 4-23. Choosing settings in the Surface
Display Options panel

Take a screenshot of your electrostatic potential map and analyze the nucleophilic andelectrophilic regions of (E)-hept-5-en-2-one.

32
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

5.

Individual Exercise

All three molecules below contain carbon atoms but some act as a nucleophile whilesome act as an electrophile.

For each of the molecules:a) Build the molecules in Maestro using the 2D sketcher and minimize thestructures.
b) Optimize their geometries using Jaguar. Take screenshots of your optimized
structures with a ball-and-stick representation (from the Style toolbar).
● Theory: B3LYP-D3, Basis set: 6-31gss● Use local host to run the jobsc) Run single point calculations using Jaguar to generate electrostatic potential
maps. Take screenshots of each ESP map.
● Theory: B3LYP-D3, Basis set: 6-31gss● Use local host to run the jobsd) Determine whether the carbon atoms are nucleophilic and electrophilic centers.

33
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

6.

Summary, Additional Resources, and References

In this lesson, you learned about nucleophiles and electrophiles. A nucleophile is areactant that provides a pair of electrons to form a new covalent bond whereas anelectrophile is a reactant that accepts a pair of electrons. You learned about inductive
effects and how to identify nucleophilic and electrophilic centers in a molecule.
Understanding how electrons flow from electron-rich regions to electron-poor regions
is essential in learning organic chemical reactions.
Using Maestro, a simple geometry optimization using Jaguar can be performed to show
a molecule’s structure. Electrostatic potential surfaces can also be generated tovisualize electron-poor and electron-rich regions in both nucleophiles and electrophiles.
For further learning:
●
●
●
●
●

7.

Exploring potential energy surface for chemical reactions: An overview of some
practical methods. DOI:10.1002/jcc.10231
Introduction to Computational Chemistry, 3rd Edition
Essentials of Computational Chemistry: Theories and Models, 2nd Edition
Molecular Modelling: Principles and Applications, 2nd Edition
See the Jaguar help documentation

Glossary of Terms

Entry List - a simplified view of the Project Table that allows you to perform basic
operations such as selection and inclusion
Included - the entry is represented in the Workspace, the circle in the In column is blue
Project Table - displays the contents of a project and is also an interface for performing
operations on selected entries, viewing properties, and organizing structures and data
Recent actions - This is a list of your recent actions, which you can use to reopen apanel, displayed below the Browse row. (Right-click to delete.)
Scratch Project - a temporary project in which work is not saved. Closing a scratch
project removes all current work and begins a new scratch project34
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.

Selected - (1) the atoms are chosen in the Workspace. These atoms are referred to as"the selection" or "the atom selection". Workspace operations are performed on theselected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row
for the entry is highlighted. Project operations are performed on all selected entries
Working Directory - the location that files are saved
Workspace - the 3D display area in the center of the main window, where molecular
structures are displayed

35
The recipient shall not use the Schrödinger software, materials and information other than for the purposes for which they were distributed. Schrödinger owns the software and all materials, and retains all related
intellectual property rights. Schrödinger will retain all intellectual property rights relating to any suggestions, ideas, enhancement requests, feedback, recommendations or other information provided by therecipient or any third party. The recipient shall not use Schrödinger’s names or marks without Schrödinger’s prior written consent. THE SOFTWARE AND MATERIALS ARE PROVIDED "AS IS" WITHOUTWARRANTY OF ANY KIND. TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL SCHRÖDINGER OR ITS AFFILIATES OR LICENSORS BE LIABLE FOR ANY SPECIAL,INCIDENTAL, INDIRECT, CONSEQUENTIAL, PUNITIVE OR EXEMPLARY DAMAGES.