ChemPad

Organic Chemistry

The study of carbon-containing compounds and their properties.

A critical and difficult college course for aspiring chemists and doctors.

Visualizing 3D Molecules

The ability to understand the 3D nature of molecule and their 2D representations is key to mastering chemistry. The 3D form of a molecule determines its

properties.

Visualizing 3D Molecules

Project Goals

To create a pedagogically-oriented Tablet PC application which converts hand drawn molecules into 3D models.

For the tool to be stable and usable in Chem 35 in Spring 2005. Partnered with Professor Matthew Zimmt

from Chemistry.

Existing Tools Cambridgesoft ChemDraw.

Doesn’t generate 3D models. Doesn’t use handwriting.

Professional molecule modeling software. Only generates 3D. Too complicated for beginning chemists.

ACD Labs ChemSketch Doesn’t use handwriting. Lousy input method for many basic organic molecules.

Physical “Ball and Stick” models. No 2D version. Very slow work. Easy to spill.

Fluid Inking. Recognizes a large number of handwritten symbols and gestures. Doesn’t know chemistry at all.

Using ChemPad

Demo

Stereochemistry

Some molecular formulas can represent multiple molecules with different 3D structures.

Stereochemistry

Demo

Stage 1: Proof of Concept Model and Design Test Bed.

June-December 2004: 3D scenes built from spheres and

cylinders in DirectX. Inking recognition through XP

recognizers. Unrecognized characters assumed to be bonds.

Molecular Interpreting oblivious to positioning cues in drawing.

No pedagogical tools.

Stage 2: Preparing for Release.

January-February 2005: Refitting of user interface.

DirectX replaced with JMol. SDK Ink control replaced with Fluid Inking.

Rethinking of Interpretation algorithm. Addition of stereochemistry. IRB protocol approval for user study. Version 1.0 code freeze.

Stage 3: Release.

March 2005: Version 1.1 Code Freeze. Used in Organic Chemistry lecture twice. Pilot study week.

12 early adopter students participated. Post quiz deployment.

55 personal invitations. 16 users yesterday afternoon.

Problems Solved: 2D to 3D Mapping. Overview: Place each atom one at a time in

3-space. Find the atom with the highest p-value.

P-value determined by number of stereochemistry indicators available to the atom.

Position this atom at the origin. Use two neighbors to define the XY plane.

Connect atoms along the main carbon chain in the XY plane.

Connect atoms that are off the carbon chain. Connect implicit hydrogen atoms.

Problems Solved: 2D to 3D Mapping.

For each atom, use its atomic number, bond orders, and neighboring bond orders to find the correct 3D template. Tetrahedral Trigonal-Planar Linear Terminal

Problems Solved: 2D to 3D Mapping.

Rotate the template so that its primary connection faces the ‘parent’ atom. Rotate the initial atom to match slope

with the drawing. Use a cross product to determine an axis

perpendicular to both connections. Use a dot product to determine the angle

around that axis.

Problems Solved: 2D to 3D Mapping.

Place the atom at a distance based on the atoms involved and the order of the bond.

When deciding the parent template connection to use, take advantage of cues in the drawing. Wedge and dash notation. Turn directions of the atoms and bonds. Minimize energy conformation for implicit atoms. The parent template may need to be rotated.

Problems Solved: CIP Chemists describe CIP in vague terms.

Higher atomic number takes precedence over lower. When two atoms directly attached to the stereogenic

center are identical, compare the atoms attached to these two on the basis of their atomic numbers. Work outward from the point of attachment and evaluate substituent atoms one by one. Precedence is determined at the first point of difference.

The difference is determined by the substituent of the highest atomic number and is not additive if there is more than one substituent.

Where there is a double or triple bond, both atoms are considered to be duplicated or triplicated.

Problems Solved: CIP Recursively generate a CIP ‘score’

string for each constituent. Base case is a terminal atom. Return the

atomic number expressed as a 3 digit string.

For a non-terminal atom, generate two lists. First is a sorted list of the neighboring

atomic values. Second is a sorted list of the nested scores

of the constituents.

Problems Solved: CIP

Perform an alphabetical string comparison of the scores. Alphabetical ordering finds point of first

difference. String lengths may vary greatly in

length.

Problems Solved: R/S Stereochemistry?

Given a CIP ordering, rotate the lowest priority onto the positive Z axis.

Project the other constituents onto the XY plane.

Note the turn direction from 1 to 2 to 3. Right is R Left is S

Things We Tried

“Rotate” 2D image to match 3D rotation. Chemists didn’t like it.

Multi-stroke symbols using a greedy algorithm. Was prone to errors. Carbon chains look

like letter N. Made development more difficult.

User Study Demoed in Chem 35.01 last week Lab sessions open to students

4 sessions a week starting last week. Students complete a worksheet using

ChemPad. 28 students so far. Can make up to

29 spaces available per session. Personal invites to 55 students.

User Study Getting feedback about whether or not

ChemPad is accomplishing its goals. Students complete a survey at the end of a

session. Gives the development team feedback on

usability. Gives us anecdotal evidence of pedagogical

value. Comparing quiz scores of students who do and

don’t use ChemPad. Comparing only scores on 3D questions.

User Responses It's pretty cool. It's cool how you can draw a molecule in 2D and have

it represented in 3D. I like being able to flip the molecules to see it in the

right orientation. Having a 3-D representation of the molecule for

learning purposes is extremely helpful...much better than on paper

I like that it shows the C.I.P. numbering so that you can see if it is clockwise or counter-clockwise very easily.

It helped me understand rotation better. It also helped me visualize which atoms were stereocenters.

Future Work General Chemistry Interface.

Multistroke “normal” input. Recognize entire drawing at end of input.

Expanding Notational Vocabulary. More elements. More notations such as charges.

More visualizations for students. Allow for larger molecules. Combine with other tablet software such as

MathPad.

Acknowledgements Special Thanks To:

Professor Matthew Zimmt Sascha Becker Loring Holden Bob Zeleznik Professor Andries van Dam

Funders & Donors: Atlantic Philanthropies HP