1. Mol Orb Reactivity Proposal Reaction Mixture Mol Orb Enumerator
Molecular
Orbital List
Reduced
Mol Orb List
Stopping
Criteria
Analyzer
Mol Orb
Compatibility
Scoring
Revised
Reaction
Mixture
Scored Orbital
Compatibility List
Reactor
Iterator
ReactionSimulator.runSimulation

2. Reaction Mixture 100 100 10 Reaction Conditions Solvent Properties
Temperature
ReactionSimulator.ReactionMixture

3. Orbital Enumerator
Largely done for core atoms, but need extra logic to handle
S,P atoms (d orbitals)
Resonance structure enumerator
Extended orbital chaining (e.g., E2, Sn2’)
Orbital Reactivity Proposal
Before full combinatorial reactivity compatibility check, pre-filter orbital list to exclude those are very unlikely to react
OrbitalModel.orbitalIter
OrbitalScore.OrbitalReactivityProbability

4. Molecular Orbital List
Filled
sp2 O
p CO …
Unfilled
p* CO
s* HC  p* CO
Filled
sp3 O
s CO …
Unfilled
s* HO
s* CO
Filled
sp3 O
sp2 O …
Unfilled
p* SO
s* HO  p* SO

5. Orbital Reactivity / Compatibility
Core challenge (rest is mostly accounting)
Thermodynamic Scoring
Relative energy / stability of structures
Reaction conditions may influence (particularly stabilization of ions by solvation)
Components like bond energies, ring strain, entropy, aromaticity, conjugation and resonance, hyperconjugation, formal charges, octet rule
ReactionScore.FreeEnergy

6. Orbital Reactivity / Compatibility
Kinetics / Transition State Scoring
Estimated barrier to structures to react based on proposed orbital interaction
Thermodynamic basis + Klopman-Salem components like sterics, ionic character vs. orbital coefficients (HOMO-LUMO energies)
Entropy considerations (number of molecules, rotatable bonds)
OrbitalScore.TransitionStateEnergy

7. Scored Orbital Compatibility List
sp2 O (reactant 1)  s* HO (reactant 3) ~ 2 kcal / mol
sp3 O (reactant 2)  s* HO (reactant 3) ~ 3 kcal / mol …

8. Reactor Iterator Orbital Interaction Applicator
Mostly done for core orbital interactions
Generate / translate to curved arrows
Need to implement stereospecificity logic
Concentration / Prevalence model
Use reactivity scores x concentrations to calculate probabilities on likely mechanistic steps (elementary reactions)
Apply mechanistic steps to update reaction mix, but limit achievable transition states by reaction temperature
???
ReactionSimulator

9. Revised Reaction Mixture97 94 1 3 6 9

10. GUI Input of reaction mixtures Output of resulting reaction mixtures
Traceback of core mechanistic steps of major products
Qualitative free energy diagrams from tracebacks
Interactive exploration / explanation. Select mixtures or orbital combinations to see systems score report
Systems bio style tracking of molecule concentrations over time (iterations)
???
Separate from reaction directory? Leave that for tutorial material?

11. Proposed Reaction Predictor
Proposes complete arrow-pushing mechanisms,
Including reaction intermediates and
Electron flow schematics
Qualitative reaction energy coordinate diagrams
Benchmark: Solve problems that human experts can on paper
Relative Energy
DG‡ DG
Reaction Coordinate +