TEMPLATES¶

In [1]:

%%time
from retropaths.reactions.template import ReactionTemplate
from retropaths.reactions.changes import Changes
from retropaths.reactions.rules import Rules
from retropaths.reactions.conditions import Conditions, Acidity, Solvent
from ipywidgets import interact
from IPython.core.display import HTML
import retropaths.helper_functions as hf
from retropaths.molecules.molecule import Molecule
import itertools
from retropaths.reactions.template_utilities import template_generator, special_cartesian_product

library = hf.pload('../data/reactions.p')

HTML('<script src="//d3js.org/d3.v3.min.js"></script>')

%%time from retropaths.reactions.template import ReactionTemplate from retropaths.reactions.changes import Changes from retropaths.reactions.rules import Rules from retropaths.reactions.conditions import Conditions, Acidity, Solvent from ipywidgets import interact from IPython.core.display import HTML import retropaths.helper_functions as hf from retropaths.molecules.molecule import Molecule import itertools from retropaths.reactions.template_utilities import template_generator, special_cartesian_product library = hf.pload('../data/reactions.p') HTML('')

CPU times: user 6.22 s, sys: 625 ms, total: 6.85 s
Wall time: 6.99 s

Out[1]:

MATCHING GROUPS¶

In [2]:

# The library of templates is built around a matching_group_data object
mg = library.matching
print(mg)

# The library of templates is built around a matching_group_data object mg = library.matching print(mg)

Matching groups loaded:
(H+, Hydrogen cation) (O, Water) (HCl, Chloridic Acid) (A1AA1, 3-membered-ring) (A1A=A1, 3-membered cyclopropene) (A1AAA1, 4-membered-ring) (A1AAAA1, 5-membered-ring) (A1A=AA1, A-Cyclobutene) (A1A(ar)AA1, A-Cyclobutene-Aromatic) (a1A=Aa1, A-Cyclobutadiene) (a1A(ar)Aa1, A-Cyclobutadiene) (A1A(ar)A(ar)A1, A-Cyclobutadiene) (A1AA=AA1, A-Cyclopentene) (A1AA(ar)AA1, A-Cyclo-aromatic-5) (A1=AA=AA1, A-Cyclopentadiene) (A1=AA(ar)AA1, A-Cyclopentene-Aromatic) (A1(ar)AA(ar)AA1, A-Cyclo-Double-Aromatic-pentene) (A1(ar)A(ar)AAA1, bridged_meta_tether_2) (A1(ar)A(ar)AA=A1, A-Cyclo-Double-Aromatic-Pentene3) (A1(ar)A(ar)A(ar)AAA1, bridged_para_tether_2) (A1(ar)A(ar)A(ar)AAAA1, bridged_para_tether_3) (A1(ar)A(ar)A(ar)AAAAA1, bridged_para_tether_4) (A1(ar)A(ar)A(ar)AAAAAA1, bridged_para_tether_5) (A1(ar)A(ar)AA1, bridged_meta_tether_1) (A1(ar)A(ar)AAAA1, bridged_meta_tether_3) (A1(ar)A(ar)AAAAA1, bridged_meta_tether_4) (A1(ar)A(ar)AAAAAA1, bridged_meta_tether_5) (A1LA1, 3-membered-ring-L) (LH, Hydrogen) (MeL, Methyl) (PhL, Phenyl) (OHL, Hydroxyl) (FL, Fluorine) (ClL, Chlorine) (BrL, Bromine) (IL, Iodine) (C(L)(=CR2), Alkene-R) ((C=O)[L][R], Carbonyl) (C(=O)(OR)[L], Carboxyl) (C(=O)(OL)[R], Carboxyl-H) (C#N[L], Nitrile) (S([L])[R], Thiolate) (O([L])[R], Alkoxide) (RCOL, Long-Alkoxide) ([N-]=[N+]=N[L], Azide) (NR3L, Ammonia) (PR3L, Phosphine) (PR2L, Phosphine) (NR2L, Amino) (NO2L, Nitrite) ([N+]O2L, Nitronium) (NO3[L], Nitrate) (ONOL, ONO) (NOL, Nitroso) (CONR2L, Amide) (CONRRL, N-Amide) (C=ONR2OL, O-Carbamate) (C=OORNRL, N-Carbamate) ((S=O)[L][R], Sulfoxide) (OSO2[L], Sulfonate) (LSO2R, Sulfonyl) (HSO4[L], Sulfate) (SO4[L], Sulfate) (C(=O)[R][L], Acetyl) (LOSO2[R], Sulfonate) (R, Alkane) (RCL, Long-Alkane) (RCL-, Long-Alkane-(-)) (Ar-6C, Aryl-Phenyl) (ArL, Aryl-Phenyl) (CO-(=C), Enolate) (COH(=C), Enol) (OL-, Alkoxide-) (H2NCOOL, Carbamic Acid) (C(=O)(OL)(OR), Carbonate-Ester) (LP(=O)(OR)2, Phosphonate) (C(=S)(SR)[L], Dithioate) (C(=S)(SL)[R], Dithioate-H) (LOOH, Peroxide) (LOOR, Peroxide) (SO2RNRL, Sulfonamide) ([O+]([H])([H])[L], Water-Lg) (H2OL+, Water-Lg) ([O+]([H])([R])[L], Alcohol) (OR2L+, Ether) (RCOHL+, Long-Protonated-Alkoxide) (C(=O)[O+]([L])[H], Protonated-Carboxyl-H) (C=[O+][L], Protonated-Carbonyl) (C(=[O+][L])N, Protonated-Amide) (C=NL+, Protonated-Iminium) (HL+, H+) (C, Carbon) (C-Aromatic, Aromatic Carbon) (OCZ, Ester-Oxygen) (CZZZL, Carbon) (NZZL, Nitrogen) (OZL, Oxygen) (OHZ, Alcohol) (C(=O)(L)Z, Carbonyl Carbon) (C-Alkene, Alkene Carbon) (C-Imine, Imine Carbon) (C-Alkyne, Alkyne Carbon) (C-Nitrile, Nitrile Carbon) (SZL, Sulfur) (PZL, Phosphorus) (HL, H) (CA3L, A-Aliphatic-Carbon) (CA2L, A-Aromatic-Carbon) (AL-aromatic, L-aromatic) (AL, L-A) (CA2VL, Vinyl-Group) (CA2VL-no-O, Vinyl-Group-No-Oxygen) (CCAL, A-Carbon=Carbon) (COAL, A-Oxygen=Carbon) (CNAL, A-Nitrogen=Carbon) (NA2L, A-Aliphatic-Nitrogen) (OAL, A-Aliphatic-Oxygen) (O([L])[A], A-Alkoxide) (C(=O)(L)A, A-Carbonyl) (L-CCC=O, Gamma-Carbonyl) (L-ArCCC=O, Aromatic-Gamma-Carbonyl) (L-CC=O, Beta-Carbonyl2) (L-CO, Beta-Alcohol) (L-CCO, Gamma-Alcohol) (L-CS, Beta-Alcohol) (L-CCS, Gamma-Thiol) (L-CN, Beta-Amine) (L-CCN, Gamma-Amine) (CX3L, Halocarbon) 

In [3]:

#  mg.draw(label)   <- this draws the single matching group. Let's use an interactive function.

@interact(label=list(mg.data.keys()))
def draw_matching(label):
    single_matching_group = mg.data[label]
    print(f'Matching group: {single_matching_group}')
    return mg.draw(label)

# mg.draw(label) <- this draws the single matching group. Let's use an interactive function. @interact(label=list(mg.data.keys())) def draw_matching(label): single_matching_group = mg.data[label] print(f'Matching group: {single_matching_group}') return mg.draw(label)

interactive(children=(Dropdown(description='label', options=('H+', 'O', 'HCl', 'A1AA1', 'A1A=A1', 'A1AAA1', 'A…

CONDITIONS¶

In [4]:

cond = Conditions()  # I create the default conditions
cond

cond = Conditions() # I create the default conditions cond

Out[4]:

Acidity all_pH | Solvent any

In [5]:

acid_water = Conditions(pH=Acidity.acid, solvent=Solvent.water)  # those one are acid and water.
acid_water

acid_water = Conditions(pH=Acidity.acid, solvent=Solvent.water) # those one are acid and water. acid_water

Out[5]:

Acidity acid | Solvent water

In [6]:

acid_water.is_compatible(cond)  # <- watch out this is NOT COMMUTATIVE. An Acid/Water pot is NOT compatible with an "any" pot.

acid_water.is_compatible(cond) # <- watch out this is NOT COMMUTATIVE. An Acid/Water pot is NOT compatible with an "any" pot.

Out[6]:

False

In [7]:

cond.is_compatible(acid_water)  # <- the reverse is true, an "any" pot can be Acid/Water

cond.is_compatible(acid_water) # <- the reverse is true, an "any" pot can be Acid/Water

Out[7]:

True

MOLECULES with R groups¶

In [8]:

a = Molecule.from_smiles('C1(C2=C(C(N1C)=O)C=CC=C2)=O')
b = Molecule.from_smiles('NN')
mol = a + b
mol.draw(mode='d3')

a = Molecule.from_smiles('C1(C2=C(C(N1C)=O)C=CC=C2)=O') b = Molecule.from_smiles('NN') mol = a + b mol.draw(mode='d3')

Out[8]:

In [9]:

# We can add R groups using the substitute_groups method. It takes as input a list of substitutions.
reactants = mol.substitute_groups([[12, 'R1'],
                                   [15, 'R2'],
                                   [16, 'R3'],
                                   [17, 'R4'],
                                   [18, 'R15']])  # NOTE: we call one R group 'R15', names do not matter (as long as they're not repeated)
reactants.draw(mode='d3')

# We can add R groups using the substitute_groups method. It takes as input a list of substitutions. reactants = mol.substitute_groups([[12, 'R1'], [15, 'R2'], [16, 'R3'], [17, 'R4'], [18, 'R15']]) # NOTE: we call one R group 'R15', names do not matter (as long as they're not repeated) reactants.draw(mode='d3')

Out[9]:

RULES¶

In [10]:

rules = Rules()  # create the Rules object
rules.add_new_R_pattern_to_enforce_rule('R1', ['HL', 'CA3L'], mg)  # Add an enforce for R1 to be HL or CA3L matching groups
rules

rules = Rules() # create the Rules object rules.add_new_R_pattern_to_enforce_rule('R1', ['HL', 'CA3L'], mg) # Add an enforce for R1 to be HL or CA3L matching groups rules

Out[10]:

Condition to enforce:

R1 = H, A-Aliphatic-Carbon

CHANGES¶

In [11]:

dic_changes = {'delete': [(19, 21), (20, 23), (0, 4), (3, 4)],
               'single': [(0, 19), (3, 20), (4, 21), (4, 23)],
               'double': [],
               'aromatic': [],
               'triple': [],
               'charges': []}

changes = Changes.from_dict(dic_changes)
changes

dic_changes = {'delete': [(19, 21), (20, 23), (0, 4), (3, 4)], 'single': [(0, 19), (3, 20), (4, 21), (4, 23)], 'double': [], 'aromatic': [], 'triple': [], 'charges': []} changes = Changes.from_dict(dic_changes) changes

Out[11]:

Changes:

Bonds:
delete -> [(19, 21), (20, 23), (0, 4), (3, 4)]
single -> [(0, 19), (3, 20), (4, 21), (4, 23)]

In [12]:

# changes can be APPLIED to a molecule.
# NOTE: This function is NOT giving you all the regioisomers!!! This just update the exact bonds that are in the changes.
new_mol = reactants.update_edges_and_charges(changes)
Molecule.draw_list([reactants, new_mol], names=['Reactant molecule', 'Product after application'])

# changes can be APPLIED to a molecule. # NOTE: This function is NOT giving you all the regioisomers!!! This just update the exact bonds that are in the changes. new_mol = reactants.update_edges_and_charges(changes) Molecule.draw_list([reactants, new_mol], names=['Reactant molecule', 'Product after application'])

Out[12]:

Reactant molecule

Product after application

THE REACTION TEMPLATE¶

we now have all the pieces to build a reaction template.¶

In [13]:

rt = ReactionTemplate.from_components('Reaction name goes here',
                                      reactants,
                                      dic_changes,
                                      acid_water,
                                      rules=rules,
                                      MG=mg)
rt.draw(size=(400, 400))

rt = ReactionTemplate.from_components('Reaction name goes here', reactants, dic_changes, acid_water, rules=rules, MG=mg) rt.draw(size=(400, 400))

Out[13]:

Reaction name goes here

References: 0

Condition to enforce:

R1 = H, A-Aliphatic-Carbon

Reactants

Products

In [14]:

# let's take a new molecule now
# NOTE this molecules DOES NOT give you any products, because it breaks the rules. Cl is NOT H nor an aliphatic carbon.
mol = Molecule.from_smiles('NN.C1(C2=C(C(N1CCl)=O)C=CC=C2)=O')
prod = rt.apply_forward(mol)
Molecule.draw_list([mol] + prod, names=['Reactants'] + ['Products']*len(prod))

# let's take a new molecule now # NOTE this molecules DOES NOT give you any products, because it breaks the rules. Cl is NOT H nor an aliphatic carbon. mol = Molecule.from_smiles('NN.C1(C2=C(C(N1CCl)=O)C=CC=C2)=O') prod = rt.apply_forward(mol) Molecule.draw_list([mol] + prod, names=['Reactants'] + ['Products']*len(prod))

Out[14]:

Reactants

In [15]:

# other Rs substitutions are not restricted, so mol2 actually gets a product
mol2 = Molecule.from_smiles('NN.C1(C2=C(C(N1C)=O)C=C(Cl)C=C2)=O')
prod2 = rt.apply_forward(mol2)
Molecule.draw_list([mol2] + prod2, names=['Reactants'] + [f'Product {i+1}' for i, _ in enumerate(prod2)])

# other Rs substitutions are not restricted, so mol2 actually gets a product mol2 = Molecule.from_smiles('NN.C1(C2=C(C(N1C)=O)C=C(Cl)C=C2)=O') prod2 = rt.apply_forward(mol2) Molecule.draw_list([mol2] + prod2, names=['Reactants'] + [f'Product {i+1}' for i, _ in enumerate(prod2)])

Out[15]:

Reactants

Product 1

The save method is very important, because it does some basic tests and precalculates the list of changes.¶

When the template is saved, Rs are remapped, tests are run and regioisomers are calculated.

In [16]:

# if you uncomment and run this cell, the template rt is serialized in the hard disk in '.' folder.
# rt.save()

# if you uncomment and run this cell, the template rt is serialized in the hard disk in '.' folder. # rt.save()

this is what happens when you save.¶

1. Rs are remapped

In [17]:

rt.rename_rs_from_map()  # Note how R15 is now R5
rt.draw()

rt.rename_rs_from_map() # Note how R15 is now R5 rt.draw()

Out[17]:

Reaction name goes here

References: 0

Condition to enforce:

R1 = H, A-Aliphatic-Carbon

Reactants

Products

Regioisomers precalculation¶

The template is created with a single change object, but all the regioisomers are precalculated when the template is created. Products and changes from products to reactants are calculated as well.

In [18]:

reaction_name = "A new template with some regioselectivity"
conditions = Conditions()
rules = Rules()

a = Molecule.from_smiles('OCCN')
b = Molecule.from_smiles('N(O)(=O)')
p_precursor = (a + b).substitute_groups([[5, 'R1'], [6, 'R2'], [7, 'R3'], [8, 'R4']])

changes_d = {'delete': [(0, 4), (1, 6), (2, 3), (3, 9), (3, 10), (11, 13), (11, 12)], 'single': [(2, 6), (4, 12), (9, 13), (10, 13)], 'double': [(0, 1)], 'aromatic': [], 'triple': [(3, 11)], 'charges': []}

reaction_template = ReactionTemplate.from_components(reaction_name, p_precursor, changes_d, conditions, rules=rules, MG=mg)
reaction_template.draw(mode='d3', size=(300, 300), node_index=True)

reaction_name = "A new template with some regioselectivity" conditions = Conditions() rules = Rules() a = Molecule.from_smiles('OCCN') b = Molecule.from_smiles('N(O)(=O)') p_precursor = (a + b).substitute_groups([[5, 'R1'], [6, 'R2'], [7, 'R3'], [8, 'R4']]) changes_d = {'delete': [(0, 4), (1, 6), (2, 3), (3, 9), (3, 10), (11, 13), (11, 12)], 'single': [(2, 6), (4, 12), (9, 13), (10, 13)], 'double': [(0, 1)], 'aromatic': [], 'triple': [(3, 11)], 'charges': []} reaction_template = ReactionTemplate.from_components(reaction_name, p_precursor, changes_d, conditions, rules=rules, MG=mg) reaction_template.draw(mode='d3', size=(300, 300), node_index=True)

Out[18]:

A new template with some regioselectivity

References: 0

Reactants

Products

In [19]:

# NOTE: the changes_react_to_prod is 2 long!!
# We told the program that R2-C bond should be broken, but the program recognized that this template should apply for R1, too!!!
reaction_template.changes_react_to_prod

# NOTE: the changes_react_to_prod is 2 long!! # We told the program that R2-C bond should be broken, but the program recognized that this template should apply for R1, too!!! reaction_template.changes_react_to_prod

Out[19]:

[Changes(bonds=BondsChanges(delete=[(0, 4), (1, 6), (2, 3), (3, 9), (3, 10), (11, 13), (11, 12)], single=[(2, 6), (4, 12), (9, 13), (10, 13)], aromatic=[], double=[(0, 1)], triple=[(3, 11)]), charges=ChargeChanges(charges=[])),
 Changes(bonds=BondsChanges(delete=[(0, 4), (1, 5), (2, 3), (3, 9), (3, 10), (11, 13), (11, 12)], single=[(2, 5), (4, 12), (9, 13), (10, 13)], aromatic=[], double=[(0, 1)], triple=[(3, 11)]), charges=ChargeChanges(charges=[]))]

In [20]:

# From product to reactants, there are 3 identical possibilities. R2, R3 and R4 are identical. Those are also precalculated.
reaction_template.changes_prod_to_react

# From product to reactants, there are 3 identical possibilities. R2, R3 and R4 are identical. Those are also precalculated. reaction_template.changes_prod_to_react

Out[20]:

[Changes(bonds=BondsChanges(delete=[(2, 8), (4, 12), (9, 13), (10, 13), (3, 11)], single=[(0, 4), (1, 8), (2, 3), (3, 9), (3, 10), (11, 12), (0, 1)], aromatic=[], double=[(11, 13)], triple=[]), charges=ChargeChanges(charges=[])),
 Changes(bonds=BondsChanges(delete=[(2, 6), (4, 12), (9, 13), (10, 13), (3, 11)], single=[(0, 4), (1, 6), (2, 3), (3, 9), (3, 10), (11, 12), (0, 1)], aromatic=[], double=[(11, 13)], triple=[]), charges=ChargeChanges(charges=[])),
 Changes(bonds=BondsChanges(delete=[(2, 7), (4, 12), (9, 13), (10, 13), (3, 11)], single=[(0, 4), (1, 7), (2, 3), (3, 9), (3, 10), (11, 12), (0, 1)], aromatic=[], double=[(11, 13)], triple=[]), charges=ChargeChanges(charges=[]))]

DEBUG¶

In [21]:

# this is what happens when you try to save an invalid reaction template.
# NOTE, the "empty changes teplate" would apply infinite times.
dic_changes2 = {'delete': [], 
                'single': [], 
                'double': [], 
                'aromatic': [], 
                'triple': [], 
                'charges': []}  # <- Empty Changes

rt = ReactionTemplate.from_components('Reaction_name_goes_here', reactants, dic_changes2, acid_water, rules=rules, MG=mg)

try:
    rt.default_test()  # <- This will fail, because Products and reactants are the same molecules.
except AssertionError as e:
    raise hf.StopExecution(e)  # <- suppresses verbose output.

# this is what happens when you try to save an invalid reaction template. # NOTE, the "empty changes teplate" would apply infinite times. dic_changes2 = {'delete': [], 'single': [], 'double': [], 'aromatic': [], 'triple': [], 'charges': []} # <- Empty Changes rt = ReactionTemplate.from_components('Reaction_name_goes_here', reactants, dic_changes2, acid_water, rules=rules, MG=mg) try: rt.default_test() # <- This will fail, because Products and reactants are the same molecules. except AssertionError as e: raise hf.StopExecution(e) # <- suppresses verbose output.

In [22]:

dic_changes2 = {'delete': [(1, 2)], 
                'single': [],
                'double': [], 
                'aromatic': [], 
                'triple': [], 
                'charges': []}  # <- Not empty anymore
rt = ReactionTemplate.from_components('Reaction_name_goes_here', reactants, dic_changes2, acid_water, rules=rules, MG=mg)  # <- this would be a stupid template

rt.products.nodes[10]['charge'] = 100  # let's mess with the total charge.
rt.save()  # <- nah, I will not save this!

dic_changes2 = {'delete': [(1, 2)], 'single': [], 'double': [], 'aromatic': [], 'triple': [], 'charges': []} # <- Not empty anymore rt = ReactionTemplate.from_components('Reaction_name_goes_here', reactants, dic_changes2, acid_water, rules=rules, MG=mg) # <- this would be a stupid template rt.products.nodes[10]['charge'] = 100 # let's mess with the total charge. rt.save() # <- nah, I will not save this!

Basic test failed. Template Reaction_name_goes_here has been NOT written to disc.

In [23]:

# Identical Rs MUST have the same rules applied to them. If this is not the case, it means that the template should be changed!!

reaction_name = "A_new_template_with_some_regioselectivity"
conditions = Conditions()
rules = Rules()

# R1 and R2 are identical R groups, but I add a restriction Rule ONLY to R1 !
rules.add_new_R_pattern_to_enforce_rule('R1', ['HL', 'CA3L'], mg)

a = Molecule.from_smiles('OCCN')
b = Molecule.from_smiles('N(O)(=O)')
p_precursor = (a + b).substitute_groups([[5, 'R1'], [6, 'R2'], [7, 'R3'], [8, 'R4']])

changes_d = {'delete': [(0, 4), (1, 6), (2, 3), (3, 9), (3, 10), (11, 13), (11, 12)],
             'single': [(2, 6), (4, 12), (9, 13), (10, 13)],
             'double': [(0, 1)],
             'aromatic': [],
             'triple': [(3, 11)],
             'charges': [],
            }

reaction_template = ReactionTemplate.from_components(reaction_name, p_precursor, changes_d, conditions, rules=rules, MG=mg)

reaction_template.draw(size=(600,600))  # NOTE: The program WILL temporary create the template, so it is possible to visualize and change it

# Identical Rs MUST have the same rules applied to them. If this is not the case, it means that the template should be changed!! reaction_name = "A_new_template_with_some_regioselectivity" conditions = Conditions() rules = Rules() # R1 and R2 are identical R groups, but I add a restriction Rule ONLY to R1 ! rules.add_new_R_pattern_to_enforce_rule('R1', ['HL', 'CA3L'], mg) a = Molecule.from_smiles('OCCN') b = Molecule.from_smiles('N(O)(=O)') p_precursor = (a + b).substitute_groups([[5, 'R1'], [6, 'R2'], [7, 'R3'], [8, 'R4']]) changes_d = {'delete': [(0, 4), (1, 6), (2, 3), (3, 9), (3, 10), (11, 13), (11, 12)], 'single': [(2, 6), (4, 12), (9, 13), (10, 13)], 'double': [(0, 1)], 'aromatic': [], 'triple': [(3, 11)], 'charges': [], } reaction_template = ReactionTemplate.from_components(reaction_name, p_precursor, changes_d, conditions, rules=rules, MG=mg) reaction_template.draw(size=(600,600)) # NOTE: The program WILL temporary create the template, so it is possible to visualize and change it

Out[23]:

A_new_template_with_some_regioselectivity

References: 0

Condition to enforce:

R1 = H, A-Aliphatic-Carbon

Reactants

Products

In [24]:

# but, you guess it, this template will NOT be saved until it passes all tests.
try:
    reaction_template.save()
except AssertionError as e:
    raise hf.StopExecution(e)

# but, you guess it, this template will NOT be saved until it passes all tests. try: reaction_template.save() except AssertionError as e: raise hf.StopExecution(e)

Template Generator¶

In [25]:

# First create the template with special characters like "Nu" and "Lg"
reaction_name = "Example Template Generator"

doi_list = ['http://www1.biologie.uni-hamburg.de/b-online/library/newton/Chy251_253/Lectures/Sn2LeavingGroups/Sn2LeavingGroups.html',
            'https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Organic_Chemistry_-_A_Carbonyl_Early_Approach_(McMichael)/01%3A_Chapters/1.24%3A_Nucleophilic_Substitution_SN2_SN1',
            'http://www1.biologie.uni-hamburg.de/b-online/library/newton/Chy251_253/Lectures/Sn2LeavingGroups/Sn2LeavingGroups.html',
            ]
conditions_thing = {'temperature': 3,
                    'light': False,
                    'pH': 4,
                    'solvent': Solvent.no_water,
                    'catalyst': '',
                    'doi': doi_list}
conditions = Conditions(**conditions_thing)

a = Molecule.from_smiles('[HH]')  # electrophile
b = Molecule.from_smiles("[HH]")  # nucleophile
p_without_r = b + a

p1_precursor = p_without_r.substitute_groups([[1, 'Nu'], [3, 'Lg'], [2, 'R1']])

changes_d = {'delete': [(2, 3), (0, 1)],
             'single': [(0, 3), (1, 2)],
             'double': [],
             'aromatic': [],
             'triple': [],
             'charges': []}

rules = Rules()

prova = ReactionTemplate.from_components(reaction_name, p1_precursor, changes_d, conditions, rules=rules, MG=mg)
prova.draw(size=(300, 600), charges=True, node_index=True)

# First create the template with special characters like "Nu" and "Lg" reaction_name = "Example Template Generator" doi_list = ['http://www1.biologie.uni-hamburg.de/b-online/library/newton/Chy251_253/Lectures/Sn2LeavingGroups/Sn2LeavingGroups.html', 'https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Organic_Chemistry_-_A_Carbonyl_Early_Approach_(McMichael)/01%3A_Chapters/1.24%3A_Nucleophilic_Substitution_SN2_SN1', 'http://www1.biologie.uni-hamburg.de/b-online/library/newton/Chy251_253/Lectures/Sn2LeavingGroups/Sn2LeavingGroups.html', ] conditions_thing = {'temperature': 3, 'light': False, 'pH': 4, 'solvent': Solvent.no_water, 'catalyst': '', 'doi': doi_list} conditions = Conditions(**conditions_thing) a = Molecule.from_smiles('[HH]') # electrophile b = Molecule.from_smiles("[HH]") # nucleophile p_without_r = b + a p1_precursor = p_without_r.substitute_groups([[1, 'Nu'], [3, 'Lg'], [2, 'R1']]) changes_d = {'delete': [(2, 3), (0, 1)], 'single': [(0, 3), (1, 2)], 'double': [], 'aromatic': [], 'triple': [], 'charges': []} rules = Rules() prova = ReactionTemplate.from_components(reaction_name, p1_precursor, changes_d, conditions, rules=rules, MG=mg) prova.draw(size=(300, 600), charges=True, node_index=True)

Out[25]:

Example Template Generator

References: 0,1,2

Reactants

Products

In [26]:

# Now define lists of matching groups for those special characters

Lg = ['IL', 'BrL', 'ClL', 'LOSO2[R]']
Nu = ['C#N[L]', 'S([L])[R]', 'NR2L', 'O([L])[R]', 'OHL']

product = list(itertools.product(Lg, Nu))

# Can define a reactivity order e.g. upper diagonal of matrix
combos = special_cartesian_product(product)


bs = ''
repl_list = [[('Lg', combo[0]), ('Nu', combo[1])] for combo in combos if combo[0] != combo[1]]

changes = Changes.from_dict(changes_d)
a = template_generator(p1_precursor, changes, repl_list, mg)

for (lg, nu), name, p1, changes in zip(repl_list, *a):
    conditions.solvent = Solvent.no_water

    full_name = reaction_name + '-' + name
    rules = Rules.create_default_rules_for_molecule(p1, mg, allow_aromatic=True)
    rules.add_new_R_pattern_to_enforce_rule('R1', ['CA3L'], mg)

    if nu[1] == 'S([L])[R]':
        rules.add_new_R_pattern_to_enforce_rule('R16', ['CA3L', 'CA2L'], mg)

    # more rules can be added here

    prova = ReactionTemplate.from_components(full_name, p1, changes.to_dict(), conditions, rules=rules, MG=mg)
    # prova.save(folder=saving_folder)
    bs += prova.draw(size=(400, 400), mode='d3', node_index=True, charges=True, string_mode=True)
HTML(bs)

# Now define lists of matching groups for those special characters Lg = ['IL', 'BrL', 'ClL', 'LOSO2[R]'] Nu = ['C#N[L]', 'S([L])[R]', 'NR2L', 'O([L])[R]', 'OHL'] product = list(itertools.product(Lg, Nu)) # Can define a reactivity order e.g. upper diagonal of matrix combos = special_cartesian_product(product) bs = '' repl_list = [[('Lg', combo[0]), ('Nu', combo[1])] for combo in combos if combo[0] != combo[1]] changes = Changes.from_dict(changes_d) a = template_generator(p1_precursor, changes, repl_list, mg) for (lg, nu), name, p1, changes in zip(repl_list, *a): conditions.solvent = Solvent.no_water full_name = reaction_name + '-' + name rules = Rules.create_default_rules_for_molecule(p1, mg, allow_aromatic=True) rules.add_new_R_pattern_to_enforce_rule('R1', ['CA3L'], mg) if nu[1] == 'S([L])[R]': rules.add_new_R_pattern_to_enforce_rule('R16', ['CA3L', 'CA2L'], mg) # more rules can be added here prova = ReactionTemplate.from_components(full_name, p1, changes.to_dict(), conditions, rules=rules, MG=mg) # prova.save(folder=saving_folder) bs += prova.draw(size=(400, 400), mode='d3', node_index=True, charges=True, string_mode=True) HTML(bs)

Out[26]:

Example Template Generator-Lg-Iodine-and-Nu-Nitrile

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon

Reactants

Products

Example Template Generator-Lg-Iodine-and-Nu-Thiolate

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R16 = A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Iodine-and-Nu-Amino

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R21 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon
R22 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Iodine-and-Nu-Alkoxide

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R17 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Iodine-and-Nu-Hydroxyl

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon

Reactants

Products

Example Template Generator-Lg-Bromine-and-Nu-Nitrile

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon

Reactants

Products

Example Template Generator-Lg-Bromine-and-Nu-Thiolate

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R16 = A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Bromine-and-Nu-Amino

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R21 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon
R22 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Bromine-and-Nu-Alkoxide

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R17 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Bromine-and-Nu-Hydroxyl

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon

Reactants

Products

Example Template Generator-Lg-Chlorine-and-Nu-Nitrile

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon

Reactants

Products

Example Template Generator-Lg-Chlorine-and-Nu-Thiolate

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R16 = A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Chlorine-and-Nu-Amino

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R21 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon
R22 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Chlorine-and-Nu-Alkoxide

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R17 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Chlorine-and-Nu-Hydroxyl

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon

Reactants

Products

Example Template Generator-Lg-Sulfonate-and-Nu-Nitrile

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R23 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Sulfonate-and-Nu-Thiolate

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R16 = A-Aliphatic-Carbon, A-Aromatic-Carbon
R23 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Sulfonate-and-Nu-Amino

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R21 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon
R22 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon
R23 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Sulfonate-and-Nu-Alkoxide

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R17 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon
R23 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

Example Template Generator-Lg-Sulfonate-and-Nu-Hydroxyl

References: 0,1,2

Condition to enforce:

R1 = A-Aliphatic-Carbon
R23 = H, A-Aliphatic-Carbon, A-Aromatic-Carbon

Reactants

Products

In [ ]: