chython · kochern · Nov 18, 2025 · Nov 18, 2025 · Nov 18, 2025 · Nov 19, 2025
diff --git a/chython/algorithms/fingerprints/morgan.py b/chython/algorithms/fingerprints/morgan.py
@@ -40,7 +40,7 @@ def morgan_fingerprint(self, min_radius: int = 1, max_radius: int = 4,
         :param min_radius: minimal radius of EC
         :param max_radius: maximum radius of EC
         :param length: bit string's length. Should be power of 2
-        :param number_active_bits: number of active bits for each hashed tuple
+        :param number_active_bits: number of active bits for each hashed tuple (int or 'auto'). For 'auto' option, number of bits is count of each hash + 1.
 
         :return: array(n_features)
         """
@@ -57,20 +57,30 @@ def morgan_bit_set(self, min_radius: int = 1, max_radius: int = 4,
         :param min_radius: minimal radius of EC
         :param max_radius: maximum radius of EC
         :param length: bit string's length. Should be power of 2
-        :param number_active_bits: number of active bits for each hashed tuple
+        :param number_active_bits: number of active bits for each hashed tuple (int or 'auto'). For 'auto' option, number of bits is count of each hash + 1.
         """
         mask = length - 1
         log = int(log2(length))
 
         active_bits = set()
-        for tpl in self.morgan_hash_set(min_radius, max_radius):
-            active_bits.add(tpl & mask)
-            if number_active_bits == 2:
-                active_bits.add(tpl >> log & mask)
-            elif number_active_bits > 2:
-                for _ in range(1, number_active_bits):
-                    tpl >>= log
-                    active_bits.add(tpl & mask)
+
+        if number_active_bits == 'auto':
+            for hsh, cnt in self.morgan_hash_counts(min_radius, max_radius):
+                active_bits.add(hsh & mask)
+                active_bits.add(hsh >> log & mask)
+                for _ in range(cnt-1):
+                    hsh >>= log
+                    active_bits.add(hsh & mask)
+
+        else:
+            for tpl in self.morgan_hash_set(min_radius, max_radius):
+                active_bits.add(tpl & mask)
+                if number_active_bits == 2:
+                    active_bits.add(tpl >> log & mask)
+                elif number_active_bits > 2:
+                    for _ in range(1, number_active_bits):
+                        tpl >>= log
+                        active_bits.add(tpl & mask)
         return active_bits
 
     def morgan_hash_set(self: 'MoleculeContainer', min_radius: int = 1, max_radius: int = 4) -> Set[int]:
@@ -129,6 +139,38 @@ def _morgan_hash_dict(self: 'MoleculeContainer', min_radius: int = 1, max_radius
             out.append(identifiers)
         return out[-(max_radius - min_radius + 1):]  # slice [min, max] radii range
 
+    def morgan_hash_counts(self, min_radius: int = 1, max_radius: int = 4) -> List[tuple]:
+        """
+        Count occurrences of each hash from _morgan_hash_dict.
+
+        :param min_radius: minimal radius of EC
+        :param max_radius: maximum radius of EC
+        :return: list of (hash, count) tuples
+        """
+        counts = defaultdict(int)
+        for hash_dict in self._morgan_hash_dict(min_radius, max_radius):
+            for h in hash_dict.values():
+                counts[h] += 1
+        return list(counts.items())
+
+    def morgan_count_fingerprint(self, min_radius: int = 1, max_radius: int = 4, length: int = 256):
+        """
+        Transform structures into array of integer features, where each feature is the count of its corresponding hash.
+        Each fragment (hash) contributes only one positional bit in the fingerprint.
+
+        :param min_radius: minimal radius of EC
+        :param max_radius: maximum radius of EC
+        :param length: fingerprint length. Should be power of 2
+        :return: array(n_features) of counts
+        """
+        mask = length - 1
+        fingerprint = zeros(length, dtype=int)
+        for hsh, cnt in self.morgan_hash_counts(min_radius, max_radius):
+            fingerprint[hsh & mask] += cnt
+        return fingerprint
+
+
+
     @property
     def _atom_identifiers(self) -> Dict[int, int]:
         raise NotImplementedError

diff --git a/chython/containers/reaction.py b/chython/containers/reaction.py
@@ -29,6 +29,7 @@
 from ..algorithms.depict import DepictReaction
 from ..algorithms.mapping import Mapping
 from ..algorithms.standardize import StandardizeReaction
+from numpy import zeros
 
 
 class ReactionContainer(StandardizeReaction, Mapping, Calculate2DReaction, DepictReaction):
@@ -321,4 +322,33 @@ def __len__(self):
         return len(self.reactants) + len(self.products) + len(self.reagents)
 
 
+    def diff_fingerprint(self, min_radius: int = 1, max_radius: int = 4, length: int = 1024, number_active_bits: int = 2, count_fp: bool = False):
+        """
+        Calculate the difference fingerprint for a reaction: products minus reactants.
+
+        :param reaction: ReactionContainer object
+        :param min_radius: minimal radius of EC
+        :param max_radius: maximum radius of EC
+        :param length: fingerprint length. Should be power of 2
+        :param number_active_bits: number of active bits for each hashed tuple (int or 'auto'). For 'auto' option, number of bits is count of each hash + 1.
+
+        :return: array(n_features) of difference counts
+        """
+        reactant_fp = zeros(length, dtype=uint8)
+        product_fp = zeros(length, dtype=uint8)
+
+        if count_fp:
+            for mol in self.reactants:
+                reactant_fp += mol.morgan_count_fingerprint(min_radius, max_radius, length)
+            for mol in self.products:
+                product_fp += mol.morgan_count_fingerprint(min_radius, max_radius, length)
+            r_fp = product_fp - reactant_fp
+        else:
+            for mol in self.reactants:
+                reactant_fp |= mol.morgan_fingerprint(min_radius, max_radius, length, number_active_bits)
+            for mol in self.products:
+                product_fp |= mol.morgan_fingerprint(min_radius, max_radius, length, number_active_bits)
+            r_fp = product_fp & ~reactant_fp
+        return r_fp
+
 __all__ = ['ReactionContainer']
diff --git a/chython/reactor/reactions/__init__.py b/chython/reactor/reactions/__init__.py
@@ -29,6 +29,13 @@
 from ._sonogashira import template as songashira_template
 from ._sulfonamidation import template as sulfonamidation_template
 from ._suzuki_miyaura import template as suzuki_miyaura_template
+from ._xec_sp2_sp3 import template as xec_sp2_sp3_template
+from ._aromatic_C_O import template as aromatic_C_O_template
+from ._aliphatic_C_O import template as aliphatic_C_O_template
+from ._aliphatic_C_N import template as aliphatic_C_N_template
+from ._mitsunobu import template as mitsunobu_template
+from ._decarboxylative_xec import template as decarboxylative_xec_template
+from ._negishi import template as negishi_template
 from ..reactor import Reactor, fix_mapping_overlap
 from ... import smarts, ReactionContainer, MoleculeContainer
 

diff --git a/chython/reactor/reactions/_aliphatic_C_N.py b/chython/reactor/reactions/_aliphatic_C_N.py
@@ -0,0 +1,50 @@
+# -*- coding: utf-8 -*-
+#
+#  Copyright 2022-2024 Ramil Nugmanov <[email protected]>
+#  Copyright 2023 Timur Gimadiev <[email protected]>
+#  This file is part of chython.
+#
+#  chython is free software; you can redistribute it and/or modify
+#  it under the terms of the GNU Lesser General Public License as published by
+#  the Free Software Foundation; either version 3 of the License, or
+#  (at your option) any later version.
+#
+#  This program is distributed in the hope that it will be useful,
+#  but WITHOUT ANY WARRANTY; without even the implied warranty of
+#  MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
+#  GNU Lesser General Public License for more details.
+#
+#  You should have received a copy of the GNU Lesser General Public License
+#  along with this program; if not, see <https://www.gnu.org/licenses/>.
+#
+
+
+template = {
+    'name': 'Aliphatic C-N coupling reaction',
+    'description': 'Nucleophilic substitution of aliphatic chlorides, bromides, iodides, sulfonates and sulfates with nitrogen nucleophiles such as amines, amides, hydrazines, hydrazones, N-H-aromatic heterocycles, etc.',
+    'templates': [
+        {
+            'A': [
+                # Hal-Alk
+                '[Cl,Br,I;D1:1]-[C;z1:2]',
+                # Alk-Sulfonate, i.e. mesylates, tosylates, triflates, nosylates, brosylates, etc.
+                '[C;z1:2]-[O:1]-[S;D4:4](=[O:5])(=[O:6])-[C:7]',
+                # Dimethyl sulfate, diethyl sulfate, etc.
+                '[C;z1:2]-[O:1]-[S;D4:4](=[O:5])(=[O:6])-[O:7]-[C:8]',
+            ],
+            'B': [
+                # Very generic nitrogen nucleophile, can be amine, amide, hydrazine, hydrazone, N-H-aromatic heterocycle, etc.
+                # The only requirement is that nitrogen has at least one hydrogen attached to it
+                '[N;h1,h2,h3:3]',
+                '[N:3]-[H:9]'
+            ],
+            'product': '[A:2]-[A:3]',
+            'alerts': [],
+            'ufe': {
+                'A': 1,
+                'B': '[A:3][At;M]'
+            }
+        }
+    ],
+    'alerts': []
+}
diff --git a/chython/reactor/reactions/_aliphatic_C_O.py b/chython/reactor/reactions/_aliphatic_C_O.py
@@ -0,0 +1,50 @@
+# -*- coding: utf-8 -*-
+#
+#  Copyright 2022-2024 Ramil Nugmanov <[email protected]>
+#  Copyright 2023 Timur Gimadiev <[email protected]>
+#  This file is part of chython.
+#
+#  chython is free software; you can redistribute it and/or modify
+#  it under the terms of the GNU Lesser General Public License as published by
+#  the Free Software Foundation; either version 3 of the License, or
+#  (at your option) any later version.
+#
+#  This program is distributed in the hope that it will be useful,
+#  but WITHOUT ANY WARRANTY; without even the implied warranty of
+#  MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
+#  GNU Lesser General Public License for more details.
+#
+#  You should have received a copy of the GNU Lesser General Public License
+#  along with this program; if not, see <https://www.gnu.org/licenses/>.
+#
+
+
+template = {
+    'name': 'Aliphatic C-O coupling reaction',
+    'description': 'Nucleophilic substitution of aliphatic chlorides, bromides, iodides, sulfonates and sulfates with alcohols and phenols.  Williamson ether synthesis or whatever is your preferred name for this type of reaction',
+    'templates': [
+        {
+            'A': [
+                # Hal-Alk
+                '[Cl,Br,I;D1:1]-[C;z1:2]',
+                # Alk-Sulfonate, i.e. mesylates, tosylates, triflates, nosylates, brosylates, etc.
+                '[C;z1:2]-[O:1]-[S;D4:4](=[O:5])(=[O:6])-[C:7]',
+                # Dimethyl sulfate, diethyl sulfate, etc.
+                '[C;z1:2]-[O:1]-[S;D4:4](=[O:5])(=[O:6])-[O:7]-[C:8]',
+            ],
+            'B': [
+                # Ar-OH
+                '[O;D1;x0;z1:3][C;a;M]',
+                # Alk-OH
+                '[O;D1;x0;z1:3][C;z1;x1;M]',
+            ],
+            'product': '[A:2]-[A:3]',
+            'alerts': [],
+            'ufe': {
+                'A': 1,
+                'B': '[A:3][At;M]'
+            }
+        }
+    ],
+    'alerts': []
+}
diff --git a/chython/reactor/reactions/_aromatic_C_O.py b/chython/reactor/reactions/_aromatic_C_O.py
@@ -0,0 +1,46 @@
+# -*- coding: utf-8 -*-
+#
+#  Copyright 2022-2024 Ramil Nugmanov <[email protected]>
+#  Copyright 2023 Timur Gimadiev <[email protected]>
+#  This file is part of chython.
+#
+#  chython is free software; you can redistribute it and/or modify
+#  it under the terms of the GNU Lesser General Public License as published by
+#  the Free Software Foundation; either version 3 of the License, or
+#  (at your option) any later version.
+#
+#  This program is distributed in the hope that it will be useful,
+#  but WITHOUT ANY WARRANTY; without even the implied warranty of
+#  MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
+#  GNU Lesser General Public License for more details.
+#
+#  You should have received a copy of the GNU Lesser General Public License
+#  along with this program; if not, see <https://www.gnu.org/licenses/>.
+#
+
+
+template = {
+    'name': 'Aromatic C-O coupling reaction',
+    'description': 'Aromatic C-O coupling reaction of aryl chlorides, bromides, and iodides with with alcohols and phenols',
+    'templates': [
+        {
+            'A': [
+                # Hal-Ar
+                '[Cl,Br,I;D1:1]-[C;a:2]'
+            ],
+            'B': [
+                # Ar-OH
+                '[O;D1;x0;z1:3][C;a;M]',
+                # Alk-OH
+                '[O;D1;x0;z1:3][C;z1;x1;M]',
+            ],
+            'product': '[A:2]-[A:3]',
+            'alerts': [],
+            'ufe': {
+                'A': 1,
+                'B': '[A:3][At;M]'
+            }
+        }
+    ],
+    'alerts': []
+}
diff --git a/chython/reactor/reactions/_buchwald_hartwig.py b/chython/reactor/reactions/_buchwald_hartwig.py
@@ -26,7 +26,9 @@
         {
             'A': [
                 # Hal-Ar
-                '[Cl,Br,I;D1:1]-[C;a:2]'
+                '[Cl,Br,I;D1:1]-[C;a:2]',
+                # Ar triflate
+                '[C;a:2]-[O;D2;x1:1]-[S;x3;D4:10](=[O:11])(=[O:12])-[C;D4;z1:13](-[F;D1:14])(-[F;D1:15])-[F;D1:16]'
             ],
             'B': [
                 # Ar-NH2

diff --git a/chython/reactor/reactions/_decarboxylative_xec.py b/chython/reactor/reactions/_decarboxylative_xec.py
@@ -0,0 +1,45 @@
+# -*- coding: utf-8 -*-
+#
+#  Copyright 2024 Ramil Nugmanov <[email protected]>
+#  This file is part of chython.
+#
+#  chython is free software; you can redistribute it and/or modify
+#  it under the terms of the GNU Lesser General Public License as published by
+#  the Free Software Foundation; either version 3 of the License, or
+#  (at your option) any later version.
+#
+#  This program is distributed in the hope that it will be useful,
+#  but WITHOUT ANY WARRANTY; without even the implied warranty of
+#  MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
+#  GNU Lesser General Public License for more details.
+#
+#  You should have received a copy of the GNU Lesser General Public License
+#  along with this program; if not, see <https://www.gnu.org/licenses/>.
+#
+
+
+template = {
+    'name': 'Macmillan',
+    'description': 'Deoxygenative C-C coupling reaction',
+    'templates': [
+        {
+            'A': [
+                # Hal-Ar
+                '[Cl,Br,I;D1:1]-[C;a:2]'
+            ],
+            'B': [
+                # AlkCOOH
+                '[C;z1:3]-[C;x2;z2:4](=[O:5])-[O;D1;x0;z1:6]',
+                # Redox ester
+                '[C;z1:3]-[C;x2;z2:4](=[O:5])-[O;D2;x1;z1:6]-[N;z1;x1;D3:7]1-[C;x2;z2:8](=[O:9])-[C;x0;z2,z4:10]!#[C;x0;z2,z4:11]-[C;x2;z2:12](=[O:13])-1'
+            ],
+            'product': '[A:2]-[A:3]',
+            'alerts': [],
+            'ufe': {
+                'A': 1,
+                'B': 3
+            }
+        }
+    ],
+    'alerts': []
+}