chython 2.19__cp313-cp313-win_amd64.whl

chython/algorithms/standardize/_isomers.py

@@ -0,0 +1,330 @@
+# -*- coding: utf-8 -*-
+#
+#  Copyright 2021-2026 Ramil Nugmanov <nougmanoff@protonmail.com>
+#  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/>.
+#
+from lazy_object_proxy import Proxy
+
+
+def _rules():
+    """
+    Rules for canonical positioning of charges and hydrogens.
+
+    Rule format: (query, rule_type)
+
+    rule_type:
+      'charge_fixed'         - deterministic charge move from atom_1 to atom_2
+      'charge_fixed_bridge'  - deterministic charge move from atom_3 (bridge) to atom_2
+      'charge_morgan'        - Morgan-dependent charge (atom_1 currently charged)
+      'charge_morgan_bridge' - Morgan-dependent charge (atom_3 bridge currently charged)
+      'ferrocene'            - ferrocene Cp ring charge
+      'tautomer_fixed'       - deterministic H move
+      'tautomer_morgan'      - Morgan-dependent H (atom_1 is donor)
+      'tautomer_morgan_donor' - Morgan-dependent H (atom_3 is donor)
+      'amidine'              - global H+bond resolution
+
+    Charge rules encode atom validity constraints in SMARTS:
+      - D2;h1: pyrrole-like NH+ (2 aromatic bonds + 1 implicit H)
+      - D3([A]): substituted N+ candidate with any single-bonded atom
+
+    Each charge rule has 4 variants for atom_1/atom_2 combinations:
+      HH: both D2;h1
+      HA: atom_1 D2;h1, atom_2 D3
+      AH: atom_1 D3, atom_2 D2;h1
+      AA: both D3
+    """
+    from ... import smarts
+
+    rules = []
+
+    # === charge_fixed: deterministic charge positioning ===
+    # These rules match fused 5+5 and 5+6 ring systems where the canonical charge position is known.
+    # charge_fixed: atom_1 is the current charge holder; charge moves to atom_2.
+    # charge_fixed_bridge: atom_3 (bridge N) is the current charge holder; charge moves to atom_2.
+
+    # --- Rule 1: N1C=CN2[NH+]=CC=C12 -> N1C=CC2=[NH+]C=CN12 ---
+    # HH variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[N;r5:3]:2:[C;r5](:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:2):[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # HA variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[N;r5:3]:2:[C;r5](:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:2):[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AH variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[N;r5:3]:2:[C;r5](:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:2):[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AA variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[N;r5:3]:2:[C;r5](:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:2):[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+
+    # --- Rule 2: N1C=C[N+]2=C1C=CN2 -> N1C=CC2=[NH+]C=CN12 ---
+    # atom_3 is the charged bridge N (unconstrained D - can be D3 all-aromatic)
+    # HH variant
+    q = smarts('[N;a;r5;+:3]:1:2:[N;r5;D2;h1:1]:[C;r5]:[C;r5]:[C;r5]:1:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+    # HA variant
+    q = smarts('[N;a;r5;+:3]:1:2:[N;r5;D2;h1:1]:[C;r5]:[C;r5]:[C;r5]:1:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+    # AH variant
+    q = smarts('[N;a;r5;+:3]:1:2:[N;r5;D3:1]([A]):[C;r5]:[C;r5]:[C;r5]:1:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+    # AA variant
+    q = smarts('[N;a;r5;+:3]:1:2:[N;r5;D3:1]([A]):[C;r5]:[C;r5]:[C;r5]:1:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+
+    # --- Rule 3: N1C=C2C=CN[N+]2=C1 -> N1C=CC2=C[NH+]=CN12 ---
+    # atom_3 is the charged bridge N (unconstrained D)
+    # HH variant
+    q = smarts('[N;a;r5;+:3]:1:2:[N;r5;D2;h1:1]:[C;r5]:[C;r5]:[C;r5]:1:[C;r5]:[N;r5;D2;h1:2]:[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+    # HA variant
+    q = smarts('[N;a;r5;+:3]:1:2:[N;r5;D2;h1:1]:[C;r5]:[C;r5]:[C;r5]:1:[C;r5]:[N;r5;D3:2]([A]):[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+    # AH variant
+    q = smarts('[N;a;r5;+:3]:1:2:[N;r5;D3:1]([A]):[C;r5]:[C;r5]:[C;r5]:1:[C;r5]:[N;r5;D2;h1:2]:[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+    # AA variant
+    q = smarts('[N;a;r5;+:3]:1:2:[N;r5;D3:1]([A]):[C;r5]:[C;r5]:[C;r5]:1:[C;r5]:[N;r5;D3:2]([A]):[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+
+    # --- Rule 4: N1C=C2NC=C[N+]2=C1 -> N1C=CN2C=[NH+]C=C12 ---
+    # atom_3 is the charged bridge N (unconstrained D)
+    # HH variant
+    q = smarts('[N;a;r5;+:3]:1:2:[C;r5](:[N;r5;D2;h1:1]:[C;r5]:[C;r5]:1):[C;r5]:[N;r5;D2;h1:2]:[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+    # HA variant
+    q = smarts('[N;a;r5;+:3]:1:2:[C;r5](:[N;r5;D2;h1:1]:[C;r5]:[C;r5]:1):[C;r5]:[N;r5;D3:2]([A]):[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+    # AH variant
+    q = smarts('[N;a;r5;+:3]:1:2:[C;r5](:[N;r5;D3:1]([A]):[C;r5]:[C;r5]:1):[C;r5]:[N;r5;D2;h1:2]:[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+    # AA variant
+    q = smarts('[N;a;r5;+:3]:1:2:[C;r5](:[N;r5;D3:1]([A]):[C;r5]:[C;r5]:1):[C;r5]:[N;r5;D3:2]([A]):[C;r5]:2')
+    rules.append((q, 'charge_fixed_bridge'))
+
+    # --- Rule 5: N1C2=[NH+]C=CC2=CC=C1 -> N1C=CC2=CC=C[NH+]=C12 ---
+    # HH variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r6]:2:[N;r6;D2;h1:2]:[C;r6]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # HA variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r6]:2:[N;r6;D3:2]([A]):[C;r6]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AH variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r6]:2:[N;r6;D2;h1:2]:[C;r6]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AA variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r6]:2:[N;r6;D3:2]([A]):[C;r6]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+
+    # --- Rule 6: N1C=C2C(=CC=[NH+]2)C=C1 -> N1C=CC2=CC=[NH+]C=C12 ---
+    # HH variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r6]:2:[C;r6]:[N;r6;D2;h1:2]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # HA variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r6]:2:[C;r6]:[N;r6;D3:2]([A]):[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AH variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r6]:2:[C;r6]:[N;r6;D2;h1:2]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AA variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r6]:2:[C;r6]:[N;r6;D3:2]([A]):[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+
+    # --- Rule 7: C1=CC=2C(=[NH+]1)C=CNC=2 -> N1C=CC2=C[NH+]=CC=C12 ---
+    # HH variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r6]:2:[C;r6]:[C;r6]:[N;r6;D2;h1:2]:[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # HA variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r6]:2:[C;r6]:[C;r6]:[N;r6;D3:2]([A]):[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AH variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r6]:2:[C;r6]:[C;r6]:[N;r6;D2;h1:2]:[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AA variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r6]:2:[C;r6]:[C;r6]:[N;r6;D3:2]([A]):[C;r6]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+
+    # --- Rule 8: C=1C=[NH+]C=2C=1NC=CC=2 -> N1C=CC2=[NH+]C=CC=C12 ---
+    # HH variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r6]:2:[C;r6]:[C;r6]:[C;r6]:[N;r6;D2;h1:2]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # HA variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r6]:2:[C;r6]:[C;r6]:[C;r6]:[N;r6;D3:2]([A]):[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AH variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r6]:2:[C;r6]:[C;r6]:[C;r6]:[N;r6;D2;h1:2]:[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AA variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r6]:2:[C;r6]:[C;r6]:[C;r6]:[N;r6;D3:2]([A]):[C;r5]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+
+    # --- Rule 9: C1=2C=[NH+]C=C1NC=CC=2 -> N1C=C2C=CC=[NH+]C2=C1 ---
+    # HH variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r5]:[C;r6]:2:[N;r6;D2;h1:2]:[C;r6]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # HA variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r5]:[C;r6]:2:[N;r6;D3:2]([A]):[C;r6]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AH variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r5]:[C;r6]:2:[N;r6;D2;h1:2]:[C;r6]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AA variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r5]:[C;r6]:2:[N;r6;D3:2]([A]):[C;r6]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+
+    # --- Rule 10: C1=2C=CNC=C1C=[NH+]C=2 -> N1C=C2C=C[NH+]=CC2=C1 ---
+    # HH variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r5]:[C;r6]:2:[C;r6]:[N;r6;D2;h1:2]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # HA variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r5]:[C;r6]:2:[C;r6]:[N;r6;D3:2]([A]):[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AH variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r5]:[C;r6]:2:[C;r6]:[N;r6;D2;h1:2]:[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+    # AA variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r5]:[C;r6]:2:[C;r6]:[N;r6;D3:2]([A]):[C;r6]:[C;r6]:[C;r5]:2:[C;r5]:1')
+    rules.append((q, 'charge_fixed'))
+
+    # === tautomer_fixed: deterministic H positioning ===
+
+    # 1,2,4-triazole: N1C=NC=N1 -> N1C=NN=C1
+    q = smarts('[N;a;r5;D2;h1;x1:2]:1:[N;r5;D2;h0;x1]:[C;r5]:[N;r5;D2;h0;x0:1]:[C;r5]:1')
+    rules.append((q, 'tautomer_fixed'))
+
+    # tetrazole: N1N=CN=N1 -> N1C=NN=N1
+    q = smarts('[N;a;r5;D2;h0;x1:1]:1:[N;r5;D2;h1;x2:2]:[N;r5;D2;h0;x2]:[N;r5;D2;h0;x1]:[C;r5]:1')
+    rules.append((q, 'tautomer_fixed'))
+
+    # === charge_morgan: Morgan-dependent charge positioning ===
+    # Morgan ordering decides which atom gets the charge.
+
+    # --- Rule M1: indazole+ fused (5+5 ring, N-N bridge) ---
+    # HH variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[N;D3]:2:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:[C;D3]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # HA variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[N;D3]:2:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:[C;D3]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # AH variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[N;D3]:2:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:[C;D3]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # AA variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[N;D3]:2:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:[C;D3]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+
+    # --- Rule M2: indazole+ fused (bridge variant, charge on bridge N) ---
+    # HH variant for atom_1/atom_2
+    q = smarts('[N;a;D3;r5;+:3]:1:2:[N;r5;D2;h1:1]:[C;r5]:[C;r5]:[C;D3]:1:[C;r5]:[C;r5]:[N;r5;D2;h1:2]:2')
+    rules.append((q, 'charge_morgan_bridge'))
+    # HA variant
+    q = smarts('[N;a;D3;r5;+:3]:1:2:[N;r5;D2;h1:1]:[C;r5]:[C;r5]:[C;D3]:1:[C;r5]:[C;r5]:[N;r5;D3:2]([A]):2')
+    rules.append((q, 'charge_morgan_bridge'))
+    # AH variant
+    q = smarts('[N;a;D3;r5;+:3]:1:2:[N;r5;D3:1]([A]):[C;r5]:[C;r5]:[C;D3]:1:[C;r5]:[C;r5]:[N;r5;D2;h1:2]:2')
+    rules.append((q, 'charge_morgan_bridge'))
+    # AA variant
+    q = smarts('[N;a;D3;r5;+:3]:1:2:[N;r5;D3:1]([A]):[C;r5]:[C;r5]:[C;D3]:1:[C;r5]:[C;r5]:[N;r5;D3:2]([A]):2')
+    rules.append((q, 'charge_morgan_bridge'))
+
+    # --- Rule M3: imidazole fused (5+5, C-N-C bridge) ---
+    # HH variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;D3]:2:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:[N;D3]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # HA variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;D3]:2:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:[N;D3]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # AH variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;D3]:2:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:[N;D3]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # AA variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;D3]:2:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:[N;D3]:2:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+
+    # --- Rule M4: imidazole fused (bridge variant, charge on bridge) ---
+    # HH variant
+    q = smarts('[N;a;D3;r5;+:3]:1:2:[C;D3](:[N;r5;D2;h1:1]:[C;r5]:[C;r5]:1):[N;r5;D2;h1:2]:[C;r5]:[C;r5]:2')
+    rules.append((q, 'charge_morgan_bridge'))
+    # HA variant
+    q = smarts('[N;a;D3;r5;+:3]:1:2:[C;D3](:[N;r5;D2;h1:1]:[C;r5]:[C;r5]:1):[N;r5;D3:2]([A]):[C;r5]:[C;r5]:2')
+    rules.append((q, 'charge_morgan_bridge'))
+    # AH variant
+    q = smarts('[N;a;D3;r5;+:3]:1:2:[C;D3](:[N;r5;D3:1]([A]):[C;r5]:[C;r5]:1):[N;r5;D2;h1:2]:[C;r5]:[C;r5]:2')
+    rules.append((q, 'charge_morgan_bridge'))
+    # AA variant
+    q = smarts('[N;a;D3;r5;+:3]:1:2:[C;D3](:[N;r5;D3:1]([A]):[C;r5]:[C;r5]:1):[N;r5;D3:2]([A]):[C;r5]:[C;r5]:2')
+    rules.append((q, 'charge_morgan_bridge'))
+
+    # --- Rule M5: imidazolium (simple 5-ring) ---
+    # HH variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r5]:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # HA variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[C;r5]:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # AH variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r5]:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # AA variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[C;r5]:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+
+    # --- Rule M6: pyrazolium (simple 5-ring) ---
+    # HH variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # HA variant
+    q = smarts('[N;a;r5;D2;h1;+:1]:1:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # AH variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[N;r5;D2;h1:2]:[C;r5]:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+    # AA variant
+    q = smarts('[N;a;r5;D3;+:1]([A]):1:[N;r5;D3:2]([A]):[C;r5]:[C;r5]:[C;r5]:1')
+    rules.append((q, 'charge_morgan'))
+
+    # === ferrocene ===
+    q = smarts('[C;a;r5;-:1]:1:[C;a;r5:2]:[C;a;r5:3]:[C;a;r5:4]:[C;a;r5:5]:1')
+    rules.append((q, 'ferrocene'))
+
+    # === tautomer_morgan: Morgan-dependent H positioning ===
+
+    # pyrazole
+    q = smarts('[N;a;r5;D2;h1;x1:1]:1:[N;r5;D2;h0;x1:2]:[C;r5]:[C;r5]:[C;r5]:1')
+    rules.append((q, 'tautomer_morgan'))
+
+    # imidazole
+    q = smarts('[N;a;r5;D2;h1;x0:1]:1:[C;r5]:[N;r5;D2;h0;x0:2]:[C;r5]:[C;r5]:1')
+    rules.append((q, 'tautomer_morgan'))
+
+    # 1,2,3-triazole
+    q = smarts('[N;a;r5;D2;h1;x1:1]:1:[N;r5;D2;h0;x2]:[N;r5;D2;h0;x1:2]:[C;r5]:[C;r5]:1')
+    rules.append((q, 'tautomer_morgan'))
+
+    # 1,2,3-triazole (donor variant)
+    q = smarts('[N;a;r5;D2;h0;x1:1]:1:[N;r5;D2;h1;x2:3]:[N;r5;D2;h0;x1:2]:[C;r5]:[C;r5]:1')
+    rules.append((q, 'tautomer_morgan_donor'))
+
+    # === amidine: global H+bond resolution ===
+    q = smarts('[N;h0,h1;z2:1]=[C;z2;x2,x3;!R:3]-[N;h1,h2;z1:2]')
+    rules.append((q, 'amidine'))
+
+    return rules
+
+
+rules = Proxy(_rules)
+
+
+__all__ = ['rules']

chython/algorithms/standardize/_metal_organics.py

@@ -0,0 +1,189 @@
+# -*- coding: utf-8 -*-
+#
+#  Copyright 2021-2026 Ramil Nugmanov <nougmanoff@protonmail.com>
+#  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/>.
+#
+from lazy_object_proxy import Proxy
+
+
+def _rules():
+    from ... import smarts
+
+    rules = []
+
+    #
+    #        R - N - C                 R - N - C
+    #           /    ||                   /    ||
+    #  A - M = C     || >>    A - M .. [C-]    ||
+    #           \    ||                  \\    ||
+    #        R - N - C               R - [N+]- C
+    #
+    q = smarts('[M:1]=[C:2]-1-[N;D3;x0;z1:3]-[C;z2:5]-,=[C;z2:6]-[N;D3;x0;z1:4]-1')
+    atom_fix = {2: (-1, None), 3: (1, None)}  # atom: (charge diff, new radical state or None)
+    bonds_fix = ((1, 2, 8), (2, 3, 2))
+    rules.append((q, atom_fix, bonds_fix))
+
+    #
+    # cyanide
+    #
+    q = smarts('[M:3]-[C:1]#[N:2]')
+    # NOTE: first fixed atom is metal. required for preventing errors in charge.
+    # based on ordered dict nature.
+    atom_fix = {3: (1, None), 1: (-1, None)}
+    bonds_fix = ((1, 3, 8),)
+    rules.append((q, atom_fix, bonds_fix))
+
+    q = smarts('[M:3]-[C-:1]#[N:2]')
+    atom_fix = {}
+    bonds_fix = ((1, 3, 8),)
+    rules.append((q, atom_fix, bonds_fix))
+
+    #
+    # cyanate/fulminate
+    #
+    q = smarts('[M:1]-[O,S;D2:2]-[C:3]#[N:4]')
+    atom_fix = {1: (1, None), 4: (-1, None)}
+    bonds_fix = ((1, 2, 8), (2, 3, 2), (3, 4, 2))
+    rules.append((q, atom_fix, bonds_fix))
+
+    q = smarts('[M:1]-[N:2]=[C:3]=[O,S;D1:4]')
+    atom_fix = {1: (1, None), 2: (-1, None)}
+    bonds_fix = ((1, 2, 8),)
+    rules.append((q, atom_fix, bonds_fix))
+
+    q = smarts('[M:1]-[O,S;D2:2]-[N+:3]#[C-:4]')
+    atom_fix = {1: (1, None), 2: (-1, None)}
+    bonds_fix = ((1, 2, 8),)
+    rules.append((q, atom_fix, bonds_fix))
+
+    q = smarts('[M:1]-[C:2]#[N+:3]-[O,S;D1-:4]')
+    atom_fix = {1: (1, None), 2: (-1, None)}
+    bonds_fix = ((1, 2, 8),)
+    rules.append((q, atom_fix, bonds_fix))
+
+    #
+    # carbonyl
+    #
+    q = smarts('[M:3]-[C:1]#[O:2]')
+    atom_fix = {1: (-1, None), 2: (1, None)}
+    bonds_fix = ((1, 3, 8),)
+    rules.append((q, atom_fix, bonds_fix))
+
+    q = smarts('[M:3]-[C:1]=[O:2] |^1:1|')
+    atom_fix = {1: (-1, False), 2: (1, None)}
+    bonds_fix = ((1, 3, 8), (1, 2, 3))
+    rules.append((q, atom_fix, bonds_fix))
+
+    q = smarts('[M:3]-[C;D2:1]=[O:2]')
+    atom_fix = {1: (-1, None), 2: (1, None)}
+    bonds_fix = ((1, 3, 8), (1, 2, 3))
+    rules.append((q, atom_fix, bonds_fix))
+
+    q = smarts('[M:3]-[C:1](-[M:4])=[O:2]')
+    atom_fix = {1: (-1, None), 2: (1, None)}
+    bonds_fix = ((1, 3, 8), (1, 4, 8), (1, 2, 3))
+    rules.append((q, atom_fix, bonds_fix))
+
+    #
+    # Ferrocene covalent uncharged
+    #
+    q = smarts('[M:1]-1-2-3-4-[C:2]-5-[C:3]-1-[C:4]-2-[C:5]-3-[C:6]-4-5')
+    atom_fix = {1: (1, None), 2: (-1, None)}
+    bonds_fix = ((1, 2, 8), (1, 3, 8), (1, 4, 8), (1, 5, 8), (1, 6, 8), (3, 4, 2), (5, 6, 2))
+    rules.append((q, atom_fix, bonds_fix))
+
+    #
+    # Ferrocene covalent uncharged. invalid valence.
+    #
+    q = smarts('[M:1]-1-2-3-4-[C:2]-5-[C:3]-1=[C:4]-2-[C:5]-3=[C:6]-4-5')
+    atom_fix = {1: (1, None), 2: (-1, None)}
+    bonds_fix = ((1, 2, 8), (1, 3, 8), (1, 4, 8), (1, 5, 8), (1, 6, 8), (3, 4, 2), (5, 6, 2))
+    rules.append((q, atom_fix, bonds_fix))
+
+    #
+    # Ferrocene covalent radical carbon
+    #
+    q = smarts('[M:1]-1-2-3-4-[C:2]-5-[C:3]-1=[C:4]-2-[C:5]-3=[C:6]-4-5 |^1:1|')
+    atom_fix = {1: (1, None), 2: (-1, False), 3: (0, False), 4: (0, False), 5: (0, False), 6: (0, False)}
+    bonds_fix = ((1, 2, 8), (1, 3, 8), (1, 4, 8), (1, 5, 8), (1, 6, 8), (3, 4, 2), (5, 6, 2))
+    rules.append((q, atom_fix, bonds_fix))
+
+    #
+    # Ferrocene covalent charged
+    #
+    q = smarts('[M:1]-1-2-3-4-[C-:2]-5-[C:3]-1=[C:4]-2-[C:5]-3=[C:6]-4-5')
+    atom_fix = {}
+    bonds_fix = ((1, 2, 8), (1, 3, 8), (1, 4, 8), (1, 5, 8), (1, 6, 8))
+    rules.append((q, atom_fix, bonds_fix))
+
+    #
+    # Ferrocene coordinate radical carbon
+    #
+    q = smarts('[M:1]~1~2~3~4~[C:2]-5-[C:3]~1=[C:4]~2-[C:5]~3=[C:6]~4-5 |^1:1|')
+    atom_fix = {1: (1, None), 2: (-1, False), 3: (0, False), 4: (0, False), 5: (0, False), 6: (0, False)}
+    bonds_fix = ((3, 4, 2), (5, 6, 2))
+    rules.append((q, atom_fix, bonds_fix))
+
+    #
+    # Allyl complexes
+    #
+    q = smarts('[M:1]~1~2~[C;z2:2]=[C:3]~1-[C:4]~2 |^1:3|')
+    atom_fix = {1: (1, None), 4: (-1, False)}
+    bonds_fix = ()
+    rules.append((q, atom_fix, bonds_fix))
+
+    #
+    # Phosphines
+    #
+    q = smarts('[M:1]-[P;D4;z1;+:2]-C')
+    atom_fix = {1: (1, None), 2: (-1, None)}
+    bonds_fix = ((1, 2, 8),)
+    rules.append((q, atom_fix, bonds_fix))
+
+    q = smarts('[M:1]-[P;D4;z1:2]-C')
+    atom_fix = {}
+    bonds_fix = ((1, 2, 8),)
+    rules.append((q, atom_fix, bonds_fix))
+
+    # Amines
+    q = smarts('[M:1]-[N;z1;+:2]-C')
+    atom_fix = {1: (1, None), 2: (-1, None)}
+    bonds_fix = ((1, 2, 8),)
+    rules.append((q, atom_fix, bonds_fix))
+
+    q = smarts('[M:1]-[N;z1:2]-C')
+    atom_fix = {}
+    bonds_fix = ((1, 2, 8),)
+    rules.append((q, atom_fix, bonds_fix))
+
+    # ethers
+    q = smarts('[M:1]-[O;D3;+:2](-C)-C')
+    atom_fix = {1: (1, None), 2: (-1, None)}
+    bonds_fix = ((1, 2, 8),)
+    rules.append((q, atom_fix, bonds_fix))
+
+    compiled_rules = []
+    for q, atom_fix, bonds_fix in rules:
+        any_atoms = [n for n, a in q.atoms() if a.atomic_symbol == 'A' and n not in atom_fix]
+        any_atoms.extend(n for n, a in q.atoms() if a.atomic_symbol == 'M')
+        compiled_rules.append((q, atom_fix, bonds_fix, any_atoms, False))
+    return compiled_rules
+
+
+rules = Proxy(_rules)
+
+
+__all__ = ['rules']

chython/algorithms/standardize/_reagents.py

@@ -0,0 +1,44 @@
+# -*- coding: utf-8 -*-
+#
+#  Copyright 2022-2026 Ramil Nugmanov <nougmanoff@protonmail.com>
+#  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/>.
+#
+from lazy_object_proxy import Proxy
+
+
+def _reagents():
+    from ... import smiles
+
+    tmp = ['N', 'O', 'F', 'Cl', 'Br', 'I', 'O=C=O',  # inorganic
+           'C1=CC=CC=C1', 'C1CCCCC1', 'CC1=CC=CC=C1', 'CCCCCC', 'CCCCCCC',  # hydrocarbon
+           'CO', 'CCO', 'CC(C)O',  # alcohol
+           'OC=O', 'CC(=O)O',  # acid
+           'CC(=O)OCC',  # ester
+           'CCOCC', 'C1COCC1',  # ether
+           ]
+
+    rules = set()
+    for x in tmp:
+        x = smiles(x)
+        x.thiele()
+        rules.add(x)
+    return rules
+
+
+reagents_set = Proxy(_reagents)
+
+
+__all__ = ['reagents_set']

chython/algorithms/standardize/_salts.py

@@ -0,0 +1,68 @@
+# -*- coding: utf-8 -*-
+#
+#  Copyright 2022-2026 Ramil Nugmanov <nougmanoff@protonmail.com>
+#  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/>.
+#
+from lazy_object_proxy import Proxy
+
+
+def _rules():
+    from ... import smarts
+    rules = []
+
+    # Oxo-acid salts
+    q = smarts('[O,S,Se;D2;z1:1]-[C,N,P,S,Cl,Se,Br,I,Si]=O')
+    rules.append(q)
+
+    # Thiophosphate salts
+    q = smarts('[O,S,Se;D2;z1:1]-[P]=[S,Se]')
+    rules.append(q)
+
+    # Phenole salts
+    q = smarts('[O,S,Se;D2;z1:1]-[C,N;a]')
+    rules.append(q)
+
+    # Nitrate
+    q = smarts('[O;D2;z1:1]-[N+](-[O-])=O')
+    rules.append(q)
+
+    # halogenides and hydroxy
+    q = smarts('[O,F,Cl,Br,I;D1;z1:1]')
+    rules.append(q)
+    return rules
+
+
+def _acids():
+    from ... import smiles
+
+    tmp = ['Cl', 'Br', 'I', 'O[N+](=O)[O-]', 'ON=O', 'OP(O)(O)=O', 'COP(O)(=O)OC',
+           'OS(O)(=O)=O', 'CS(O)(=O)=O', 'OS(=O)(=O)C(F)(F)F', 'CC1=CC=C(C=C1)S(O)(=O)=O',
+           'OC(O)=O', 'CC(O)=O', 'OC(=O)C(F)(F)F', 'OCC(O)=O', 'CC(O)C(O)=O', 'OC(=O)C(O)=O', 'OC(=O)C(Cl)Cl',
+           'OC(=O)C=CC(O)=O', 'OC(C(O)C(O)=O)C(O)=O',
+           'O[Cl](=O)(=O)=O']
+    acs = set()
+    for x in tmp:
+        x = smiles(x)
+        x.thiele()
+        acs.add(x)
+    return acs
+
+
+acids = Proxy(_acids)
+rules = Proxy(_rules)
+
+
+__all__ = ['acids', 'rules']