Implementation of atropisomer recognition & encoding

INCHI-1-SRC/INCHI_API/libinchi/src/CMakeLists.txt

@@ -54,6 +54,8 @@ target_sources(libinchi PRIVATE
 	${P_IXA}/ixa_read_mol.c
 	${P_IXA}/ixa_status.c
 	${P_IXA}/ixa_status.h
+	${P_BASE}/atropisomers.h
+	${P_BASE}/atropisomers.c
 	${P_BASE}/bcf_s.h
 	${P_BASE}/bcf_s.c
 	${P_BASE}/extr_ct.h
@@ -127,6 +129,8 @@ target_sources(libinchi PRIVATE
 	${P_BASE}/permutation_util.c
 	${P_BASE}/readinch.c
 	${P_BASE}/readinch.h
+	${P_BASE}/ring_detection.c
+	${P_BASE}/ring_detection.h
 	${P_BASE}/runichi.c
 	${P_BASE}/runichi2.c
 	${P_BASE}/runichi3.c

INCHI-1-SRC/INCHI_BASE/src/atropisomers.c

@@ -0,0 +1,132 @@
+
+
+#include "inpdef.h"
+#include "ring_detection.h"
+
+
+void find_atropisomeric_atoms_and_bonds(inp_ATOM* out_at,
+                                        int num_atoms,
+                                        RingSystems *ring_result,
+                                        ORIG_ATOM_DATA *orig_inp_data,
+                                        int *fused_atom_partner) {
+
+
+    printf("-------------------\n");
+
+    for (int i = 0; i < num_atoms; i++) {
+
+        int atom_id1 = i;
+        const inp_ATOM atom_i = out_at[atom_id1];
+
+        int num_neighbors_i = atom_i.valence;
+
+        const AT_NUMB *neighbors = atom_i.neighbor;
+
+        if (num_neighbors_i == 3) {
+            for (int j = 0; j < num_neighbors_i; j++) {
+
+                int atom_id2 = neighbors[j];
+
+                if (atom_id1 >= atom_id2) {
+                    continue;
+                }
+
+                const inp_ATOM atom_j = out_at[atom_id2];
+
+
+
+                int num_neighbors_j = atom_j.valence;
+
+                if (num_neighbors_j == 3 &&
+                    atom_i.bond_stereo[j] == 0 &&
+                    atom_i.bond_type[j] == 1) {
+
+                    if (ring_result->atom_to_ring_mapping[atom_id1].ring_count > 0 ||
+                        ring_result->atom_to_ring_mapping[atom_id2].ring_count > 0) {
+
+                        int nof_wedge_bonds_i = 0;
+                        int has_double_bond_i = 0;
+                        for (int k = 0; k < num_neighbors_i; k++) {
+                            if (atom_i.bond_stereo[k] == 1 ||
+                                atom_i.bond_stereo[k] == 4 ||
+                                atom_i.bond_stereo[k] == 6) {
+                                nof_wedge_bonds_i++;
+                            }
+                            if (atom_i.bond_type[k] == 2) {
+                                has_double_bond_i = 1;
+                            }
+                        }
+                        int nof_wedge_bonds_j = 0;
+                        int has_double_bond_j = 0;
+                        for (int k = 0; k < num_neighbors_j; k++) {
+                            if (atom_j.bond_stereo[k] == 1 ||
+                                atom_j.bond_stereo[k] == 4 ||
+                                atom_j.bond_stereo[k] == 6) {
+                                nof_wedge_bonds_j++;
+                            }
+                            if (atom_j.bond_type[k] == 2) {
+                                has_double_bond_j = 1;
+                            }
+                        }
+
+                        if (nof_wedge_bonds_i > 0 ||
+                            nof_wedge_bonds_j > 0) {
+
+                            if ((has_double_bond_i || has_double_bond_j)) {
+                                if ((fused_atom_partner[atom_id1] != j &&
+                                     fused_atom_partner[atom_id2] != i) ||
+                                    (fused_atom_partner[atom_id1] == -1 ||
+                                     fused_atom_partner[atom_id2] == -1)) {
+
+                                    if (are_atoms_in_same_small_ring(out_at,
+                                                                     ring_result,
+                                                                     atom_id1, atom_id2,
+                                                                     6) == 0) {
+                                        printf(">>> is atropisomer\n");
+                                        printf("infos: atom %d with atom %d; bond type %d; bond stereo %d\n",
+                                                atom_id1, atom_id2, atom_i.bond_type[j], atom_i.bond_stereo[j]);
+                                        // printf("atom type %d %d\n", atom_i.el_number, atom_j.el_number);
+                                        // printf("has double bond %d %d\n", has_double_bond_i, has_double_bond_j);
+                                        // printf("fused pivot atoms %d %d\n", fused_atom_partner[atom_id1], fused_atom_partner[atom_id2]);
+
+                                        //TODO set atoms with atropisomeric bonds in out_at
+                                        orig_inp_data->is_atropisomer = 1;
+                                    }
+                                }
+                            }
+                        }
+                    }
+                }
+            }
+        }
+    }
+
+    for (int i = 0; i < ring_result->count; i++) {
+        const Ring *cur_ring = &ring_result->rings[i];
+        if (cur_ring->size >= 8) {
+            int count_single_bonds = 0;
+            int count_double_bonds = 0;
+            for (int j = 0; j < cur_ring->size; j++) {
+                int atom_id1 = cur_ring->atom_ids[j];
+                int atom_id2 = cur_ring->atom_ids[(j + 1) % cur_ring->size];
+                const inp_ATOM atom1 = out_at[atom_id1];
+                for (int k = 0; k < atom1.valence; k++) {
+                    if (atom1.neighbor[k] == atom_id2) {
+                        if (atom1.bond_type[k] == 1) {
+                            count_single_bonds++;
+                        } else if (atom1.bond_type[k] == 2) {
+                            count_double_bonds++;
+                        }
+                    }
+                }
+            }
+
+            if (cur_ring->is_fused_ring == 0) {
+                printf(">>> ring id %d size %d nof single bonds %d nof double bonds %d fused ring %d\n",
+                    cur_ring->id, cur_ring->size,
+                    count_single_bonds, count_double_bonds,
+                    cur_ring->is_fused_ring);
+            }
+        }
+    }
+}

INCHI-1-SRC/INCHI_BASE/src/atropisomers.h

@@ -0,0 +1,9 @@
+
+#include "inpdef.h"
+#include "ring_detection.h"
+
+void find_atropisomeric_atoms_and_bonds(inp_ATOM* out_at,
+                                        int num_atoms,
+                                        RingSystems *ring_result,
+                                        ORIG_ATOM_DATA *orig_inp_data,
+                                        int *fused_atom_partner);

INCHI-1-SRC/INCHI_BASE/src/ichidrp.h

@@ -189,7 +189,8 @@ typedef struct tagInputParms {
     int             bMolecularInorganics;       /* (@nnuk : Nauman Ullah Khan) :: Varaible for Molecular Inorganics parameter */
     int             bMolecularInorganicsReconnectedInChI;  /* (@nnuk : Nauman Ullah Khan) :: Custom flag to indicate reconnected InChI requirement */
 
-    int             bEnhancedStereo;
+    int             bEnhancedStereo;        /* v. 1.0?+ enable enhanced stereochemistry                             */
+    int             Atropisomers;           /* v. 1.0?+ enable atropisomeric stereochemistry                        */
 
     /* */
     INCHI_MODE      bTautFlags;

INCHI-1-SRC/INCHI_BASE/src/ichimake.c

@@ -54,6 +54,9 @@
 
 #include "bcf_s.h"
 
+#include "atropisomers.h"
+#include "ring_detection.h"
+
 /*
     Local functions
 */
@@ -3901,6 +3904,38 @@ int  Create_INChI(CANON_GLOBALS* pCG,
     /*fix_odd_things( num_atoms, out_at );*/
 #if ( FIND_RING_SYSTEMS == 1 )
     MarkRingSystemsInp(out_at, num_atoms, 0);
+
+    orig_inp_data->is_atropisomer = 0;
+    if (ip->Atropisomers) {
+        RingSystems *ring_result = find_rings(out_at, num_atoms);
+
+        // print_ring_result(ring_result);
+        int fused_atom_partner[num_atoms];
+        for (i = 0; i < num_atoms; i++) {
+            // out_at[i].fused_partner_atom_id = -1;
+            fused_atom_partner[i] = -1;
+        }
+        for (i = 0; i < num_atoms; i++) {
+            for (int j = i + 1; j < num_atoms; j++) {
+                if(is_fused_ring_pivot(ring_result, out_at, i, j)) {
+                    fused_atom_partner[i] = j;
+                    fused_atom_partner[j] = i;
+                }
+            }
+        }
+
+        find_atropisomeric_atoms_and_bonds(out_at, num_atoms, ring_result, orig_inp_data, fused_atom_partner);
+
+        //map values to orig_inp_data
+        if (orig_inp_data->is_atropisomer) {
+            for (i = 0; i < num_atoms; i++) {
+                //todo set atoms with atropisomeric bonds in orig_atom_data
+            }
+        }
+
+        free_ring_system(ring_result);
+    }
+
 #endif
     /*  duplicate the preprocessed structure so that all supplied out_norm_data[]->at buffers are filled */
     if (out_at != out_norm_data[TAUT_YES]->at && out_norm_data[TAUT_YES]->at)

INCHI-1-SRC/INCHI_BASE/src/ichiparm.c

@@ -124,7 +124,8 @@ int set_common_options_by_parg(const char* pArg,
     int* pbMergeHash,
     int* pbHideInChI,
     int* pbMolecularInorganics,     /* @nnuk */
-    int* pbEnhancedStereochemistry);
+    int* pbEnhancedStereochemistry,
+    int* pbAtropisomers);
 
 
 /****************************************************************************
@@ -169,7 +170,8 @@ int set_common_options_by_parg(const char* pArg,
     int* pbMergeHash,
     int* pbHideInChI,
     int* pbMolecularInorganics,     /*@nnuk*/
-    int* pbEnhancedStereochemistry
+    int* pbEnhancedStereochemistry,
+    int* pbAtropisomers
 )
 {
     int got = 0;
@@ -275,6 +277,11 @@ int set_common_options_by_parg(const char* pArg,
         *pbEnhancedStereochemistry = 1;
         got = 1;
     }
+    else if (!inchi_stricmp(pArg, "Atropisomers"))
+    {
+        *pbAtropisomers = 1;
+        got = 1;
+    }
 
 #ifndef USE_STDINCHI_API
     /* These options DO TURN OFF Std flag   */
@@ -664,6 +671,7 @@ int ReadCommandLineParms(int argc,
     int bUnchargedAcidTaut = (CHARGED_SALTS_ONLY == 0);
     int bMergeSaltTGroups = (DISCONNECT_SALTS == 1);
     int bEnhancedStereochemistry = 0;
+    int bAtropisomers = 0;
 #if ( MIN_SB_RING_SIZE > 0 )
     int nMinDbRinSize = MIN_SB_RING_SIZE, mdbr = 0;
 #endif
@@ -816,7 +824,7 @@ int ReadCommandLineParms(int argc,
                 &bLargeMolecules, &bPolymers,
                 &bFoldPolymerSRU, &bFrameShiftScheme,
                 &bStereoAtZz, &bNPZz,
-                &bNoWarnings, &bMergeHash, &bHideInChI, &bMolecularInorganics, &bEnhancedStereochemistry);
+                &bNoWarnings, &bMergeHash, &bHideInChI, &bMolecularInorganics, &bEnhancedStereochemistry, &bAtropisomers);
             if (got)
             {
                 ;
@@ -1264,7 +1272,7 @@ int ReadCommandLineParms(int argc,
                 &bLargeMolecules, &bPolymers,
                 &bFoldPolymerSRU, &bFrameShiftScheme,
                 &bStereoAtZz, &bNPZz,
-                &bNoWarnings, &bMergeHash, &bHideInChI, &bMolecularInorganics, &bEnhancedStereochemistry);
+                &bNoWarnings, &bMergeHash, &bHideInChI, &bMolecularInorganics, &bEnhancedStereochemistry, &bAtropisomers);
 
             if ( got )
             {
@@ -2143,6 +2151,8 @@ int ReadCommandLineParms(int argc,
 
     ip->bEnhancedStereo = bEnhancedStereochemistry;
 
+    ip->Atropisomers = bAtropisomers;
+
     return 0;
 }
 

INCHI-1-SRC/INCHI_BASE/src/ichiprt1.c

@@ -1623,6 +1623,11 @@ int OutputINChI1( CANON_GLOBALS *pCG,
                 {
                     set_EnhancedStereo_t_m_layers(orig_inp_data, pINChI, pINChI_Aux);
                 }
+
+                if (ip->Atropisomers)
+                {
+                    set_Atropisomer_t_m_layers(orig_inp_data, pINChI, pINChI_Aux);
+                }
             }
         }
         if (bCompExists)
@@ -1714,6 +1719,10 @@ int OutputINChI1( CANON_GLOBALS *pCG,
         {
             is_beta = 1;
         }
+        else if (ip->Atropisomers)
+        {
+            is_beta = 1;
+        }
 
         OutputINCHI_VersionAndKind(out_file, strbuf, bINChIOutputOptions, is_beta, pLF, pTAB);
     }

INCHI-1-SRC/INCHI_BASE/src/inpdef.h

@@ -459,7 +459,9 @@ typedef struct tagOrigAtom
     OAD_Polymer *polymer;
     OAD_V3000 *v3000;
     int valid_polymer;
-    int n_zy; /* number of non-polymeric pseudoatoms (Zy)             */
+    int n_zy;               /* number of non-polymeric pseudoatoms (Zy)             */
+
+    int is_atropisomer;     /* flag indicating whether the structure is an atropisomer; it is set to 1 if the structure has been identified as an atropisomer during input processing, and 0 otherwise */
 
 } ORIG_ATOM_DATA;