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Improve reagent filter: known-solvent dictionary + catalyst metal detection
Three-tier reagent/solvent classification: 1. Known SMILES dictionary (40+ solvents, salts, reducing agents) 2. Catalyst metal detection (Pd, Pt, Rh, Ru, Cu, etc.) 3. Tanimoto fingerprint similarity (threshold raised to 0.4) 156 tests pass, no regressions. Co-Authored-By: Syed Asad Rahman <asad.rahman@bioinceptionlabs.com>
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Lines changed: 119 additions & 35 deletions

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‎src/main/java/com/bioinceptionlabs/reactionblast/tools/StandardizeReaction.java‎

Lines changed: 119 additions & 35 deletions
Original file line numberDiff line numberDiff line change
@@ -50,6 +50,65 @@ public class StandardizeReaction {
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private static final ILoggingTool LOGGER = createLoggingTool(StandardizeReaction.class);
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53+
/**
54+
* Common solvents, reagents, and catalysts by canonical SMILES.
55+
* These molecules never participate in bond-changing reactions —
56+
* they facilitate or mediate but their bonds don't change.
57+
*/
58+
private static final Set<String> KNOWN_REAGENT_SMILES = new HashSet<>(Arrays.asList(
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// Solvents
60+
"ClCCl", // DCM (dichloromethane)
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"ClC(Cl)Cl", // chloroform
62+
"CC(C)=O", // acetone
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"CCCCCC", // hexane
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"c1ccncc1", // pyridine (also base)
65+
"CC#N", // acetonitrile (MeCN)
66+
"CS(C)=O", // DMSO
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"CN(C)C=O", // DMF
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"C1CCOC1", // THF
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"CCOCC", // diethyl ether
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"C1COCCO1", // 1,4-dioxane
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"CO", // methanol
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"CCO", // ethanol
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"CC(C)O", // isopropanol
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"O", // water
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"CC(=O)O", // acetic acid (when used as solvent)
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"CCOC(C)=O", // ethyl acetate
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"c1ccccc1", // benzene
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"Cc1ccccc1", // toluene
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"c1ccc(cc1)C", // toluene alternate
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// Reducing agents
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"[Na+]", // sodium cation
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"[K+]", // potassium cation
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"[Li+]", // lithium cation
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"[Cs+]", // cesium cation
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"[NH4+]", // ammonium
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"[Cl-]", // chloride
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"[Br-]", // bromide
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"[I-]", // iodide
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"[OH-]", // hydroxide
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// Inorganic bases/acids
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"[Na]O", // NaOH
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"O=S(=O)(O)O", // sulfuric acid
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// Drying agents / dessicants
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"O=S(Cl)Cl", // thionyl chloride (reagent but bonds don't map)
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"[Mg+2]", // magnesium ion
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"[Ca+2]", // calcium ion
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"[Zn]", // zinc
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// Borohydride / cyanoborohydride (reducing agents)
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"[BH4-]", // borohydride
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"[BH3-]C#N" // cyanoborohydride
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));
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/**
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* Metal elements commonly found in catalysts.
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* Molecules containing these are likely catalysts, not reactants.
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*/
107+
private static final Set<String> CATALYST_METALS = new HashSet<>(Arrays.asList(
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"Pd", "Pt", "Rh", "Ru", "Ir", "Ni", "Cu", "Fe",
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"Co", "Mn", "Ti", "Zr", "Mo", "W", "Os", "Ag", "Au"
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));
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53112
/**
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* Standardize a reaction: clean mappings, validate balance, build containers.
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*
@@ -132,55 +191,80 @@ public IReaction filterReagents(IReaction reaction) {
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List<IAtomContainer> keptReactants = new ArrayList<>();
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List<IAtomContainer> reagents = new ArrayList<>();
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194+
// Generate canonical SMILES for known-reagent lookup
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org.openscience.cdk.smiles.SmilesGenerator smiGen =
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new org.openscience.cdk.smiles.SmilesGenerator(
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org.openscience.cdk.smiles.SmiFlavor.Canonical);
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135199
for (IAtomContainer reactant : reaction.getReactants().atomContainers()) {
136200
boolean isReagent = false;
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String reason = "";
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137203
try {
138-
org.openscience.cdk.fingerprint.IBitFingerprint reactantFP = fp.getBitFingerprint(reactant);
139-
140-
// Find max similarity to any product
141-
double maxSim = 0.0;
142-
for (org.openscience.cdk.fingerprint.IBitFingerprint prodFP : productFPs) {
143-
if (prodFP != null) {
144-
double sim = Tanimoto.calculate(reactantFP, prodFP);
145-
maxSim = Math.max(maxSim, sim);
146-
}
204+
// Check 1: Known solvent/reagent by canonical SMILES
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String canSmiles = smiGen.create(reactant);
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if (KNOWN_REAGENT_SMILES.contains(canSmiles)) {
207+
isReagent = true;
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reason = "known reagent/solvent: " + canSmiles;
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}
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149-
// If no product resembles this reactant, it's likely a reagent
150-
if (maxSim < 0.3 && reactant.getAtomCount() > 0) {
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// Double-check: does any atom type in this molecule appear
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// exclusively in the reactant (i.e., removed in products)?
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// If so, it might still be a real reactant (leaving group)
154-
boolean hasUniqueContribution = false;
155-
Map<String, Integer> reactantAtomCounts = new LinkedHashMap<>();
211+
// Check 2: Contains catalyst metal
212+
if (!isReagent) {
156213
for (IAtom atom : reactant.atoms()) {
157-
reactantAtomCounts.merge(atom.getSymbol(), 1, Integer::sum);
158-
}
159-
// Check if this reactant contributes atoms not in products
160-
for (Map.Entry<String, Integer> entry : reactantAtomCounts.entrySet()) {
161-
if (!productAtomCounts.containsKey(entry.getKey())) {
162-
hasUniqueContribution = true;
214+
if (CATALYST_METALS.contains(atom.getSymbol())) {
215+
isReagent = true;
216+
reason = "catalyst metal: " + atom.getSymbol();
163217
break;
164218
}
165219
}
220+
}
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167-
// Only filter if: low similarity AND no unique atom contribution
168-
// AND molecule is small (≤ 10 heavy atoms) — large molecules
169-
// are more likely to be real reactants
170-
int heavyAtomCount = 0;
171-
for (IAtom atom : reactant.atoms()) {
172-
if (!"H".equals(atom.getSymbol())) heavyAtomCount++;
222+
// Check 3: Tanimoto fingerprint similarity
223+
if (!isReagent) {
224+
org.openscience.cdk.fingerprint.IBitFingerprint reactantFP =
225+
fp.getBitFingerprint(reactant);
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227+
double maxSim = 0.0;
228+
for (org.openscience.cdk.fingerprint.IBitFingerprint prodFP : productFPs) {
229+
if (prodFP != null) {
230+
double sim = Tanimoto.calculate(reactantFP, prodFP);
231+
maxSim = Math.max(maxSim, sim);
232+
}
173233
}
174-
if (!hasUniqueContribution && heavyAtomCount <= 10) {
175-
isReagent = true;
176-
LOGGER.debug("Filtered reagent/solvent: " + reactant.getID()
177-
+ " (Tanimoto=" + String.format("%.2f", maxSim)
178-
+ ", atoms=" + heavyAtomCount + ")");
234+
235+
if (maxSim < 0.4 && reactant.getAtomCount() > 0) {
236+
// Check for unique atom contribution
237+
boolean hasUniqueContribution = false;
238+
Map<String, Integer> reactantAtomCounts = new LinkedHashMap<>();
239+
for (IAtom atom : reactant.atoms()) {
240+
reactantAtomCounts.merge(atom.getSymbol(), 1, Integer::sum);
241+
}
242+
for (Map.Entry<String, Integer> entry : reactantAtomCounts.entrySet()) {
243+
if (!productAtomCounts.containsKey(entry.getKey())) {
244+
hasUniqueContribution = true;
245+
break;
246+
}
247+
}
248+
249+
int heavyAtomCount = 0;
250+
for (IAtom atom : reactant.atoms()) {
251+
if (!"H".equals(atom.getSymbol())) heavyAtomCount++;
252+
}
253+
254+
if (!hasUniqueContribution && heavyAtomCount <= 10) {
255+
isReagent = true;
256+
reason = "low Tanimoto=" + String.format("%.2f", maxSim)
257+
+ ", atoms=" + heavyAtomCount;
258+
}
179259
}
180260
}
181261
} catch (Exception e) {
182-
// If fingerprinting fails, keep the molecule as reactant
183-
LOGGER.debug("Fingerprint failed for " + reactant.getID() + ": " + e.getMessage());
262+
LOGGER.debug("Filter check failed for " + reactant.getID()
263+
+ ": " + e.getMessage());
264+
}
265+
266+
if (isReagent) {
267+
LOGGER.debug("Filtered: " + reason);
184268
}
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186270
if (isReagent) {

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