Rdkit Chemdraw Cdxml

RDKit ChemDraw / CDXML Toolkit

Overview

CDXML is an XML serialization of ChemDraw's object tree (CDX is its binary form). RDKit 2022.09+ exposes an optional Revvity ChemDraw parser at rdkit.Chem.rdChemDraw that reads molecules and reactions and writes molecule structures. RDKit cannot write arrows, plus signs, schemes, or text — those are built or edited at the XML level. This skill covers the full read → depict → annotate → write → modify → render loop.

Output contract

A .cdxml is not viewable without ChemDraw, and you cannot run ChemDraw here — so the rendered PNG is the only evidence the file is correct. Therefore:

• Deliver <name>.cdxml and <name>.png together, matching basenames — never the CDXML alone. build_scheme() and Module 9 write both; the helper raises if the PNG cannot be produced.
• Validate before delivering with scripts/check_scheme.py (rebuilds each molecule from the drawing, sanitizes, checks mass balance across arrows, and critiques layout). Drive it to zero problems.
• Report honestly: "opens correctly in ChemDraw" is never something you tested; stereochemistry is not drawn unless you added it. Offer a plain SMILES list of intermediates for schemes with more than three structures.

When to Use

• Convert SMILES/SDF/Mol into .cdxml files that open cleanly in ChemDraw
• Extract molecules or reactions (reactants/agents/products) from .cdxml or .cdx
• Build a reaction scheme: fragments + arrows + + separators + conditions text
• Modify an existing ChemDraw file (relabel, annotate, reposition) without losing its arrows/text
• Batch-generate ChemDraw figures for a reaction dataset or SAR table
• Use rdkit-cheminformatics instead for descriptors/fingerprints/SMARTS with no ChemDraw I/O
• For multi-format 3D conversion (MOL2, XYZ, PDB), use openbabel; this toolkit is 2D ChemDraw-specific

Prerequisites

• Python packages: rdkit (2023.03+, built with ChemDraw support), epam.indigo (renders CDXML→PNG); xml.etree.ElementTree (stdlib) handles all XML editing.
• Inputs: SMILES/Mol for writing; .cdxml (UTF-8 text) or .cdx (binary) for reading.
• Check before installing. RDKit is usually already present — run python -c "import rdkit" first; inside pixi use pixi run python ....
• Install epam.indigo into the interpreter that runs your code. A bare pip install can land in a different Python than the kernel (e.g. system /usr/local vs the pixi env that has rdkit), so import indigo still fails even though the install "succeeded" — and no single interpreter then has both rdkit and indigo. In a Jupyter/IPython kernel use %pip install epam.indigo; otherwise python -m pip install epam.indigo (the running interpreter), or add it to the project env (pixi add epam.indigo). For the same reason, do not run the build/render in a fresh subprocess (["python", …] may resolve yet another interpreter) — import the helper and run it in the current process.

python -m pip install epam.indigo   # the running interpreter; or  %pip install epam.indigo  in Jupyter
python -c "from rdkit import Chem; print('ChemDraw write support:', Chem.HasChemDrawCDXSupport())"

Quick Start

from rdkit import Chem
from rdkit.Chem import rdChemDraw, rdDepictor

mol = Chem.MolFromSmiles("CC(=O)Oc1ccccc1C(=O)O")   # aspirin
rdDepictor.SetPreferCoordGen(True)
rdDepictor.Compute2DCoords(mol)                      # coordinates are REQUIRED before writing
cdxml = rdChemDraw.MolToChemDrawBlock(mol, rdChemDraw.CDXFormat.CDXML)   # -> str
open("aspirin.cdxml", "w", encoding="utf-8").write(cdxml)

Core API

Module 1: Reading molecules

MolsFromChemDrawFile / MolsFromChemDrawBlock handle both .cdx and .cdxml, returning a tuple of Mol (one per fragment).

from rdkit import Chem
from rdkit.Chem import rdChemDraw

mols = rdChemDraw.MolsFromChemDrawFile("drawing.cdxml", sanitize=True, removeHs=True)
for m in mols:
    print(Chem.MolToSmiles(m))

block = open("drawing.cdxml", encoding="utf-8").read()
mols = rdChemDraw.MolsFromChemDrawBlock(block, sanitize=True, removeHs=True)
mols_legacy = Chem.MolsFromCDXML(block)   # CDXML-only fallback, no ChemDraw SDK needed

Module 2: Reading reactions (arrows → reactant/product split)

ReactionsFromChemDrawBlock interprets <step>/<arrow> and returns ChemicalReactions with reactants, agents, and products split out. Note the reaction reader defaults sanitize=False.

from rdkit import Chem
from rdkit.Chem import rdChemDraw, rdChemReactions

block = open("reaction.cdxml", encoding="utf-8").read()
for rxn in rdChemDraw.ReactionsFromChemDrawBlock(block, sanitize=True):
    print("reactants:", [Chem.MolToSmiles(m) for m in rxn.GetReactants()])
    print("products :", [Chem.MolToSmiles(m) for m in rxn.GetProducts()])

rxns = rdChemReactions.ReactionsFromCDXMLBlock(block, sanitize=True)   # legacy equivalent

Module 3: Writing molecule structures

MolToChemDrawBlock writes one molecule to CDXML (str). CDX (binary) write is broken in rdChemDraw (UnicodeDecodeError); use the legacy writer for CDX bytes.

from rdkit import Chem
from rdkit.Chem import rdChemDraw, rdDepictor, rdmolfiles

mol = Chem.MolFromSmiles("c1ccccc1O")
rdDepictor.Compute2DCoords(mol)                                          # coords first, always
cdxml = rdChemDraw.MolToChemDrawBlock(mol, rdChemDraw.CDXFormat.CDXML)   # str (preferred)
cdx_bytes = Chem.MolToCDXMLBlock(mol, rdmolfiles.CDXMLFormat.CDX)        # bytes (legacy writer)

Module 4: Good molecular depiction

Layout quality is set before writing. CoordGen gives more natural coordinates; template alignment keeps a shared scaffold oriented consistently across a series. Note: CoordGen still tangles cages and bridged bicyclics — check those in the render.

from rdkit import Chem
from rdkit.Chem import rdDepictor

rdDepictor.SetPreferCoordGen(True)
mol = Chem.MolFromSmiles("O=C(Nc1ccc(cc1)S(=O)(=O)N)C")
rdDepictor.Compute2DCoords(mol)
rdDepictor.StraightenDepiction(mol)
rdDepictor.NormalizeDepiction(mol)      # uniform median bond length

# Align a series to a shared scaffold so the core is drawn identically each time
template = Chem.MolFromSmiles("c1ccc(cc1)S(=O)(=O)N")
rdDepictor.Compute2DCoords(template)
for m in [Chem.MolFromSmiles(s) for s in ["Cc1ccc(cc1)S(=O)(=O)N", "Clc1ccc(cc1)S(=O)(=O)N"]]:
    rdDepictor.GenerateDepictionMatching2DStructure(m, template)

Module 5: Drawing arrows

A reaction arrow is an <arrow> with Head3D/Tail3D ("x y z", y increases downward). ArrowheadHead/ArrowheadType style the head. Equilibrium/resonance/retrosynthetic arrows use a <graphic> Line with ArrowType.

import xml.etree.ElementTree as ET

def make_arrow(arrow_id, tail_xy, head_xy):
    (tx, ty), (hx, hy) = tail_xy, head_xy
    return ET.Element("arrow", {
        "id": str(arrow_id), "FillType": "None", "ArrowheadType": "Solid",
        "ArrowheadHead": "Full", "HeadSize": "2250",
        "BoundingBox": f"{min(tx,hx)} {min(ty,hy)-4} {max(tx,hx)} {max(ty,hy)+4}",
        "Head3D": f"{hx} {hy} 0", "Tail3D": f"{tx} {ty} 0"})

print(ET.tostring(make_arrow(40, (160, 100), (210, 100)), encoding="unicode"))
equil = ET.Element("graphic", {"id": "41", "GraphicType": "Line",
                               "ArrowType": "Equilibrium", "BoundingBox": "160 100 210 100"})

Module 6: Reaction schemes and steps

A <scheme> groups <step> objects that reference page objects by id: ReactionStepReactants, ReactionStepProducts, ReactionStepArrows, ReactionStepPlusses, and objects above/below the arrow.

import xml.etree.ElementTree as ET

def make_plus(gid, x, y):
    return ET.Element("graphic", {"id": str(gid), "GraphicType": "Symbol",
                                  "SymbolType": "Plus", "BoundingBox": f"{x} {y-7} {x+15} {y+8}"})

scheme = ET.Element("scheme", {"id": "60"})
ET.SubElement(scheme, "step", {"id": "61", "ReactionStepReactants": "10 20",
    "ReactionStepProducts": "50", "ReactionStepArrows": "40",
    "ReactionStepPlusses": "30", "ReactionStepObjectsAboveArrow": "70"})
print(ET.tostring(scheme, encoding="unicode"))

Module 7: Adding text and labels

Free text is a <t> at p="x y" holding one or more <s> styled-string children. <s> references a font id (<fonttable>) and color index (<colortable>); face is a bitmask (1=bold, 2=italic, 32=subscript, 64=superscript). Split a <t> into multiple <s> runs for subscripts (Br₂, CO₂H). Indigo renders subscript (32) but not superscript (64) — it drops the run's leading text — so keep charges inline (H+, OH-). °C (temperatures) and Δ (heat) render with the Arial font; avoid other non-Latin-1 characters (hν, en-dashes).

import xml.etree.ElementTree as ET

def make_text(tid, x, y, runs, font_id=21, size=10):
    """runs: list of (text, face). face 0=normal, 1=bold, 32=subscript, 64=superscript."""
    t = ET.Element("t", {"id": str(tid), "p": f"{x} {y}"})
    for text, face in runs:
        ET.SubElement(t, "s", {"font": str(font_id), "size": str(size),
                               "color": "0", "face": str(face)}).text = text
    return t

print(ET.tostring(make_text(70, 175, 92, [("reflux, 2 h", 0)]), encoding="unicode"))
print(ET.tostring(make_text(80, 158, 135, [("Br", 0), ("2", 32), (" (excess)", 0)]),
                  encoding="unicode"))   # Br<sub>2</sub> (excess)

Module 8: Editing an existing CDXML file

ElementTree round-trips arrows, text, and graphics it does not understand, so you can edit a real ChemDraw file without losing objects — unlike an RDKit Mol round-trip.

import xml.etree.ElementTree as ET

tree = ET.parse("reaction.cdxml")          # DOCTYPE is dropped on re-save (harmless)
root = tree.getroot()
for s in root.iter("s"):                   # relabel "Cl" -> "Br"
    if s.text == "Cl":
        s.text = "Br"
cap = ET.SubElement(root.find("page"), "t", {"p": "100 300"})
ET.SubElement(cap, "s", {"font": "21", "size": "12", "color": "0"}).text = "Scheme 1"
tree.write("reaction_edited.cdxml", encoding="unicode", xml_declaration=True)

Module 9: Rendering CDXML to PNG

Render the PNG next to the CDXML (same basename), look at it, then deliver both. Indigo (epam.indigo) loads a CDXML — a scheme with arrows as a reaction, a lone structure as a molecule — and rasterizes arrows, text, and layout faithfully. (RDKit's own Draw.ReactionToImage re-lays-out molecules and drops the ChemDraw arrows/text, so use Indigo to render a file as authored.)

from pathlib import Path
from indigo import Indigo
from indigo.renderer import IndigoRenderer

def render_cdxml(cdxml_path, png_path=None, width=1600):
    png_path = png_path or str(Path(cdxml_path).with_suffix(".png"))
    ind = Indigo(); rnd = IndigoRenderer(ind)
    ind.setOption("render-output-format", "png")
    ind.setOption("render-background-color", "1,1,1")
    ind.setOption("render-image-width", width)
    cdxml = open(cdxml_path, encoding="utf-8").read()
    try:
        obj = ind.loadReaction(cdxml)   # scheme with arrows
    except Exception:
        obj = ind.loadMolecule(cdxml)   # single structure
    rnd.renderToFile(obj, png_path)
    return png_path

print("Wrote", render_cdxml("scheme.cdxml"))

Key Concepts

CDXML coordinate system

y increases downward (origin top-left). Atoms: p="x y"; arrows: Head3D/Tail3D="x y z"; graphics/text: BoundingBox="x1 y1 x2 y2". Default bond length ≈ 30.

def shift_fragment(frag, dx, dy):      # move a fragment onto the canvas
    for n in frag.iter("n"):
        x, y = map(float, n.get("p").split())
        n.set("p", f"{x+dx} {y+dy}")
    return frag

Object-id reference model

Every object has a unique integer id; reactions and groups reference members by id, not by nesting. When merging fragments from separate RDKit outputs (each starts ids at 1), renumber all ids to stay globally unique, then wire <step> to the new ids.

RDKit vs XML capability boundary

Common Workflows

Workflow 1: SMILES → single-molecule CDXML

from rdkit import Chem
from rdkit.Chem import rdChemDraw, rdDepictor

def smiles_to_cdxml(smiles, path):
    mol = Chem.MolFromSmiles(smiles)
    if mol is None:
        raise ValueError(f"Invalid SMILES: {smiles}")
    rdDepictor.SetPreferCoordGen(True)
    rdDepictor.Compute2DCoords(mol)
    rdDepictor.StraightenDepiction(mol)
    open(path, "w", encoding="utf-8").write(rdChemDraw.MolToChemDrawBlock(mol))
    return path

print("Wrote", smiles_to_cdxml("CC(=O)Oc1ccccc1C(=O)O", "aspirin.cdxml"))

Workflow 2: Hand-assemble a reaction from Modules 5-7

Combine _fragment_of (write a mol, extract <fragment>, renumber ids, shift x) with an arrow, a plus, conditions text, and a <step>. Render with Module 9. For multi-step schemes prefer Workflow 4.

from rdkit import Chem
from rdkit.Chem import rdChemDraw, rdDepictor, rdChemReactions
import xml.etree.ElementTree as ET

def _fragment_of(smiles, base_id, dx):
    m = Chem.MolFromSmiles(smiles); rdDepictor.Compute2DCoords(m)
    frag = ET.fromstring(rdChemDraw.MolToChemDrawBlock(m)).find("page/fragment")
    remap = {}
    for i, el in enumerate([frag, *frag.iter("n"), *frag.iter("b")]):
        remap[el.get("id")] = str(base_id + i); el.set("id", remap[el.get("id")])
    for b in frag.iter("b"):
        b.set("B", remap[b.get("B")]); b.set("E", remap[b.get("E")])
    for n in frag.iter("n"):
        x, y = map(float, n.get("p").split()); n.set("p", f"{x+dx} {y}")
    return frag

root = ET.Element("CDXML", {"BondLength": "30"}); page = ET.SubElement(root, "page")
page.append(_fragment_of("CCO", 100, 0))
ET.SubElement(page, "graphic", {"id": "30", "GraphicType": "Symbol",
                                "SymbolType": "Plus", "BoundingBox": "60 -7 75 8"})
page.append(_fragment_of("CC(=O)O", 200, 120))
ET.SubElement(page, "arrow", {"id": "40", "FillType": "None", "ArrowheadHead": "Full",
    "ArrowheadType": "Solid", "HeadSize": "2250", "Head3D": "320 3 0", "Tail3D": "260 3 0"})
cond = ET.SubElement(page, "t", {"id": "70", "p": "270 -12"})
ET.SubElement(cond, "s", {"font": "21", "size": "9", "color": "0"}).text = "H+, reflux"
page.append(_fragment_of("CCOC(C)=O", 300, 420))
scheme = ET.SubElement(page, "scheme", {"id": "60"})
ET.SubElement(scheme, "step", {"id": "61", "ReactionStepReactants": "100 200",
    "ReactionStepProducts": "300", "ReactionStepArrows": "40", "ReactionStepPlusses": "30"})
ET.SubElement(ET.SubElement(root, "fonttable"), "font",
              {"id": "21", "charset": "x-mac-roman", "name": "Helvetica"})

cdxml = ET.tostring(root, encoding="unicode")
open("esterification.cdxml", "w", encoding="utf-8").write(cdxml)
print("reactions re-parsed:", len(rdChemReactions.ReactionsFromCDXMLBlock(cdxml, sanitize=True)))

Workflow 3: Edit an existing file, preserving arrows and text

import xml.etree.ElementTree as ET

tree = ET.parse("input_reaction.cdxml"); root = tree.getroot()
title = ET.SubElement(root.find("page"), "t", {"p": "50 -30"})
ET.SubElement(title, "s", {"font": "21", "size": "14", "color": "0", "face": "1"}).text = "Route A"
for arrow in root.iter("arrow"):
    arrow.set("HeadSize", "3000")
tree.write("output_reaction.cdxml", encoding="unicode", xml_declaration=True)

Workflow 4: Multi-step scheme with the bundled helper (recommended)

scripts/build_reaction_scheme.py turns (smiles, name, conditions) steps into a laid-out scheme and its PNG in one call, handling grid layout, globally unique ids, single arrows, and conditions text placed clear of structures — the defects that recur when schemes are hand-built. Cells auto-size to the largest structure, so big molecules never overlap. Model convergent/multi-component steps by folding co-reactants into conditions (e.g. ["+ (MeO2C)2C=CHOMe", "Base, MeCN"]), keeping one main-chain structure per cell.

Copy the scripts into your working directory with your file tools — not from Python. Inside the execution sandbox the /SciAgent-Skills/... path is reachable only through your read-file tool; it is not on the sandbox filesystem, so a Python open() or import of that path fails with FileNotFoundError/ModuleNotFoundError. For each of build_reaction_scheme.py and check_scheme.py (each is self-contained — rdkit + epam.indigo only — copy just what you need):

1. Read-file tool on /SciAgent-Skills/skills/structural-biology-drug-discovery/rdkit-chemdraw-cdxml/scripts/<name> (the leading slash routes to the skills backend) → returns the script text.
2. Write-file tool → save it to ./<name> in the working directory.

Then import the local copies. (Importing writes a harmless __pycache__/; set PYTHONDONTWRITEBYTECODE=1 to suppress it.)

from build_reaction_scheme import build_scheme    # local copies, already in the workdir
from check_scheme import check_all

steps = [
    {"smiles": "O=C1CCCC1", "name": "cyclopentanone"},
    {"smiles": "O=C1C(Br)C(Br)C(Br)C1Br", "name": "tetrabromoketone",
     "conditions": ["Br2 (excess)", "AcOH, 25 C"]},          # reagents for the arrow into this step
    {"smiles": "O=C1C=CC=C1Br", "name": "2-bromocyclopentadienone",
     "conditions": ["Et2NH", "cold Et2O"]},
    {"smiles": "C12C3C4C1C5C2C3C45", "name": "cubane", "conditions": ["(remaining steps)"]},
]
cdxml, png = build_scheme(steps, "cubane.cdxml", title="Total Synthesis of Cubane", cols=4)
check_all("cubane.cdxml", expect={3: "C12C3C4C1C5C2C3C45"})   # validate before delivering
print(f"Deliverables: {cdxml} + {png}")

Key Parameters

Best Practices

1. Compute 2D coordinates before writing (SetPreferCoordGen(True) then Compute2DCoords); a molecule without coordinates writes as a degenerate layout.
2. Never round-trip a reaction through a Mol if you need the drawing — reading drops arrows, plus signs, text, and graphics. Edit reaction files on the XML tree (Module 8).
3. Keep object ids globally unique. Merging RDKit outputs (each starts at 1) collides and breaks <step> references and doubles arrows; renumber into disjoint blocks.
4. Prefer CDXML (text) over CDX (binary). CDX write via rdChemDraw raises UnicodeDecodeError; only legacy Chem.MolToCDXMLBlock(mol, CDXMLFormat.CDX) returns valid CDX bytes.
5. Write a complete document header — <CDXML BondLength=...> plus a standard <fonttable>/<colortable> and page dimensions. See references/cdxml-schema-reference.md.
6. Text: use °C for temperatures and Δ for heat (both render); keep charges inline (H+, OH-) since Indigo has no superscript; avoid other non-Latin-1 characters. Render heteroatoms via <n Element=...>, not free <t> text; don't add decorative flags ("Chiral"/"racemic") — use wedge bonds. Keep labels clear of the arrow line: names under the structure, conditions offset above/beside the arrow. (build_scheme does all of this — 0 C→0 °C, heat→Δ, subscripts, spacing — automatically.)
7. Deliver the CDXML and PNG together, and run check_scheme.check_all first. The render and the critic catch overlaps, duplicate/degenerate arrows, dropped intermediates, and connectivity errors before the user sees them.

Common Recipes

Recipe: Batch SMILES → CDXML files

from rdkit import Chem
from rdkit.Chem import rdChemDraw, rdDepictor
from pathlib import Path

rdDepictor.SetPreferCoordGen(True); Path("out").mkdir(exist_ok=True)
for i, smi in enumerate(["CCO", "c1ccccc1", "CC(=O)O"]):
    m = Chem.MolFromSmiles(smi); rdDepictor.Compute2DCoords(m)
    Path(f"out/mol_{i}.cdxml").write_text(rdChemDraw.MolToChemDrawBlock(m), encoding="utf-8")

Recipe: Pretty-print CDXML for inspection

import xml.dom.minidom as minidom
print(minidom.parseString(open("esterification.cdxml", encoding="utf-8").read())
      .toprettyxml(indent="  ")[:1500])

Troubleshooting

Bundled Resources

The scripts/ files can be read from the skill path but not imported from there — copy the one you need into your working directory (read_file it, write locally), then import or run it (see Workflow 4 for the exact copy snippet). Each is self-contained and depends only on rdkit (+ epam.indigo).

• references/cdxml-schema-reference.md — element/attribute cheat-sheet (n, b, arrow, graphic, step/scheme, t/s, fonttable, colortable), coordinate conventions, enum tables, and a copy-paste document header.
• scripts/build_reaction_scheme.py — assemble a multi-step scheme from (smiles, name, conditions) steps and render the PNG in one call; auto-sizes cells so structures never overlap. Library (build_scheme(...)) or CLI (python build_reaction_scheme.py steps.json out.cdxml out.png "Title").
• scripts/check_scheme.py — pre-delivery validator/critic. check_all(path, expect=..., perspective_ids=...) rebuilds each molecule from the drawing, sanitizes, prints formulas for a mass-balance check, and flags duplicate ids, fragment overlaps, degenerate arrows, non-ASCII text, decorative flag words ("Chiral"), and labels sitting on an arrow line.

Related Skills

• rdkit-cheminformatics — descriptors, fingerprints, SMARTS; analysis once molecules are parsed
• datamol-cheminformatics — higher-level RDKit wrapper for batch standardization before drawing
• openbabel — multi-format 2D/3D conversion when you need formats beyond ChemDraw

References

• RDKit rdkit.Chem.rdChemDraw — MolsFromChemDraw*, ReactionsFromChemDraw*, MolToChemDrawBlock, CDXFormat
• RDKit depiction docs — 2D coordinates and CoordGen
• CDX/CDXML format specification (CambridgeSoft SDK mirror) — arrows, graphics, reactions, text
• RDKit CDXML test fixtures — real ChemDraw-authored .cdxml
• Indigo toolkit (epam.indigo) — CDXML loading and PNG rendering