Large Language Models (LLMs) have significantly advanced molecular discovery, but existing multimodal molecular architectures fundamentally rely on autoregressive (AR) backbones. This strict left-to-right inductive bias is sub-optimal for generating chemically valid molecules, as it struggles to account for non-local global constraints (e.g., ring closures) and often accumulates structural errors during sequential generation. To address these limitations, we propose MolDA (Molecular language model with masked Diffusion with mAsking), a novel multimodal framework that replaces the conventional AR backbone with a discrete Large Language Diffusion Model. MolDA extracts comprehensive structural representations using a hybrid graph encoder, which captures both local and global topologies, and aligns them into the language token space via a Q-Former. Furthermore, we mathematically reformulate Molecular Structure Preference Optimization specifically for the masked diffusion. Through bidirectional iterative denoising, MolDA ensures global structural coherence, chemical validity, and robust reasoning across molecule generation, captioning, and property prediction.
Figures & tables
Figure 1: MolDA architecture overview. A hybrid graph encoder (GINE + TokenGT) produces structural representations, the Q-Former maps them into the language model token space, and LLaDA generates the response through iterative denoising with low-confidence remasking.
Generation
Captioning
Regression
Classification
Model
Exact ↑
MACCS ↑
R-1 ↑
METEOR ↑
LogD ↓
HOMO ↓
HIV ↑
SIDER ↑
MolT5-Large
.331
.868
.539
.480
-
-
-
-
Mol-LLM
.415
.873
.570
.471
0.981
.004
.774
.743
Galactica
.000
.178
.105
.065
2.534
.230
.550
.533
LlaSMol
.253
.827
.494
.426
1.582
.982
.685
.622
ChemDFM
.421
.891
.377
.301
5.886
.183
.551
.540
Table 1: Molecular understanding results on ChEBI-20 (Generation, Captioning) and MoleculeNet (Property Prediction). Best results are bolded , second best are underlined .
Forward Synthesis
Retrosynthesis
Reagent Prediction
Model
Exact ↑
MACCS ↑
Exact ↑
MACCS ↑
Exact ↑
MACCS ↑
Mol-LLM
.904
.985
.512
.887
.134
.535
Galactica
.000
.215
.000
.283
.000
.134
LlaSMol
.038
.676
.026
.650
.000
.200
ChemDFM
.302
.808
.080
.769
.000
.229
3D-MoLM
.000
.639
.000
.810
.000
.175
Table 2: Reaction prediction results on Mol-Instructions. Best results are bolded , second best are underlined .