Hybrid Supports for Oligonucleotide Synthesis. II. Controlled Pore Glass Derivatized With Multi‐Amine Linear or Branched Polymers

Controlled pore glass (CPG) supports with varying pore sizes and specific surface areas ( A ) were chemically modified to improve their suitability for amine functionalization and oligonucleotide (ON) solid‐phase synthesis. The modification strategy involved two consecutive stages: (i) tuning surface reactivity using combined silane‐based pro‐adhesive layers composed of epoxide‐terminated [8‐(glycidyloxy)‐ n ‐octyl]trimethoxysilane and amine‐inert trimethoxyphenylsilane, and (ii) grafting of high‐molecular‐weight branched poly(ethylene imine) ( b ‐PEI, M n = 10 kDa) or linear poly(allyl amine) (PAA, M w = 65 kDa). The resulting hybrid supports were evaluated in terms of amine group density, loading capacity (l.c.), and ON synthesis performance. Both polymeric modifiers produced linear correlations between l.c. and A, but nonlinear relationships between amine density and A , reflecting steric limitations and polymer architecture effects. A modest but reproducible trityl cation scavenging effect was observed for highly porous b ‐PEI‐modified supports, indicating that triethylsilane addition during detritylation improves synthesis efficiency. ON chain growth was further analyzed by determining the maximal penetration depth ( d max ) of a Cy5‐labeled probe within polymer‐modified CPG. A quantitative correlation between d max and ON yield or purity establishes fluorescence microscopy as a practical structural‐performance descriptor for polymer‐modified supports.