Porous polymer monoliths containing large through-pores were introduced more than 20 years ago.1 The first generation of monoliths exhibited small surface areas of only a few tens of m2/g,which made them an ideal stationary phase for the fast separations of large molecules.However,the absence of small pores represented a challenge in achieving efficient separations of small molecules.This deficiency has led to studies focused on improving the separations of small molecules using polymer monoliths through manipulation of polymerization mixture composition,termination of the polymerization process before reaching complete conversion,use of reversible addition-fragmentation chain polymerization,or polymerization of a single cross-linker.2 We recently demonstrated second generation monoliths exhibiting surface areas as large as several hundreds m2/g that were prepared using a two-step approach that included (i) preparation of a poly(styrene-co-vinylbenzyl chloride-co-divinylbenzene) monolith and (ii) its in situ hypercrosslinking via a Friedel-Crafts alkylation.3 Although these monoliths enabled excellent separations of small molecules,their applications were limited to the reversed phase as dictated by their hydrophobic chemistry.In this work,a novel approach to porous polymer monoliths that are first hypercrosslinked to obtain large surface areas and then modified with zwitterionic functionalities through the attachment of gold nanoparticles in a layered architecture has been developed.These capillary columns were used for the separation of small molecules in hydrophilic interaction liquid chromatography mode (HILIC).Specifically,a monolith with a very large surface area of 430 m2/g was prepared by hypercrosslinking of a generic poly(4-methylstyrene-co-vinylbenzyl chloride-co-divinylbenzene) monolith via a Friedel-Crafts reaction catalyzed with iron chloride.Free radical bromination then provided this hypercrosslinked monolith with 5.7 at.% Br that further reacted with cystamine under microwave irradiation,resulting in a product containing 3.8 at.% sulfur.Clipping the disulfide bonds with tris(2-carboxylethyl)phosphine liberated the desired thiol groups that bind the first layer of gold nanoparticles.These immobilized nanoparticles were an intermediate ligand enabling the attachment of polyethyleneimine as a spacer followed by immobilization of the second layer of gold nanoparticles,which were eventually functionalized with zwitterionic cysteine.Chromatographic performance of these hydrophilic monolithic columns was demonstrated with the separation of mixtures of nucleosides and peptides in HILIC mode.A column efficiency of 51 000 plates/m was achieved for retained analyte cytosine.