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. 2026 Feb 22;11(9):15328–15336. doi: 10.1021/acsomega.5c12770

Fabrication of MOF-Functionalized Silica Monoliths and Their Unique Retention Behavior in HPLC

Keigo Matsubara †, Nobuhiko Hosono ‡, Takashi Uemura ‡, Sayaka Konishi-Yamada §, Takuya Kubo †,§,*
PMCID: PMC12980439  PMID: 41835502

Abstract

We report the development and characterization of stationary phases based on metal–organic frameworks (MOFs) composed of metal ions and organic ligands for use in high-performance liquid chromatography (HPLC). In particular, we focus on a subnanoporous MOF, [Zn2(1,4-ndc)2(ted)] n (Zn-NDC; ndc = naphthalenedicarboxylate, ted = triethylenediamine), exploiting its intrinsic molecular adsorption and recognition capabilities to enhance chromatographic selectivity and efficiency. Zn-NDC was successfully immobilized onto silica monoliths through surface modification. The silica monolith substrate, functionalized with tertiary amine groups, enabled the stable and uniform attachment of Zn-NDC, leading to the successful preparation of a silica monolith modified with Zn-NDC (MOF-monolith). The MOF-monolith column exhibited distinct chromatographic behavior compared with a conventional packed-bed MOF column containing bulk Zn-NDC particles, suggesting that the continuous porous structure and surface chemistry of the silica monolith significantly influence analyte retention mechanisms. Furthermore, when C18 fatty acid methyl esters were employed as analytes, the addition of ether compounds to a mobile phase dramatically altered their elution times and produced sharp, symmetric peak shapes. This phenomenon implies the existence of specific interactions between the ether functionalities and the Zn-NDC framework, highlighting the potential of MOF–silica hybrid monoliths as tunable and efficient stationary phases for advanced HPLC separations.

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1. Introduction

Metal–organic frameworks (MOFs), crystalline coordination polymers constructed from metal ions (or clusters) and organic ligands, have emerged as a highly versatile class of porous materials due to their well-defined pore architectures, large surface areas, and tunable chemical functionalities. − Unlike conventional porous supports such as silica gels or polymeric resins, MOFs can be rationally designed at the molecular level, allowing precise control over pore size, geometry, and surface chemistry. − Owing to these features, MOFs have been widely studied for applications in gas adsorption and separation, catalysis, sensing, and, more recently, as functional stationary phases in liquid chromatography. −

In high-performance liquid chromatography (HPLC), the utilization of MOFs as stationary phases offers an opportunity to introduce molecular-recognition capability into separation media. − However, several challenges hinder their practical use. When crystalline MOF particles are packed into columns, heterogeneity in particle size and morphology, poor packing density, and irregular flow channels lead to nonuniform flow distribution, increasing back pressure and decreasing separation efficiency. ,,, In addition, the fundamental mechanisms of analyte retention in MOF-based stationary phases are still insufficiently understood. Multiple factors, such as pore accessibility, π–π stacking, hydrogen bonding, dipole–dipole interactions, and framework flexibility, can contribute to retention, but their relative roles remain unclear. ,

Among various MOFs, a subnanoporous [Zn2(1,4-ndc)2 ted] n framework (hereafter referred to as Zn-NDC; ndc = 1,4-naphthalenedicarboxylate, ted = triethylenediamine) has attracted particular attention. Uemura and co-workers demonstrated that Zn-NDC can discriminate poly­(ethylene glycol) (PEG) chains based on subtle differences in their terminal structures and polarities through selective insertion into the nanochannels. − This finding opened the possibility of using Zn-NDC as a stationary phase capable of precise molecular recognition. Most recently, Matsubara et al. reported the fabrication of Zn-NDC-based separation columns and demonstrated molecular recognition for linear polymers with closely related terminal structures. These works underline the potential of Zn-NDC as a tunable, selective stationary phase for a polymer and small-molecule separations in HPLC.

Nevertheless, the use of MOF crystalline particles in packed columns still limits chromatographic efficiency due to nonuniform flow and mass-transfer resistance. Recent mechanistic studies, such as those by Torimoto et al., have identified intraparticle diffusion and subnanopore diffusion as key factors governing band broadening in MOF-based HPLC columns. , This mechanistic understanding suggests that improving transport pathways, for example, by integrating MOFs with a continuous porous substrate, could significantly enhance the performance.

Silica monolithic columns offer such an architectural advantage. Unlike packed beds, monolithic silica columns consist of a continuous porous rod featuring interconnected macropores and mesopores, which enable high permeability, low back pressure, and efficient mass transport. − The combination of MOFs and silica monoliths has recently been proposed as a hybrid approach to overcome particle-packing heterogeneity while maintaining molecular selectivity. ,

In this study, we developed a Zn-NDC-modified silica monolithic column (hereafter denoted as an MOF-monolith column) by immobilizing the MOF onto a tertiary amine-functionalized silica substrate. The resulting hybrid column was evaluated in HPLC using C18 fatty acid methyl esters as analytes. We compared its retention and peak profiles with those obtained from a conventional packed-bed MOF column containing bulk Zn-NDC particles. We hypothesized that the monolithic support modifies flow and mass-transport properties, leading to an enhancement of separation efficiency and distinct retention behavior. Our results contribute to understanding how a substrate architecture affects MOF–analyte interactions and provide design guidelines for high-performance MOF–silica hybrid stationary phases.

2. Materials and Methods

2.1. Fabrication of MOF-Modified Silica Monolithic Columns

Before the preparation of MOF-modified silica monolithic columns, the bulk-type monolith was prepared and modified following Scheme . The prepared monoliths were evaluated with X-ray powder diffraction (XRPD) and scanning electron microscope energy dispersive X-ray spectroscopy (SEM-EDX). MOF-modified silica monolithic columns were fabricated by flowing the MOF precursor solution after commercially available silica monolithic capillary columns were modified with tertiary amines using the same procedure described in Scheme . Silica monolithic capillaries were purchased from Shinwa Chemical Co. (Kyoto, Japan). The length of the original column was approximately 700 mm, and we cut the column by hand to test the effects of modifications.

1. Preparation of MOF-Modified Silica Monolith.

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2.1.1. Preparation of an Amino-Modified Silica Monolith (Amino-Monolith)

  • (1)

    1 M HCl aq. was flowed to the silica monolithic capillary column (Si-Monolith) at elevated pressure (1.0 MPa) by N2 gas at 40 °C for 3 h.

  • (2)

    The column was washed with flowing water, methanol, THF, and toluene.

  • (3)

    After the DMAPTMS toluene solution was flowed at room temperature for 24 h, the column was washed with flowing toluene. (The nano HPLC pump was utilized for a single solvent.)

MOF modification was implemented in the tertiary amine-modified column. The fabricated columns were evaluated by observing the retention behavior of acid–base substances in chloroform and that of C18 straight-chain fatty acid methyl esters in hexane.

2.1.2. Preparation of MOF-Modified Silica Monolith (MOF-Monolith)

  • (1)

    1 M HCl aq. was flowed to silica monolith capillary column at elevated pressure (1.0 MPa) by N2 at 40 °C for 3 h.

  • (2)

    The column was washed with flowing water, methanol, THF, and toluene.

  • (3)

    After flowing 7.5% v/v [3-(N,N-dimethylamino)­propyl]­trimethoxysilane (DMAPTMS) toluene solution at room temperature for 24 h, the column was washed with flowing toluene.

  • (4)

    After the MOF precursor solution was flowed at elevated pressure with N2 gas at room temperature for 48 h, the column was washed with flowing DMF.

The MOF precursor was prepared by mixing 200 mM Zn­(NO3)2·6H2O in DMF solution: (A) 10 mM triethylenediamine and and 20 mM 1,4-naphthalenedicarboxylic acid in DMF solution: (B) MOF-Monolith-1, A/B = 1/6 (v/v); MOF-Monolith-2, A/B = 1/7 (v/v); and MOF-Monolith-3, A/B = 1/8 (v/v) were examined.

2.2. HPLC Evaluations for the Prepared Monoliths

For microflow HPLC analyses, we utilized a Nexera Mikros (SHIMADZU Co., Kyoto, Japan). In all HPLC analyses, we employed normal phase conditions because adding water to a mobile phase could cause a strong hydrophobic interaction between the columns and analytes.

Condition 1

Column: Si-Monolith (351 mm × 100 μm i.d.), Amino-Monolith (350 mm × 100 μm i.d.). Injection volume of analytes: 20 nL, Measurement temperature: 40 °C, Flow rate: 1 μL/min, Detection: UV (245 nm), Mobile phase: chloroform, Analytes: benzene (1 mg/mL), toluene (1 mg/mL), pyridine (1 mg/mL), and phenol (0.2 mg/mL).

Condition 2

Column: Si-Monolith (351 mm × 100 μm i.d.), Amino-Monolith (350 mm × 100 μm i.d.), MOF-Monolith-1 (349 mm × 100 μm i.d.), MOF-Monolith-2 (350 mm × 100 μm i.d.), MOF-Monolith-3 (351 mm × 100 μm i.d.), Injection volume of analytes: 20 nL, Measurement temperature: 40 °C, Flow rate: 1 μL/min, Detection: UV (254 and 220 nm), Mobile phase: chloroform and hexane, Analytes: benzene (1 mg/mL), toluene (1 mg/mL), pyridine (1 mg/mL), phenol (0.2 mg/mL), and C18 fatty acid methyl esters (see Table , saturation: 10 mg/mL, liquid: 1 μL/mL, solid: 5 mg/mL).

1. Name and Structure of the C18 Fatty Acid Methyl Esters.

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2.3. Preparation of the Extended MOF-Monolith Columns

After the preparation of Amino-Monolith using the same procedure as above, the MOF precursor solution was flowed at elevated pressure (1.0 MPa) with N2 gas at room temperature for 48 h, and the column was washed with flowing DMF. Then, the MOF precursor was prepared by mixing 200 mM Zn­(NO3)2·6H2O in DMF solution (A), and 10 mM triethylenediamine and 20 mM 1,4-naphthalenedicarboxylic acid in DMF solution (B) at the ratio of A/B = 1/6 (v/v). The column length was extended to 750 mm, and a flowing method was explored. Toluene solution was flowed by elevating the pressure (1 MPa) using N2 gas when tertiary amines were modified; this time, the use of a syringe pump was considered for flowing. The 700 mm column was cut in half after tertiary amine modification, and then the retention behaviors of pyridine and phenol in chloroform in each column were compared. The concentration of the MOF precursor solution was reconsidered.

2.4. Evaluation of C18 Fatty Acid Methyl Esters Using the MOF-Monolith Column

An analysis of C18 fatty acid methyl esters in the mobile phase, hexane, was conducted using the fabricated silica-MOF (750 mm × 100 μm i.d.). An elution behavior changed by adding other organic solvents to the mobile phase was observed.

3. Results and Discussion

3.1. Fabrication of MOF-Modified Silica Columns

Following our previous evaluations, a 10 vol % DMAPTMS toluene solution was applied for tertiary amine modification. Consequently, we observed the small particles caused by DMAPTMS in the capillary, and they blocked the flow path. Figure S1 shows the SEM images of the monoliths with different concentrations of tertiary amine modification. When bulk silica monoliths were modified, in the case of 10 vol % DMAPTMS, the crystals were different from the substrate, while in the case of 5% and 7.5 vol % DMAPTMS, the crystals were not observed. The concentration was thus determined as 7.5% for tertiary amine modification.

Then, the DMAPTMS-modified bulk monolith was treated with an MOF, and the prepared bulk substrates were evaluated with PXRD and SEM-EDX. Figure shows SEM images, the spectra of PXRD, and elemental mapping by EDX. According to these results, qualitative modification of an MOF could be successfully achieved.

1.

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Results of SEM and PXRD for bulk monoliths. (a) SEM images of DMAPTMS-modified bulk monolith (silica-amine) and its MOF modified (silica-MOF), (b) spectra of PXRD for a simuilation of MOF and each monolith, and (c) elemental mapping of silica-MOF by EDX.

Since MOF modification was confirmed with bulk monoliths, the capillary monoliths were examined with HPLC. Figure shows the chromatograms in the mobile phase, chloroform, before and after tertiary amine modification. Benzene and toluene did not retain with both columns. Retention of phenol was increased, and that of pyridine was decreased with tertiary amine modification. This phenomenon can be explained by the fact that silanol groups on the surface of the silica monoliths caused electrostatic interaction with a basic analyte, pyridine; by contrast, silica-tertiary amines generated opposite electrostatic interaction, resulting in longer retention with an acid analyte, phenol. Therefore, we assumed that tertiary amine modification using the silica monoliths had succeeded.

2.

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Chromatograms before and after tertiary amine modification. HPLC conditions: column, Si-Monolith (351 mm × 100 μm i.d.), Amino-Monolith (350 mm × 100 μm i.d.); mobile phase, chloroform; flow rate, 1.0 μL/min; temperature, 40 °C; detection, UV 254 nm.

To determine the optimal concentration of the precursor solution, the ratio of B (triethylenediamine and 1,4-naphthalenedicarboxylic acid) was altered 3–8 times, toward A (Zn­(NO3)2·6H2O) in DMF solution. When modification of the amino-silica was conducted at the concentration of the MOF precursor, A/B = 1/3–5, the MOF crystals were precipitated, and the solution barely flowed. Then the concentration of the MOF precursor was altered to A/B = 1/6–8.

The ends of the capillaries of an original silica monolith, the silica-tertiary amine monolith, and the MOF monoliths prepared with precursors (1), (2), and (3) were cut off and then observed by SEM. All of these structures on the surface of the silica monoliths did not specifically change. Figure shows the retention behaviors of phenol and pyridine in chloroform as the mobile phase in each column. Benzene and toluene were not retained with all columns. With the column modified using Zn-NDC (MOF-monolith), the retention behavior obviously changed in comparison with the Amino-Monolith. In the case of the Amino-Monolith, phenol was retained. The retention decreased with (1) and (2) and increased with (3) compared with the Amino-Monolith. By contrast, in the case of pyridine, the retention may have increased due to the high polarity caused by the larger number of acid–base ligands.

3.

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Retention behavior of phenol and pyridine in chloroform with each column. HPLC conditions: column, Si-Monolith (351 mm × 100 μm i.d.), Amino-Monolith (350 mm × 100 μm i.d.), MOF-Monolith-1 (349 mm × 100 μm i.d.) (A/B = 1/6), MOF-Monolith-2 (350 mm × 100 μm i.d.) (A/B = 1/7), MOF-Monolith-3 (351 mm × 100 μm i.d.) (A/B = 1/8); mobile phase, chloroform; flow rate, 1.0 μL/min; temperature, 40 °C; detection, UV 254 nm.

As changes in retention behavior were observed in the Zn-NDC monolithic column, C18 fatty acid methyl esters in hexane were qualitatively evaluated. Since the retention of C18 fatty acid methyl esters in hexane with Zn-NDC was confirmed, we can verify if the changes derived from Zn-NDC, as shown in Figure . The structures and their abbreviations are summarized in Table . The C18 fatty acid methyl esters were slightly retained with the silica monolith, while differences in retentions were not clearly observed. In addition, none of them retained with the Amino-Monolith. This may be because tertiary amine modification inhibited hydrophilic interaction with silanol groups of the silica monolith and methyl esters. With the MOF-modified column, the retention of C18 fatty acid methyl esters was observed. The retention behaviors with the MOF-modified column, which was prepared at 1/6 (MOF-Monolith-1), were the same as that of the column packed MOF crystal particles in the bulk state. The peak was broad with the column after flowing the MOF precursor solution prepared at 1/7 (MOF-Monolith-2), meaning that the state of MOF modification was poor and homogeneity was low. In addition, the MOF prepared at 1/8 (MOF-Monolith-3) showed lower retention. Taken together, the MOF precursor solution prepared at 1/6 (MOF-Monolith-1) was ideal for the conditions of MOF modification.

4.

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Evaluation of each column in the mobile phase, hexane. HPLC conditions: column, Si-Monolith (351 mm × 100 μm i.d.), Amino-Monolith (350 mm × 100 μm i.d.), MOF-Monolith-1 (349 mm × 100 μm i.d.) (A/B = 1/6), MOF-Monolith-2 (350 mm × 100 μm i.d.) (A/B = 1/7), MOF-Monolith-3 (351 mm × 100 μm i.d.) (A/B = 1/8); mobile phase, hexane; flow rate, 1.0 μL/min; temperature, 40 °C; detection, UV 220 nm.

3.2. Optimization of Column Preparation

To identify the MOF onto the silica monolith, MOF-Monolith-5 was analyzed with SEM, PXRD, and X-ray fluorescence analysis (XRF). The SEM images are summarized in Figure S2. In comparison with Amino-Monolith and MOF-Monolith-5, a morphological change was clearly observed. After both capillary columns, Silica Monolith and MOF-Monolith-5, were crushed, the particles were analyzed. As a result, the amount of MOF was not enough for the detection of valuable spectra of an MOF. However, Zn was detected in the MOF-modified silica monolith capillary, as shown in Table S1. These XRF results suggest the presence of MOF.

Table S2 shows the retention coefficient of phenol and pyridine in chloroform with columns prepared by flowing a tertiary amine solution using N2 gas pressure or the syringe pump. To identify whether the modification was homogeneously implemented, elution behaviors were observed at two sides of the column, the inlet and the outlet, using N2 gas pressure. Consequently, the elution behaviors were clearly different at the inlet and the outlet, meaning that the modification was not uniform. In the case of the ones using a syringe pump, the coefficients were close at both sides. These behaviors revealed that preparing the column using the syringe pump was suitable for the modification of the tertiary amine to the 750 mm column.

7.5% DMAPTMS v/v toluene solution and the MOF precursor solution were flowed using the syringe pump to the Amino-Monolith of a 750 mm column. After 48 h, the flow path was clogged, and the solution was unable to flow in the column. Then, we considered that the concentration should be diluted with DMF at the same mixture ratio of the precursor. To optimize the concentration of the precursor, it was diluted to 1/2 or 3/4 (MOF-Monolith-4 or MOF-Monolith-5, respectively). Consequently, the solution was able to flow without clogging, even after 48 h. Figure shows the chromatograms obtained in the mobile phase, chloroform, before and after the MOF modification. It indicates that changes of retention correspond to the properties of acid/base groups on the surface in each column.

5.

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Results of measurement with the mobile phase, chloroform. Upper, before flowing MOF precursor solution (750 mm length); bottom, after flowing MOF precursor solution diluted at 1/2 (left, MOF-Monolith-4) and 3/4 (right, MOF-Monolith-5). Mobile phase, chloroform; flow rate, 1.0 μL/min; temperature, 40 °C; detection, UV 254 nm.

Figure shows the chromatograms obtained in the mobile phase, hexane. C18 fatty acid methyl esters were retained in both columns. In all of the chromatograms, minor peaks were observed around the dead time, which is almost the same as benzene. These peaks were caused by the impurity of the standard C18 fatty acid methyl esters. In other words, the impurity can be easily removed using the MOF-based columns.

6.

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Results of measurement with the mobile phase, hexane. After MOF modification (left, MOF-Monolith-4) diluted to 1/2 and (right, MOF-Monolith-5) diluted to 3/4. Mobile phase, chloroform; flow rate, 1.0 μL/min; temperature, 40 °C; detection, UV 220 nm.

The order of elution should be benzene < saturation < one CC bond < two CC bonds (cis-9/cis-12). Strong retention and peak tailings were observed with the column-implemented MOF modification at a concentration of 3/4. Because of the strong retention, the concentration of the MOF precursor solution is preferred as 3/4 (v/v) (MOF-Monolith-5) for MOF modification. According to these evaluations, MOF-Monolith-5 was suitable for the separation of C18 fatty acid methyl esters. Unlike columns packed directly with MOF particles, in this case, both the MOF and the residual silanol groups of the silica monolith are considered to influence the retention. Since cis-9/12 is relatively more polar than the other fatty acid methyl esters, its polarity is expected to contribute to this effect. To improve the separation efficiency, the mobile phase conditions are optimized in the next section.

3.3. Evaluation of Retention Behaviors with Different Conditions of a Mobile Phase

Although the strong retention of the C18 fatty acid methyl esters was observed with the MOF-Monolith-5, peak tailing occurred. To make the peak shapes sharper, other types of organic solvents were added to hexane. In this evaluation, the mixture sample was also analyzed to explore the possibility for the separation.

First, we expected that the polar solvents should be used for accelerating the elution of analytes; then, chloroform or 2-propanol was added to hexane. However, the peak of C18 fatty acid methyl esters was difficult to be detected due to chloroform and 2-propanol hampering the absorption wavelength.

Figure shows the chromatograms when methyl tert-butylether (MTBE) was added to the mobile phase. With hexane alone, the last peak (cis-9/12) was observed in 17 min (Figure ), although the elution time became faster as MTBE was added. With hexane/MTBE = 95/5, all peaks were observed in just 4 min. Thus, the elution time of C18 fatty acid methyl esters was affected by competitive MTBE. Based on the analysis results of the saturated ester with hexane alone and hexane/MTBE mixture up to 95/5, the symmetry factor, S, was calculated. S is defined as W0.05h/2f, where W0.05h is the peak width measured at 1/20 of the peak height above the peak baseline. f is the distance along this horizontal line from the leading edge of the peak to the vertical line drawn from the peak apex that bisects W0.05h.

7.

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Chromatograms for C18 fatty acid methyl esters with MTBE as mobile phases. The HPLC conditions are the same as Figure . Column, MOF-Monolith-5; mobile phase, hexane and MTBE.

In the case of S = 1, the peak is symmetric, the tailing peak is S > 1, and the leading peak is S < 1. The results under six conditions were S = 4.14, 11.31, 0.72, 0.91, 1.44, and 1.94, with the volume ratio of MTBE of 0, 0.05, 0.1, 0.5, 1, 5, respectively. The superior peak was obtained with hexane/MTBE = 99.5/0.5. Regarding the plate number using the saturated ester, with hexane/MTBE = 100/0, 99.5/0.5, 99/1, and 95/5, they were 1385, 8145, 14,466, and 12,534, respectively. These results proved that adding MTBE is effective in improving the separation efficiency of columns.

Next, we discuss separation selectivity. With the addition of MTBE, separation of the C18 fatty acid methyl esters was achieved under all tested conditions. Although it remains difficult to separate the cis and trans isomers that contain a single double bond, it is possible to separate saturated species, monodouble bond species, and didouble bond species in the mixture. Here, we compare this behavior with the concept of resolution (R s) in HPLC. − In HPLC, R s is a quantitative measure of how well two adjacent peaks are separated in a chromatogram. It evaluates both the distance between the peak centers and the peak widths.

Resolution is commonly defined by the following equation

Rs=2(tR2−tR1)W1+W2

where

  • t R1 and t R2 are the retention times of the first and second peaks, and

  • W 1 and W 2 are the corresponding baseline peak widths.

A resolution of R s = 1.5 is generally considered sufficient for baseline separation, meaning that the two peaks are essentially fully separated without overlap. Lower values indicate partial separation, while higher values represent better separation.

From the results, when a mobile phase containing 0.5% MTBE was used, the saturated monodouble bond and didouble bond species were each completely separated. These results suggest that the use of MOF enables the separation of fatty acids based on their degree of unsaturation.

With regard to the retention mechanism, detailed discussion is difficult at this stage; however, it is anticipated that the addition of ether-containing solvents inhibits the interaction between the C18 fatty acid methyl esters and the MOF. As a comparative experiment, mobile phases prepared by adding diethyl ether (DEE) or tetrahydrofuran (THF) to hexane were tested, and, as shown in Figure S3, similar separation behavior was observed.

4. Conclusion

To enhance the separation performance, a column was fabricated by modifying a silica monolithic support with an MOF, and this column was used to further investigate the detailed behavior of C18 fatty acid methyl esters, which had previously been analyzed by using a particle-packed column. Although the elution behavior obtained with the MOF-modified monolith differed significantly from that observed with the particle-packed column, it became evident that the peak shapes were strongly influenced by the addition of ether-containing solvents to the hexane mobile phase. This pronounced change in chromatographic behavior suggests the presence of specific interactions between the MOF framework and ether functional groups. Taken together, these findings imply that MOF–analyte and MOF–solvent interactions play a crucial role in governing selectivity and retention, offering new possibilities for tailoring MOF-based stationary phases to achieve improved separations of structurally similar fatty acid derivatives.

Supplementary Material

ao5c12770_si_001.pdf (1,017.2KB, pdf)

Acknowledgments

This work was partly supported by JST, CREST Grant Number JPMJCR2332, JST A-STEP Grant Number JPMJTR214C, and the Environment Research and Technology Development Fund (JPMEERF20235003) of the Environmental Restoration and Conservation Agency of Japan.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.5c12770.

  • Chemicals and HPLC column, Instruments, SEM images of Amino-Monolith and MOF-Monolith-5, Contents of the elements in the capillary columns by XRF, Retention coefficient of phenol and pyridine, and Chromatograms with DEE and THF (PDF)

All authors contributed to and have given approval for the final version of the manuscript. K.T.: Supervision, project administration, funding acquisition, conceptualization, methodology, writingoriginal draft, writingreview and editing; M.K., H.N., and U.T.: Conceptualization, data curation, formal analysis; K.-Y.S.: Writingoriginal draft, writingreview and editing.

The authors declare no competing financial interest.

References

  1. Zhou H.-C., Long J. R., Yaghi O. M.. Introduction to metal–organic frameworks. ACS Publications. 2012;112:673–674. doi: 10.1021/cr300014x. [DOI] [PubMed] [Google Scholar]
  2. James S. L.. Metal-organic frameworks. Chem. Soc. Rev. 2003;32(5):276–288. doi: 10.1039/b200393g. [DOI] [PubMed] [Google Scholar]
  3. Kitagawa S., Kitaura R., Noro Si.. Functional porous coordination polymers. Angew. Chem., Int. Ed. 2004;43(18):2334–2375. doi: 10.1002/anie.200300610. [DOI] [PubMed] [Google Scholar]
  4. Furukawa H., Cordova K. E., O’Keeffe M., Yaghi O. M.. The chemistry and applications of metal-organic frameworks. Science. 2013;341(6149):1230444. doi: 10.1126/science.1230444. [DOI] [PubMed] [Google Scholar]
  5. Férey G.. Hybrid porous solids: past, present, future. Chem. Soc. Rev. 2008;37(1):191–214. doi: 10.1039/B618320B. [DOI] [PubMed] [Google Scholar]
  6. Li J.-R., Kuppler R. J., Zhou H.-C.. Selective gas adsorption and separation in metal–organic frameworks. Chem. Soc. Rev. 2009;38(5):1477–1504. doi: 10.1039/b802426j. [DOI] [PubMed] [Google Scholar]
  7. Kreno L. E., Leong K., Farha O. K., Allendorf M., Van Duyne R. P., Hupp J. T.. Metal–organic framework materials as chemical sensors. Chem. Rev. 2012;112(2):1105–1125. doi: 10.1021/cr200324t. [DOI] [PubMed] [Google Scholar]
  8. Horike S., Shimomura S., Kitagawa S.. Soft porous crystals. Nat. Chem. 2009;1(9):695–704. doi: 10.1038/nchem.444. [DOI] [PubMed] [Google Scholar]
  9. Ding M., Yang L., Zeng J., Yan X., Wang Q.. Orderly MOF-assembled hybrid monolithic stationary phases for nano-flow HPLC. Anal. Chem. 2020;92(24):15757–15765. doi: 10.1021/acs.analchem.0c02706. [DOI] [PubMed] [Google Scholar]
  10. Meng S.-S., Xu M., Han T., Gu Y.-H., Gu Z.-Y.. Regulating metal–organic frameworks as stationary phases and absorbents for analytical separations. Anal. Methods. 2021;13(11):1318–1331. doi: 10.1039/D0AY02310H. [DOI] [PubMed] [Google Scholar]
  11. Mansour O., Kawas G., Rasheed M. A., Sakur A. A.. Applications of metal-organic frameworks (MOFs) to separation analytical techniques. Res. J. Pharm. Technol. 2018;11(8):3514–3522. doi: 10.5958/0974-360X.2018.00650.9. [DOI] [Google Scholar]
  12. Yusuf K., Aqel A., ALOthman Z.. Metal-organic frameworks in chromatography. J. Chromatgr. A. 2014;1348:1–16. doi: 10.1016/j.chroma.2014.04.095. [DOI] [PubMed] [Google Scholar]
  13. Svec F., Lv Y.. Advances and recent trends in the field of monolithic columns for chromatography. Anal. Chem. 2015;87(1):250–273. doi: 10.1021/ac504059c. [DOI] [PubMed] [Google Scholar]
  14. Zhang J., Chen Z.. Metal-organic frameworks as stationary phase for application in chromatographic separation. J. Chromatgr. A. 2017;1530:1–18. doi: 10.1016/j.chroma.2017.10.065. [DOI] [PubMed] [Google Scholar]
  15. Qin W., Silvestre M. E., Kirschhöfer F., Brenner-Weiss G., Franzreb M.. Insights into chromatographic separation using core–shell metal–organic frameworks: Size exclusion and polarity effects. J. Chromatgr. A. 2015;1411:77–83. doi: 10.1016/j.chroma.2015.07.120. [DOI] [PubMed] [Google Scholar]
  16. Hosono N., Uemura T.. Metal-organic frameworks for macromolecular recognition and separation. Matter. 2020;3(3):652–663. doi: 10.1016/j.matt.2020.06.013. [DOI] [Google Scholar]
  17. Hosono N., Uemura T.. Metal–organic frameworks as versatile media for polymer adsorption and separation. Acc. Chem. Res. 2021;54(18):3593–3603. doi: 10.1021/acs.accounts.1c00377. [DOI] [PubMed] [Google Scholar]
  18. Gu Z.-Y., Yang C.-X., Chang N., Yan X.-P.. Metal–organic frameworks for analytical chemistry: from sample collection to chromatographic separation. Acc. Chem. Res. 2012;45(5):734–745. doi: 10.1021/ar2002599. [DOI] [PubMed] [Google Scholar]
  19. Kotova A. A., Thiebaut D., Vial J., Tissot A., Serre C.. Metal-organic frameworks as stationary phases for chromatography and solid phase extraction: A review. Coord. Chem. Rev. 2022;455:214364. doi: 10.1016/j.ccr.2021.214364. [DOI] [Google Scholar]
  20. Hefnawy M., El-Gendy M., Al-Salem H., Marenga H., El-Azab A., Abdel-Aziz A., El Gamal A., Alanazi M., Obaidullah A., Al-Hossaini A., Hefnawy A.. Trends in monoliths: Packings, stationary phases and nanoparticles. J. Chromatgr. A. 2023;1691:463819. doi: 10.1016/j.chroma.2023.463819. [DOI] [PubMed] [Google Scholar]
  21. Torimoto A., Leon E. N., Broeckhoven K., Uemura T., Hosono N., Desmet G.. Mechanistic Insights into Band Broadening in MOF-based Liquid Chromatography: Role of Sub-Nanopore Diffusion and Packing Heterogeneity. J. Chromatgr. A. 2025:466481. doi: 10.1016/j.chroma.2025.466481. [DOI] [PubMed] [Google Scholar]
  22. Kioka K., Mizutani N., Hosono N., Uemura T.. Mixed metal–organic framework stationary phases for liquid chromatography. ACS Nano. 2022;16(4):6771–6780. doi: 10.1021/acsnano.2c01592. [DOI] [PubMed] [Google Scholar]
  23. Mizutani N., Hosono N., Le Ouay B., Kitao T., Matsuura R., Kubo T., Uemura T.. Recognition of polymer terminus by metal–organic frameworks enabling chromatographic separation of polymers. J. Am. Chem. Soc. 2020;142(8):3701–3705. doi: 10.1021/jacs.9b13568. [DOI] [PubMed] [Google Scholar]
  24. Sawayama T., Wang Y., Watanabe T., Takayanagi M., Yamamoto T., Hosono N., Uemura T.. Metal-Organic Frameworks for Practical Separation of Cyclic and Linear Polymers. Angew. Chem., Int. Ed. 2021;133(21):11936–11940. doi: 10.1002/ange.202102794. [DOI] [PubMed] [Google Scholar]
  25. Matsubara K., Watabe Y., Konishi-Yamada S., Hosono N., Uemura T., Kubo T.. Metal–organic framework-based separation columns: fundamental study for molecular recognition and potential for separation of linear polymers with close terminal structures. Analyst. 2025;150(15):3372–3377. doi: 10.1039/D5AN00548E. [DOI] [PubMed] [Google Scholar]
  26. Zhao X., Wang Y., Li D. S., Bu X., Feng P.. Metal–organic frameworks for separation. Adv. Mater. 2018;30(37):1705189. doi: 10.1002/adma.201705189. [DOI] [PubMed] [Google Scholar]
  27. Si H., Wang Q., Guo Y., Zhao Y., Li H., Li S., Wang S., Zhu B.. Functionalized monolithic columns: Recent advancements and their applications for high-efficiency separation and enrichment in food and medicine. Front. Chem. 2022;10:951649. doi: 10.3389/fchem.2022.951649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Staniak M., Wójciak M., Sowa I., Tyszczuk-Rotko K., Strzemski M., Dresler S., Myśliński W.. Silica-based monolithic columns as a tool in HPLCan overview of application in analysis of active compounds in biological samples. Molecules. 2020;25(14):3149. doi: 10.3390/molecules25143149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ali I., Suliman F. E. O., Aboul-Enein H. Y.. Superficially porous and monolithic columns for ultrafast separations in HPLC. LC-GC North Am. 2009;27(4):S22 [Google Scholar]
  30. Peirano S. R., Prince D. L., Giovannoni S., Aguilar E. C., Rafti M., Ceolin M., Keunchkarian S., Echevarría R. N., Reta M.. Hybrid organic monolithic column containing MIL-68 (Al) for the separation of small molecules by capillary HPLC. J. Chromatgr. A. 2024;1733:465258. doi: 10.1016/j.chroma.2024.465258. [DOI] [PubMed] [Google Scholar]
  31. Torimoto A., Ishibashi D., Yamashita A., Uemura T., Hosono N.. High-Precision Separation and Refinement of Fatty Acid Derivatives by Metal–Organic Frameworks. J. Am. Chem. Soc. 2025;147(20):17228–17238. doi: 10.1021/jacs.5c03316. [DOI] [PubMed] [Google Scholar]
  32. Wilson R. E., Groskreutz S. R., Weber S. G.. Improving the sensitivity, resolution, and peak capacity of gradient elution in capillary liquid chromatography with large-volume injections by using temperature-assisted on-column solute focusing. Anal. Chem. 2016;88(10):5112–5121. doi: 10.1021/acs.analchem.5b04793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Fekete S., Bobály B., Nguyen J. M., Beck A., Veuthey J.-L., Wyndham K., Lauber M. A., Guillarme D.. Use of ultrashort columns for therapeutic protein separations. Part 1: theoretical considerations and proof of concept. Anal. Chem. 2021;93(3):1277–1284. doi: 10.1021/acs.analchem.0c04082. [DOI] [PubMed] [Google Scholar]
  34. Hamed N. A., Shread A. K., Morris G. A., Nilsson M.. Transcending Resolution Limits in HPLC and Diffusion NMR. Anal. Chem. 2024;96(52):20475–20480. doi: 10.1021/acs.analchem.4c04418. [DOI] [PMC free article] [PubMed] [Google Scholar]

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