Phenol Derivatives as Co-Crystallized Templates to Modulate Trimesic-Acid-Based Hydrogen-Bonded Organic Molecular Frameworks

: Five host − guest trimesic-acid-based hydrogen-bonds framework compounds with different guests, namely [(TMA) 4 · (TMB) 3 ] ( 1 ), [(TMA) 2 · (DMB) 1.5 ] ( 2 ), [(TMA) 6 · (MP)] ( 3 ), [(TMA) · (EP)] ( 4 ) and [(TMA) · (PP)] ( 5 ) (TMA = trimesic acid, TMB = 1,3,5-trimethoxybenzene, DMB = 1,4-dimethoxybenzene, MP = 4-methoxyphenol, EP = 4-ethoxyphenol and PP = 4-propoxyphenol), were obtained through co-crystallization, and were characterized by elemental analysis, infrared spectroscopy analysis, and thermogravimetric analysis. The trimesic acid molecules comprise a hydrogen bonding six-membered cyclic host network that is found in a two-dimensional arrangement in compounds 1 and 2 , and in a nine-fold interpenetrated three-dimensional structure in compound 3 . In compounds 4 and 5 , the trimesic acid and EP/PP molecules form a hydrogen-bonded six-membered cyclic network, resulting in a one-dimensional chain structure through O − H . . . O hydrogen bonds. above-mentioned approaches, ﬁve trimesic acid co-crystallization hydrogen bond systems were obtained by the introduction of small phenols with different derivatives, namely 1,3,5-trimethoxybenzene (TMB), 1,4-dimethoxybenzene (DMB), 4-methoxyphenol (MP), 4-ethoxyphenol (EP), and 4-propoxyphenol (PP) (Scheme 1). hydrogen-bonded networks in trimesic acid, ( II ) structures of trimesic acid and phenol derivatives. ◦ ◦ 1,3,5-trimethoxybenzene Compound ( ) the ﬁrst weight loss from 300 to 362 ◦ C, the observed weight loss of 33.4% (calculated, 33.0%) corresponding to the release of the guest 1,4-dimethoxybenzene molecules. For compound ( 3 ), similar to compound ( 2 ), the ﬁrst weight loss of 48.6% was observed from 300 to 360 ◦ C, corresponding to the release of the trimesic acid, 4-methoxyphenol and solvent molecule. For compound ( 4 ), the two consecutive weight losses of 39.6% in the temperature range of 120–339 ◦ C are close to the theoretical value of 39.7% for the loss of 4-ethoxyphenol. For compound ( 5 ), similar to compound ( 4 ), the two consecutive weight losses with a total of 41.9% in the temperature range of 120–355 ◦ C are close to the theoretical value of 42.0% for the loss of 4-propoxyphenol.


Introduction
The design and assembly of hydrogen-bonded organic frameworks (HOFs) or supramolecular-organic frameworks (SOFs) has attracted intense interest because of the great potential of these frameworks in many materials science and solid-state applications [1][2][3][4][5][6][7][8][9]. Among the various components use in hydrogen-bonded assemblies, multi-carboxylates have been used in numerous HOFs due to the wide variety of their spacers and angles. Trimesic acid (TMA) with the α-polymorph structure with three carboxylate groups was first reported in 1969 [10] and is still an important building block for the construction of HOFs or SOFs due to its predictable honeycomb crystal lattice structure formation [11][12][13]. The crystal structure of the α-polymorph displays the infinite hydrogen-bonded chicken-wire network formed by R 2 2 (8) dimerization of carboxylic acid groups. In the absence of a co-crystal template, TMA constructs infinite two-dimensional hydrogen-bonded networks through eight-member hydrogen bond synthons with hexagonal apertures with a diameter of approximately 14 Å (Scheme 1). Many chemists attempted to remove the concatenation and fill the cavity at the center of the hexametric rings with guest molecules such as tetradecane and pyrenes [14][15][16][17].

Materials and Methods
All the chemicals (98% purity) were obtained from Shanghai Xian Co., Ltd. (Shanghai, China) and were used without further pur analyses were carried out using an Elementar Micro Cube elemental a Germany). Infrared spectra were recorded in the 4000−400 cm −1 regio and a Bruker EQUINOX 55 spectrometer (Bruker, Germany). Thermog were performed using a Netzsch STA 449F3 instrument (Netzsch, G air at a heating rate of 10 °C·min −1 . X-ray powder diffraction data we Bruker D8 ADVANCE X-ray powder diffractometer (Cu Kα radia Bruker, Germany).

Materials and Methods
All the chemicals (98% purity) were obtained from Shanghai Xianding Biotechnology Co., Ltd. (Shanghai, China) and were used without further purification. Elemental analyses were carried out using an Elementar Micro Cube elemental analyzer (Elementar, Hesse, Germany). Infrared spectra were recorded in the 4000−400 cm −1 region using KBr pellets and a Bruker EQUINOX 55 spectrometer (Bruker, Karlsruhe, Germany). Thermogravimetric analyses were performed using a Netzsch STA 449F3 instrument (Netzsch, Bavaria, Germany) in flowing air at a heating rate of 10 • C·min −1 . X-ray powder diffraction data were recorded using a Bruker D8 ADVANCE X-ray powder diffractometer (Cu Kα radiation, λ = 1.5418 Å, Bruker, Germany).

Crystal Structure Determination
Single-crystal data for (1)-(5) were collected using a Bruker Smart Apex II diffractometer (Bruker, Germany) with Mo-Kα radiation (λ = 0.71073 Å). All empirical absorption corrections were applied using the SADABS program [29]. The structures were solved using direct methods that yielded the positions of all non-hydrogen atoms. These positions were refined first isotropically and then anisotropically. All calculations were performed using the SHELXTL software package [30]. The crystallographic data of (1)-(5) are summarized in Table 1. The parameters of the hydrogen bonds in the crystal structures of (1)- (5) are listed in Table 2.  Table 2. Hydrogen bond parameters (Å, • ) for the crystal structures of (1)-(5).
(1)      (1) Co-crystallization of TMA and TMB from a methanol solution gave high-quality crystals that were then characterized by single-crystal X-ray diffraction. It was found that compound (1) crystallizes in a monoclinic cell in the C2/c space group, and contains three TMA and two TMB crystallographically independent molecules per asymmetric unit ( Figure S1). Differences between the three TMA molecules are marginal. The C-O and C=O bond distances of carboxy group are equalized in two TMA molecules. The monomers of compound (1) are interconnected through double hydrogen bonds to form a hexagonal honeycomb motif with hcb topology. The six TMA molecules define a macrocyclic cavity with a diameter of 14 Å. Two types of infinite two-dimensional sheets alternating with one-dimensional channels are formed by three crystallographically independent TMA molecules through O−H···O hydrogen bonding. The first type of sheet is comprised by the first kind of crystallographically independent TMA molecules and the second type of sheet is comprised by the other two kinds of crystallographically independent TMA molecules ( Figure 1). The channels are filled with two types of crystallographically independent guest TMB molecules in a disordered arrangement ( Figure 1). Compound (1) was stabilized by π-π stacking and O-H···O hydrogen bonding interactions.

Quaternary Compound [(TMA)4·(TMB)3] (1)
Co-crystallization of TMA and TMB from a methanol solution gave high-quality crystals that were then characterized by single-crystal X-ray diffraction. It was found that compound (1) crystallizes in a monoclinic cell in the C2/c space group, and contains three TMA and two TMB crystallographically independent molecules per asymmetric unit. Differences between the three TMA molecules are marginal. The C-O and C=O bond distances of carboxy group are equalized in two TMA molecules. The monomers of compound (1) are interconnected through double hydrogen bonds to form a hexagonal honeycomb motif with hcb topology. The six TMA molecules define a macrocyclic cavity with a diameter of 14 Å. Two types of infinite two-dimensional sheets alternating with one-dimensional channels are formed by three crystallographically independent TMA molecules through O−H···O hydrogen bonding. The first type of sheet is comprised by the first kind of crystallographically independent TMA molecules and the second type of sheet is comprised by the other two kinds of crystallographically independent TMA molecules ( Figure 1). The channels are filled with two types of crystallographically independent guest TMB molecules in a disordered arrangement ( Figure 1). Compound (1) was stabilized by π-π stacking and O-H···O hydrogen bonding interactions.
(I) (II) Co-crystallization of TMA and DMB from a methanol solution in a 2:1.5 ratio in an asymmetric unit cell produces compound (2). Single-crystal X-ray diffraction indicates that compound (2) crystallizes in a triclinic cell with the P-1 space group. Similar to

] (2)
Co-crystallization of TMA and DMB from a methanol solution in a 2:1.5 ratio in an asymmetric unit cell produces compound (2) ( Figure S2). Single-crystal X-ray diffraction indicates that compound (2) crystallizes in a triclinic cell with the P-1 space group. Similar to compound (1), the monomers of compound (2) are interconnected through double hydrogen bonds to form a hexagonal honeycomb geometry (Figure 2). The six TMA molecules interact with each other to form a void space with the dimensions of 14 Å × 14 Å through pairwise hydrogen bonding patterns. The crystal contains two types of infinite two-dimensional sheets arranged by two crystallographically independent TMA molecules. The channels are occupied by two types of crystallographically independent guest DMB molecules (Figures 2 and 3). two-dimensional sheets arranged by two crystallographically independent TMA molecules. The channels are occupied by two types of crystallographically independent guest DMB molecules (Figures 2 and 3).

Quaternary Compound [(TMA)6·(MP)] (3)
Co-crystallization of TMA and MP from a methanol solution in a 6:1 ratio in an asymmetric unit cell produced compound (3). Single-crystal X-ray diffraction reveals that the compound (3) crystallizes in a monoclinic cell with the C2/c space group. Similar to a previous report [7], the monomers of compound (3) are interconnected to give a hexagonal honeycomb with a void space dimensions of 14 Å × 14 Å through double hydrogen bonds. The hexagonal honeycombs interact with each other to form waveform two-dimensional sheets, and the infinite waveform two-dimensional sheets concatenated each other to form a three-dimensional structure with cavities occupied by MP molecules (Figure 4). The three-dimensional structure is described as 9-fold interpenetration as shown in Figure 5I in which four identical waveform two-dimensional sheets are chosen randomly and viewed along the b axis. two-dimensional sheets arranged by two crystallographically independent TMA molecules. The channels are occupied by two types of crystallographically independent guest DMB molecules (Figures 2 and 3).

Quaternary Compound [(TMA)6·(MP)] (3)
Co-crystallization of TMA and MP from a methanol solution in a 6:1 ratio in an asymmetric unit cell produced compound (3). Single-crystal X-ray diffraction reveals that the compound (3) crystallizes in a monoclinic cell with the C2/c space group. Similar to a previous report [7], the monomers of compound (3) are interconnected to give a hexagonal honeycomb with a void space dimensions of 14 Å × 14 Å through double hydrogen bonds. The hexagonal honeycombs interact with each other to form waveform two-dimensional sheets, and the infinite waveform two-dimensional sheets concatenated each other to form a three-dimensional structure with cavities occupied by MP molecules (Figure 4). The three-dimensional structure is described as 9-fold interpenetration as shown in Figure 5I in which four identical waveform two-dimensional sheets are chosen randomly and viewed along the b axis.

Quaternary Compound [(TMA) 6 ·(MP)] (3)
Co-crystallization of TMA and MP from a methanol solution in a 6:1 ratio in an asymmetric unit cell produced compound (3) (Figure S3). Single-crystal X-ray diffraction reveals that the compound (3) crystallizes in a monoclinic cell with the C2/c space group. Similar to a previous report [7], the monomers of compound (3) are interconnected to give a hexagonal honeycomb with a void space dimensions of 14 Å × 14 Å through double hydrogen bonds. The hexagonal honeycombs interact with each other to form waveform two-dimensional sheets, and the infinite waveform two-dimensional sheets concatenated each other to form a three-dimensional structure with cavities occupied by MP molecules (Figure 4). The three-dimensional structure is described as 9-fold interpenetration as shown in Figure 5I in which four identical waveform two-dimensional sheets are chosen randomly and viewed along the b axis.

Quaternary Compounds [(TMA)·(EP)] (4) and [(TMA)·(PP)] (5)
Compounds (4) and (5) crystallized from a methanol solution in a 1:1 ratio in a asymmetric unit cell. Single-crystal X-ray diffraction reveals that both compounds (4) an (5) crystallize in a monoclinic cell with the C2/c space group. Unlike compounds (1)-(3 EP/PP replaced two TMA molecules and interconnected to form a tetragonal hole throug O−H···O hydrogen bonding as shown in Figure 5II. The tetragonal holes further interac with each other to form one-dimensional chains ( Figure 6). . Figure 6. One-dimensional hydrogen-bonded chain along the a axis in compounds (4) and (5). Compounds (4) and (5) crystallized from a methanol solu asymmetric unit cell. Single-crystal X-ray diffraction reveals that (5) crystallize in a monoclinic cell with the C2/c space group. U EP/PP replaced two TMA molecules and interconnected to form a O−H···O hydrogen bonding as shown in Figure 5II. The tetrago with each other to form one-dimensional chains ( Figure 6). Compounds (4) and (5) crystallized from a methanol solution in a 1:1 ratio in an asymmetric unit cell ( Figures S4 and S5). Single-crystal X-ray diffraction reveals that both compounds (4) and (5) crystallize in a monoclinic cell with the C2/c space group. Unlike compounds (1)-(3), EP/PP replaced two TMA molecules and interconnected to form a tetragonal hole through O−H···O hydrogen bonding as shown in Figure 5II. The tetragonal holes further interact with each other to form one-dimensional chains ( Figure 6).

Thermogravimetric Analysis
Thermogravimetric analysis (TGA) curves were obtained in flowing air at a heating rate of 10 • C·min −1 in the temperature range from room temperature to 600 • C. Compounds (1)-(5) are air stable and retain their structural integrity at room temperature. The TG curve of compound (1) first shows two consecutive weight losses of 12.2% each from 90 to 180 • C, corresponding to the release of two guest 1,3,5-trimethoxybenzene molecules (calculated, 12.5%), and then another weight loss of 37.8% occurs in the 270-350 • C region, corresponding to the release of four guest 1,3,5-trimethoxybenzene molecules (calculated, 37.5%). The remaining host hydrogen bonding framework began to decompose upon further heating (Figure 7). Compound (2) reveals the first weight loss from 300 to 362 • C, with the observed weight loss of 33.4% (calculated, 33.0%) corresponding to the release of the guest 1,4-dimethoxybenzene molecules. For compound (3), similar to compound (2), the first weight loss of 48.6% was observed from 300 to 360 • C, corresponding to the release of the trimesic acid, 4-methoxyphenol and solvent molecule. For compound (4), the two consecutive weight losses of 39.6% in the temperature range of 120-339 • C are close to the theoretical value of 39.7% for the loss of 4-ethoxyphenol. For compound (5), similar to compound (4), the two consecutive weight losses with a total of 41.9% in the temperature range of 120-355 • C are close to the theoretical value of 42.0% for the loss of 4-propoxyphenol. stals 2021, 11, x FOR PEER REVIEW Thermogravimetric analysis (TGA) curves were obtained in flow rate of 10 °C·min −1 in the temperature range from room temp Compounds (1)-(5) are air stable and retain their structural integrity at The TG curve of compound (1) first shows two consecutive weight l from 90 to 180 °C, corresponding to the release of two guest 1,3,5molecules (calculated, 12.5%), and then another weight loss of 37.8% 350 °C region, corresponding to the release of four guest 1,3,5molecules (calculated, 37.5%). The remaining host hydrogen bondin to decompose upon further heating ( Figure 7). Compound (2) reveals from 300 to 362 °C, with the observed weight loss of 33.4% corresponding to the release of the guest 1,4-dimethoxybenze compound (3), similar to compound (2), the first weight loss of 48.6% 300 to 360 °C, corresponding to the release of the trimesic acid, 4-m solvent molecule. For compound (4), the two consecutive weight los temperature range of 120-339 °C are close to the theoretical value of 3 4-ethoxyphenol. For compound (5), similar to compound (4), the two losses with a total of 41.9% in the temperature range of 120-355 theoretical value of 42.0% for the loss of 4-propoxyphenol.

Conclusions
In conclusion, we have demonstrated that host trimesic acid derivatives form different quaternary co-crystallization compounds by multiple π-π stacking and O-H···O hydrogen bonding interaction

Conclusions
In conclusion, we have demonstrated that host trimesic acid and guest phenol derivatives form different quaternary co-crystallization compounds that were stabilized by multiple π-π stacking and O-H···O hydrogen bonding interactions. The compounds presented here provide an opportunity to further design and construct host-guest organic molecular frameworks with specific structures by co-crystallization. Additionally, it was shown that trimesic acid is a promising chaperone candidate.