Strong Intramolecular Hydrogen Bond Research Articles

Blockade of persistent colored isomer formation in photochromic 3H-naphthopyrans by excited-state intramolecular proton transfer

In photochemistry the excited-state intramolecular proton transfer process (ESIPT) is often observed as a highly efficient singlet excited state depletion pathway, which in the presence of a strong intramolecular hydrogen bond may proceed on a subpicosecond time scale. The present work describes the suppression of unwanted transoid-trans isomer formation in photochromic 3H-naphthopyran derivatives by the introduction of a 5-hydroxy substituent. According to time-resolved spectroscopy experiments and excited-state ab initio calculations, transoid-cis → transoid-trans photoisomerization is reduced by a competitive ESIPT channel in nonpolar solvent (cyclohexane). Upon specific solute–solvent interactions (methanol, acetonitrile) the intramolecular hydrogen bond in the transoid-cis form is perturbed, favoring the internal conversion S1 → S0 process as photostabilizing channel.

Phosphinous Acid-Phosphinito Tetra-Icosahedral Au52 Nanoclusters for Electrocatalytic Oxygen Reduction.

While the formation of superatomic nanoclusters by the three-dimensional assembly of icosahedral units was predicted in 1987, the synthesis and structural determination of such clusters have proven to be incredibly challenging. Herein, we employ a mixed-ligand strategy to prepare phosphinous acid-phosphinito gold nanocluster Au52(HOPPh2)8(OPPh2)4(TBBT)16 with a tetra-icosahedral kernel. Unlike expected, each icosahedral Au13 unit shares one vertex gold atom with two adjacent units, resulting in a "puckered" ring shape with a nuclearity of 48 in the kernel. The phosphinous acid-phosphinito ligand set, which consists of two phosphinous acids and one phosphinito motif, has strong intramolecular hydrogen bonds; the π-π stacking interactions between the phosphorus- and sulfur-based ligands provide additional stabilization to the kernel. Highly stable Au52(HOPPh2)8(OPPh2)4(TBBT)16 serves as an effective electrocatalyst in the oxygen reduction reaction. Density functional theory calculations suggest that the phosphinous acid-phosphinito ligands provide the most active sites in the electrochemical catalysis, with O* formation being the rate-determining step.

The crystalline behavior of poly(L‐lactide) induced by nucleating agents with amide structure: The effect of benzamide molecule symmetry

AbstractAmide nucleating agents have been reported to be effective in promoting poly(L‐lactide) (PLLA) crystallization, while few research efforts have focused on the structure–activity relationship of the nucleating agents which is one basic issue to develop new agents. In this work, three amide nucleating agents with different symmetry were designed and synthesized to investigate the effect of the symmetry of benzamide nucleating agents on PLLA crystallization. It is found that the C3 symmetric amide structure of N, N′, N″‐tricyclohexyl‐1,3,5‐benzenetriamine (BTCA) agent can form a highly oriented structure by a triple hydrogen bond of π–π bond and benzene ring and can act as efficient nucleation sites. In addition, the strong intramolecular hydrogen bond with PLLA would further promote the crystallization of PLLA. In general, it is the self‐assembled ability and intramolecular hydrogen bonding with PLLA affects the rate and degree of PLLA crystallinity, and we find the C3 symmetric amide structure exhibits the best performance.

Design and synthesis of biodegradable nonconjugated S[sbnd]S[sbnd]PAMAM dendrimers with unexpected Deep-red/NIR emission and cell membrane targeting ability for biological imaging

Fluorescent non-conjugated polymers without any π-aromatic building blocks are of great significance in biological applications due to low cytotoxicity and good biocompatibility. However, it is still a great challenge to achieve bright and deep-red/near-infrared (NIR) emissions. Herein, we have designed and synthesized a series of deep-red/NIR non-conjugated polymers with aggregation-induced emission based on disulfide-linked poly(amidoamine) (SSPAMAM) dendrimers, which exhibit excellent biodegradation for bioimaging. These SSPAMAM dendrimers (G0.5-G2.0) containing disulfide bonds in their backbone were synthesized in high yield by incorporating cystamine instead of common diacrylamide. Unexpectedly, the SSPAMAM dendrimers prepared exhibited bright and excitation dependent multicolor-tunable emission. More interestingly, G2.0 SSPAMAM showed a deep-red/NIR emission (λem = 625 nm with a shoulder at 800 nm) originated from an extraordinarily rigid and compact conformation via strong intramolecular hydrogen bonds. Meanwhile, these dendrimers displayed excellent biodegradability because of the large number of disulfide linkages in backbone. Due to the excellent specific cytomembrane location, SSPAMAM dendrimers can be used as a potential cell membrane imaging reagent for multi-color (blue, green, and deep-red) imaging. Furthermore, they could also be used in zebrafish for bioimaging. This investigation has expanded the applications of fluorescent non-conjugated polymers to the field of long-wavelength in vivo biological imaging.

Vibrational Dynamics of the Intramolecular H-Bond in Acetylacetone Investigated with Transient and 2D IR Spectroscopy.

Acetylacetone (AcAc) has proven to be a fruitful but highly challenging model system for the experimental and computational interrogation of strong intramolecular hydrogen bonds. Key questions remain, however, regarding the identity of the minimum-energy structure of AcAc and the dynamics of intramolecular proton transfer. Here, we investigate the OH/OD stretch and bend regions of the enol tautomer of AcAc and its deuterated isotopologue with transient absorption and 2D IR spectroscopy. The OH bend region reveals a single dominant diagonal transition near 1625 cm-1 with intense cross peaks to lower-frequency modes, demonstrating highly mixed fingerprint transitions that contain OH bend character. The anharmonic coupling of the OH bend results in a highly elongated OH bend excited-state absorption transition that indicates a large manifold of OH bend overtone/combination bands in the OH stretch region that leads to strong bend-stretch Fermi resonance interactions. The OH and OD stretch regions consist of broad ground-state bleach signals, but there is no clear evidence of ω21 excited-state absorptions due to rapid population relaxation arising from strong intramolecular coupling to bending, fingerprint, and low-frequency H-bond modes. Orientational relaxation dynamics persist for timescales longer than the vibrational lifetimes, with polarization anisotropy components decaying within approximately 2 and 10 periods of the O-O oscillation for the OH and OD stretch, respectively. The significant isotopic dependence of the orientational dynamics is discussed in the context of intramolecular mode coupling, diffusional processes, and contributions from proton/deuteron transfer dynamics.

Oxalamide-Bridged Ferrocenes: Conformational and Gelation Properties and In Vitro Antitumor Activity

The N-termini of the constitutional isomeric ferrocene peptides Boc–NH–Fn–CO–Ala–OMe (1) and Boc–Ala–NH–Fn–COOMe (2) were deprotected in the acidic milieu and subjected to oxalyl chloride-mediated dimerization to afford the oxalamides −(CO–NH–Fn–CO–Ala–OMe)2 (3) and −(CO–Ala–NH–Fn–COOMe)2 (4), respectively. The goal compounds were evaluated for their conformational properties, toluene gelation ability, and effect on cell viability of tumor (HeLa, MCF7, HepG2) and normal (HEK293T) cell lines. Detailed spectroscopic analysis in solution revealed the different conformational behavior of constitutional isomers 3 and 4, and oxalamide 3 was found to have a higher degree of chiral organization due to its involvement in stronger intramolecular hydrogen bonds. Crystallographic analysis showed the presence of two symmetry-independent conformers of compound 3 stabilized by stronger intramolecular hydrogen bonds. The tested compounds self-assemble in toluene to provide supramolecular nanostructures but were unable to form a stable gel. Interestingly, the formation of a stable gel was observed when the toluene solution of 4 was sonicated. Cytotoxic evaluation of 3 and 4 revealed a weaker growth-inhibitory effect on tumor cell lines compared to cisplatin. Oxalamide 3 appeared to be more cytotoxic to HeLa and MCF7 cancer cell lines than to normal HEK293T cells, indicating its potential for drug development as an anticancer agent.

Near-Infrared Light-Boosted Photodynamic-Immunotherapy based on sulfonated Metal-Organic framework nanospindle

Photoactive metal–organic frameworks have achieved great success in the photodynamic therapy (PDT). However, poor therapeutic effect under near-infrared (NIR) irradiation becomes a big changllege for the fully eradication of tumors by using photodynamic MOFs. Herein, a spindle-shaped PCN-222-SO3H (PCN-SU) with the enhanced NIR absorption was synthesized by the sulfonating reaction. After sulfonation, the strong intramolecular hydrogen bonds between the introduced sulfonic anions and TCPP ligands could induce the distortion of porphyrin rings. This distortion leads to the lower energy gap of HOMO and LOMO, thereby increasing the absorption in the near-infrared region. Comparing with PCN-222, great improvements of photoactive performances in PCN-SU result in the boosting generation of singlet oxygen under NIR irradiation. Furthermore, PCN-SU gives high efficiency to trigger the immunogenic cell death (ICD) and also to stimulate the maturation of dendritic cells than that of prototype PCN-222. The combination of immune checkpoint inhibitors (anti-PD-1) with the photodynamic PCN-SU largely enhances the infiltration of cytotoxic T cells in the tumor site under NIR irradiation, and thus to obtain the tumor suppression of 99.6 % in vivo. This new sulfonating strategy provides a new idea for enhancing the photoactivity of the porphyrin-based delivery system, which is beneficial to the improvement of PDT and related combined treatments.

Understanding the abundance of the rare sugar β-D-allose.

The conformational landscape of β-D-allose, a rare sugar, was investigated using laser ablation in combination with high-resolution rotational spectroscopy. Altogether, three species are identified, exhibiting a counter-clockwise intramolecular hydrogen bond network. The effect of epimerization on the main aldohexose is also studied and, despite the main conformers being very similar, the position of the hydroxyl groups in allose allows the formation of considerably stronger intramolecular hydrogen bonds than in glucose, and this could explain the low abundance of β-D-allose in Nature.

On-the-fly adiabatically switched semiclassical initial value representation molecular dynamics for vibrational spectroscopy of biomolecules.

Semiclassical (SC) vibrational spectroscopy is a technique capable of reproducing quantum effects (such as zero-pointenergies, quantum resonances, and anharmonic overtones) from classical dynamics runs even in the case of very large dimensional systems. In a previous study [Conte et al. J. Chem. Phys. 151, 214107 (2019)], a preliminary sampling based on adiabatic switching has been shown to be able to improve the precision and accuracy of semiclassical results for challenging model potentials and small molecular systems. In this paper, we investigate the possibility to extend the technique to larger (bio)molecular systems whose dynamics must be integrated by means of ab initio "on-the-fly" calculations. After some preliminary tests on small molecules, we obtain the vibrational frequencies of glycine improving on pre-existing SC calculations. Finally, the new approach is applied to 17-atom proline, an amino acid characterized by a strong intramolecular hydrogen bond.

Brightening up Circularly Polarized Luminescence of Monosubstituted Polyacetylene by Conformation Control: Mechanism, Switching, and Sensing.

The first example of luminescent monosubstituted polyacetylenes (mono-PAs) is presented, based on a contracted cis-cisoid polyene backbone. It has an excellent circularly polarized luminescence (CPL) performance with a high dissymmetric factor (up to the order of 10-1 ). The luminescence stems from the helical cis-cisoid PA backbone, which is tightly fixed by the strong intramolecular hydrogen bonds, thereby reversing the energy order of excited states and enabling an emissive energy dissipation. CPL switches are facilely achieved by the solvent and temperature through reversible conformational transition. By taking advantages of fast response and high sensitivity, the thin film of mono-PAs could be used as a CPL-based probe for quantitative detection of trifluoroacetic acid with a wider linear dynamic range than those of photoluminescence and circular dichroism. This work opens a new avenue to develop novel smart CPL materials through modulating conformational transition.

Brightening up Circularly Polarized Luminescence of Monosubstituted Polyacetylene by Conformation Control: Mechanism, Switching, and Sensing

AbstractThe first example of luminescent monosubstituted polyacetylenes (mono‐PAs) is presented, based on a contracted cis‐cisoid polyene backbone. It has an excellent circularly polarized luminescence (CPL) performance with a high dissymmetric factor (up to the order of 10−1). The luminescence stems from the helical cis‐cisoid PA backbone, which is tightly fixed by the strong intramolecular hydrogen bonds, thereby reversing the energy order of excited states and enabling an emissive energy dissipation. CPL switches are facilely achieved by the solvent and temperature through reversible conformational transition. By taking advantages of fast response and high sensitivity, the thin film of mono‐PAs could be used as a CPL‐based probe for quantitative detection of trifluoroacetic acid with a wider linear dynamic range than those of photoluminescence and circular dichroism. This work opens a new avenue to develop novel smart CPL materials through modulating conformational transition.

Quantum-chemical study on the relative stability of sildenafil tautomers

The tautomeric equilibrium of sildenafil molecule was theoretically studied using B3LYP and M06-2X density functional theory (DFT) methods in connection with aug-cc-pVDZ correlation consistent basis set. Calculations were performed for gas phase and water solution conditions modelled by polarizable continuum model (PCM). Three tautomeric forms are possible. Two keto forms: A — where the tautomeric proton in more distant from carbonyl group and B — where it is closer, and one enol form denoted, C. Both DFT methods qualitatively give similar tautomer stability order: B > A > C. The B tautomer is dominant in gas phase and water environment, whereas the C tautomer is too high in energy to be present in the tautomeric mixture. Regarding the A tautomer, it is not present in the gas phase but is present in small amounts in water solution. According to B3LYP/aug-cc-pVDZ, the relative Gibbs-free energies for A and C relative to B are 10.05 kcal/mol and 11.91 kcal/mol for gas phase and 5.49 kcal/mol and 12.49 kcal/mol for water solution. According to M06-2X/aug-cc-pVDZ, the relative Gibbs-free energies for A and C are 9.12 kcal/mol and 10.60 kcal/mol for gas phase and 4.27 kcal/mol and 10.23 kcal/mol for water solution. Therefore, for in vivo conditions, we expect that the B tautomer is dominant, and there may exist small amounts of the A tautomer. The C enol tautomer is not present at all. This picture is very different from the parent tautomeric system: 4-hydroxypyrimidine/4-pyrimidinone where the C enol tautomer is less stable than keto B only by about 1 kcal/mol in the gas phase and the A keto tautomer is the least stable and not present in the tautomeric mixture. In order to understand these differences, we performed additional calculations for a series of parent molecules starting from 4-hydroxypyrimidine/4-pyrimidinone, going through two in-between model molecules and ending at Sildenafil molecule. We found that the most important reasons of C form destabilization are dearomatization of the 6-membered ring caused by the fusion with pyrazole ring, lack of strong intramolecular hydrogen bond in C form of sildenafil and presence of destabilizing steric interaction of oxygen and nitrogen atoms of two 6-memberd rings in this tautomer.

Unusual Para-Substituent Effects on the Intramolecular Hydrogen Bond in Hydrazone-Based Switches: Insights from Chemical Landscape Analysis and DFT Calculations

Тhe adequacy of chemical property predictions strongly depends on the structure representation, including the proper treatment of the tautomeric and isomeric forms. A combination of an in-house developed open-source tool for automatic generation of tautomers, Ambit-Tautomer, based on H-atom shift rules and standard quantum chemical (DFT) calculations is used for a detailed investigation of the possible geometric isomers, conformers and tautomers of unsubstituted and para-substituted phenylhydrazones, systems with experimentally observed unusual para-substituent effects on the intramolecular hydrogen bond (IMHB) for E-isomers of the compounds. The computational results show that the energetically preferred E-isomers are characterized by stronger IMHBs than the corresponding Z-isomers. The HN–N=C–C=N molecular fragment in the E-configurations is less sensitive to the substitution effect than the HN–N=C–C=O fragment in the isomers with Z-configuration. A probable reason for this decreased sensitivity of E-isomers to phenyl ring substitution is the more efficient conjugation and charge distribution in the HN–N=C–C=N fragment.

Analytical Gradients for Nuclear-Electronic Orbital Time-Dependent Density Functional Theory: Excited-State Geometry Optimizations and Adiabatic Excitation Energies.

The computational investigation of photochemical processes often entails the calculation of excited-state geometries, energies, and energy gradients. The nuclear-electronic orbital (NEO) approach treats specified nuclei, typically protons, quantum mechanically on the same level as the electrons, thereby including the associated nuclear quantum effects and non-Born-Oppenheimer behavior into quantum chemistry calculations. The multicomponent density functional theory (NEO-DFT) and time-dependent DFT (NEO-TDDFT) methods allow efficient calculations of ground and excited states, respectively. Herein, the analytical gradients are derived and implemented for the NEO-TDDFT method and the associated Tamm-Dancoff approximation (NEO-TDA). The programmable equations for these analytical gradients as well as the NEO-DFT analytical Hessian are provided. The NEO approach includes the anharmonic zero-point energy (ZPE) and density delocalization associated with the quantum protons as well as vibronic mixing in geometry optimizations and energy calculations of ground and excited states. The harmonic ZPE associated with the other nuclei can be computed via the NEO Hessian. This approach is used to compute the 0-0 adiabatic excitation energies for a set of nine small molecules with all protons quantized, exhibiting slight improvement over the conventional electronic approach. Geometry optimizations of two excited-state intramolecular proton-transfer systems, [2,2'-bipyridyl]-3-ol and [2,2'-bipyridyl]-3,3'-diol, are performed with one and two quantized protons, respectively. The NEO calculations for these systems produce electronically excited-state geometries with stronger intramolecular hydrogen bonds and similar relative stabilities compared to conventional electronic methods. This work provides the foundation for nonadiabatic dynamics simulations of fundamental processes such as photoinduced proton transfer and proton-coupled electron transfer.

DFT study of the radical scavenging activity of isoxanthohumol, humulones (α-acids), and iso-α-acids from beer

Humulones and iso-humulones are potent natural antioxidants found in beer. In this study, density functional theory (DFT) method was applied for elucidating the structure-antioxidant activity relationship and molecular mechanism of antioxidant activity of eight bioactive humulones previously identified in different beer samples: isoxanthohumol, (R)- and (S)-adhumulone, cis- and trans-iso-adhumulone, cis- and trans-iso-n-humulone, and desdimethyl-octahydro-iso-cohumulone. The calculated bond dissociation enthalpies (BDEs) suggest that desdimethyl-octahydro-iso-cohumulone was the most potent compound with BDEs 5.1 and 23.9 kJ/mol lower compared to the values for resveratrol in gas phase and water, respectively. The enolic –OH is the most reactive site for hydrogen atom transfer (HAT). The presence of β-keto group with respect to enolic –OH diminishes the HAT potency via the formation of a strong intramolecular hydrogen bond. Another common antioxidant mechanism, single electron transfer followed by proton transfer (SET-PT), is only feasible for isoxanthohumol. The results of this study indicate a strong correlation between the increased antioxidant activity of beer products and the higher content of reduced iso-α-acids.

Energetic compounds based on a new fused triazolo[4,5-d]pyridazine ring: Nitroimino lights up energetic performance

The difference between nitroimino and nitroamino in compound 5. • A new triazolo[4,5–d]pyridazine fused ring was synthesized. • A different method was found to synthesize the pyridazine fused ring. • The nitroimino group has a low ESP and forms strong HB and π-π interactions. • The properties of compounds 7 and 8 are comparable to those of HMX. • The synthesis of 5 is cost effective and can be extended to gram-scale (2 g). A series of highly energetic materials with good detonation performance, high density and low impact sensitivity based on a new triazolo[4,5–d]pyridazine fused ring was synthesized and characterized. 4-Nitroamino-7-nitroimino-triazolo[4,5–d]pyridazine ( 5 ) was characterized by single crystal X-ray structure analysis, which shows that the proton of one nitroamino group was transferred to the pyridazine ring forming a nitroimino moiety. The electrostatic potential (ESP) of 5 shows the nitroimino group has the lowest negative value, while the nitroamino area has a high positive value. The analysis of NCI plots indicates strong intramolecular hydrogen bonds (HB) and π-π interactions which arise from the newly formed nitroimino group. This supports that the rearrangement of the nitroamino group to form the nitroimino moiety lowers the impact sensitivity. Compound 5 ·H 2 O exhibits face-to-face packing, which gives rise to a relatively high density of 1.87 g cm −3 and a low impact sensitivity of 18 J. Its hydrazinium and hydroxylammonium salts have high detonation velocities of 9351 m s −1 and 9307 m s −1 , respectively. Their impact and friction sensitivities (7 J, 120 N and 8 J, 160 N) are similar to HMX. This proclivity for rearrangement by a nitroamino group provides new insight into the design of next generation high energy density materials.

Photophysical studies of organostannoxane supported hexafluorophore assemblies

The condensation reaction between n-butylstannoic acid and ArCOOH (Ar = 1-naphthyl-CH2 (1), 9-anthracenyl (2), 9-xanthenyl (3), 1-pyrenyl-(CH2)3 (4), 1-pyrenyl (5)) afforded hexameric organostannoxanes [n-BuSn(O)(O2CAr)]6 in high yield. The molecular structures of compounds 2 and 3 were confirmed by single crystal X-ray diffraction analysis. These compounds possess a drum-like structure and each molecule is attached with six fluorophores through carboxylate functionality. 119Sn NMR and MALDI-TOF analyses suggest that the compounds 1, 4, and 5 also belong to the family of organotin drum structure. There are also various intra- and intermolecular interaction between the fluorophores. In particular, compound 2 shows a strong intramolecular hydrogen bond (CH····π 2.489 Å) between two anthracene moieties. However, such interaction is weaker in 3. The absorption spectra of 1–5 indicate that λmax was very slightly red-shifted with respect to their fluorophore carboxylic acid. Fluorescence measurements reveal that these molecules are good blue emitters in solution state but red-shifted in the solid-state. Quantum yield calculation shows that emission efficiencies decreased for smaller spacers between fluorophore and stannoxane core. We have carried out thermal studies for all compounds. These suggest that the compounds are robust and stable until about 300 °C. Interestingly, we have demonstrated the synthesis of SnO2 from the hexameric organotin drum 3 by heating in the temperature range 600–1200 °C.

Maleate salts of bedaquiline.

Bedaquiline is one of two important new drugs for the treatment of drug-resistant tuberculosis (TB). It is marketed in the US as its fumarate salt, but only a few salts of bedaquiline have been structurally described so far. We present here five crystal structures of bedaquilinium maleate {systematic name: [4-(6-bromo-2-meth-oxy-quinolin-3-yl)-3-hy-droxy-3-(naphthalen-1-yl)-4-phenyl-but-yl]di-methyl-aza-nium 3-carb-oxy-prop-2-enoate}, C32H32BrN2O2 +·C4H3O4 -, namely, a hemihydrate, a tetra-hydro-furan (THF) solvate, a mixed acetone/hexane solvate, an ethyl acetate solvate, and a solvate-free structure obtained from the acetone/hexane solvate by in situ single-crystal-to-single-crystal desolvation. All salts exhibit a 1:1 cation-to-anion ratio, with the anion present as monoanionic hydro-maleate and a singly protonated bedaquilinium cation. The maleate exhibits the strong intra-molecular hydrogen bond typical for cis-di-carb-oxy-lic acid anions. The conformations of the cations and packing inter-actions in the maleate salts are compared to those of free base bedaquiline and other bedaquilinium salts.

Naphthalenediimides with High Fluorescence Quantum Yield: Bright-Red, Stable, and Responsive Fluorescent Dyes.

The naphthalenediimide (NDI) scaffold in contrast to its higher congeners possess low-fluorescence. In spite of elegant synthetic developments, a highly emissive NDI is quite rare to find, as well as, a green-light-emitting NDI is yet to be explored. Herein, we report a novel class of symmetric and asymmetric NH2 -substituted core-NDIs (1-5) with tunable fluorescence in the visible region and extending to the NIR frontier. Importantly, the bis-NH2 -substituted NDI 2 revealed quantum yield, of ≈81 and ≈68 % in toluene and DMSO, respectively, suggesting versatility of the fluorophore in a wide range of solvent polarity. The dye 1 is shown to be the first NDI-based green-light emitter. The donor piperidine group in 5 diminish the by 40-fold providing a lever to modulate the excited-state intramolecular proton transfer (ESIPT) process. Our synthetic protocol applies a Pd catalyst and a benign hydride source simplifying the non-trivial -NH2 group integration at the NDI-core. TD-DFT calculations predicted strong intramolecular hydrogen bonds in the excited state in the bulk nonpolar medium and responsiveness to solvent polarity. The maximization of the NDI emission outlined here would further boost the burgeoning repertoire of applications of the NDI scaffold.

Catalytic Conversion of Sugar-Derived Polyhydroxy Acid to Trimellitate

Biomass resources, especially carbohydrates derived from cellulose and hemicellulose, could be utilized as an alternative feedstock for the production of fuel and bulk chemicals. Here, we present a sustainable route for the synthesis of trimethyl trimellitate from 1,6-dimethyl galactarate, the diester of sugar-derived polyhydroxy galactaric acid. The process starts with the deoxydehydration reaction of 1,6-dimethyl galactarate to form dimethyl muconate with an 84% yield. Nuclear magnetic resonance (NMR) and density functional theory results show that the molecular structure of 1,6-dimethyl galactarate possesses strong intramolecular hydrogen bond networks and is endowed with chemical recalcitrance. ¹H NMR tests of variable catalyst concentrations reveal that the introduction of ammonium perrhenate could weaken the intramolecular hydrogen bond effect and activate the chemically inert molecules. The Diels–Alder reaction of muconate and acrylate is conducted efficiently to produce a substituted cyclohexene intermediate without any catalyst used, and a 72% yield of the target product, trimethyl trimellitate, is obtained via the dehydro-aromatization reaction of the cycloadduct. This new approach provides a template path for the synthesis of aromatic oxygenated compounds and would promote the development of green polymer materials.