Boron catalysis in a designer enzyme.

Enzymes play an increasingly important role in improving the benignity and efficiency of chemical production, yet the diversity of their applications lags heavily behind chemical catalysts as a result of the relatively narrow range of reaction mechanisms of enzymes. The creation of enzymes containing non-biological functionalities facilitates reaction mechanisms outside nature's canon and paves the way towards fully programmable biocatalysis1-3. Here we present a completely genetically encoded boronic-acid-containing designer enzyme with organocatalytic reactivity not achievable with natural or engineered biocatalysts4,5. This boron enzyme catalyses the kinetic resolution of hydroxyketones by oxime formation, in which crucial interactions with the protein scaffold assist in the catalysis. A directed evolution campaign led to a variant with natural-enzyme-like enantioselectivities for several different substrates. The unique activation mode of the boron enzyme was confirmed using X-ray crystallography, high-resolution mass spectrometry (HRMS) and 11B NMR spectroscopy. Our study demonstrates that genetic-code expansion can be used to create evolvable enantioselective enzymes that rely on xenobiotic catalytic moieties such as boronic acids and access reaction mechanisms not reachable through catalytic promiscuity of natural or engineered enzymes.

3-Pyridinylboronic Acid Ameliorates Rotenone-Induced Oxidative Stress Through Nrf2 Target Genes in Zebrafish Embryos.

Parkinson's disease (PD) is one of the most common forms of neurodegenerative diseases and research on potential therapeutic agents for PD continues. Rotenone is a neurotoxin that can pass the blood-brain barrier and is used to generate PD models in experimental animals. Boron is a microelement necessary for neural activity in the brain. Antioxidant, non-cytotoxic, anti-genotoxic, anti-carcinogenic effects of boric acid, the salt compound of boron has been reported before. Boronic acids have been approved for treatment by FDA and are included in drug discovery studies and pyridine boronic acids are a subclass of heterocyclic boronic acids used in drug design and discovery as substituted pyridines based on crystal engineering principles. The aim of our study was to determine the effect of 3-pyridinylboronic acid in rotenone-exposed zebrafish embryos, focusing on oxidant-antioxidant parameters and gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes gclm, gclc, hmox1a, nqo1, and PD related genes, brain-derived neurotrophic factor, dj1, and tnfα. Zebrafish embryos were exposed to Rotenone (10 µg/l); Low Dose 3-Pyridinylboronic acid (100 µM); High Dose 3-Pyridinylboronic acid (200 µM); Rotenone + Low Dose-3-Pyridinylboronic acid (10 µg/l + 100 µM); Rotenone + High Dose-3-Pyridinylboronic acid (10 µg/l + 200 µM) in well plates for 96 h post-fertilization (hpf). Our study showed for the first time that 3-pyridinylboronic acid, as a novel sub-class of the heterocyclic boronic acid compound, improved locomotor activities, ameliorated oxidant-antioxidant status by decreasing LPO and NO levels, and normalized the expressions of bdnf, dj1, tnf⍺ and Nrf2 target genes hmox1a and nqo1 in rotenone exposed zebrafish embryos. On the other hand, it caused the deterioration of the oxidant-antioxidant balance in the control group through increased lipid peroxidation, nitric oxide levels, and decreased antioxidant enzymes. We believe that these results should be interpreted in the context of the dose-toxicity and benefit-harm relationship of the effects of 3-pyridinylboronic.

3-Pyridinylboronic acid normalizes the effects of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure in zebrafish embryos.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that damages dopaminergic neurons. Zebrafish has been shown to be a suitable model organism to investigate the molecular pathways in the pathogenesis of Parkinson's disease and also for potential therapeutic agent research. Boron has been shown to play an important role in the neural activity of the brain. Boronic acids are used in combinatorial approaches in drug design and discovery. The effect of 3-pyridinylboronic acid which is an important sub-class of heterocyclic boronic acids has not been evaluated in case of MPTP exposure in zebrafish embryos. Accordingly, this study was designed to investigate the effects of 3-pyridinylboronic acid on MPTP exposed zebrafish embryos focusing on the molecular pathways related to neurodegeneration and apoptosis by RT-PCR. Zebrafish embryos were exposed to MPTP (800 µM); MPTP + Low Dose 3-Pyridinylboronic acid (50 µM) (MPTP + LB) and MPTP + High Dose 3-Pyridinylboronic acid (100 µM) (MPTP + HB) in well plates for 72 hours post fertilization. Results of our study showed that MPTP induced a P53 dependent and Bax mediated apoptosis in zebrafish embryos and 3-pyridinylboronic acid restored the locomotor activity and gene expressions related to mitochondrial dysfunction and oxidative stress due to the deleterious effects of MPTP, in a dose-dependent manner.

Phenylboronic Acid Modification Augments the Lysosome Escape and Antitumor Efficacy of a Cylindrical Polymer Brush-Based Prodrug.

Timely lysosome escape is of paramount importance for endocytosed nanomedicines to avoid premature degradation under the acidic and hydrolytic conditions in lysosomes. Herein, we report an exciting finding that phenylboronic acid (PBA) modification can greatly facilitate the lysosome escape of cylindrical polymer brushes (CPBs). On the basis of our experimental results, we speculate that the mechanism is associated with the specific interactions of the PBA groups with lysosomal membrane proteins and hot shock proteins. The featured advantage of the PBA modification over the known lysosome escape strategies is that it does not cause significant adverse effects on the properties of the CPBs; on the contrary, it enhances remarkably their tumor accumulation and penetration. Furthermore, doxorubicin was conjugated to the PBA-modified CPBs with a drug loading content larger than 20%. This CPBs-based prodrug could eradicate the tumors established in mice by multiple intravenous administrations. This work provides a novel strategy for facilitating the lysosome escape of nanomaterials and demonstrates that PBA modification is an effective way to improve the overall properties of nanomedicines including the tumor therapeutic efficacy.

Tannic acid-directed synthesis of magnetic and boronic acid-functionalized metal-organic frameworks for selective extraction and quantification of catecholamines in human urine.

A novel magnetic borate-functionalized metal-organic framework nanocomposite was designed and fabricated for selective enrichment of catecholamines from human urine. Firstly, the polytannic acid (PTA) layer with natural low-cost and ecofriendly polyphenol tannic acid as the organic ligand and Fe3+ as the cross-linker was coated onto the surface of Fe3O4. Then, the borate-functionalized metal-organic framework (MIL-100(Fe)-B) with 5-boronobenzene-1,3-dicarboxylic acid as a ligand fragment was modified onto the PTA-coated Fe3O4 through a metal-ligand-fragment coassembly strategy. The obtained smart porous adsorbent Fe3O4@PTA@MIL-100(Fe)-B was confirmed by means of several characterization methods and then applied as an effective magnetic solid phase extraction (MSPE) sorbent for specific extraction of trace catecholamines in human urine. The Plackett-Burman design was used for screening the variables significantly affecting the extraction efficiency. Then, the significant factors were further investigated by the Box-Behnken design to determine the optimal extraction conditions. Under the optimal conditions, a method for selective MSPE combined with high-performance liquid chromatography with a fluorescence detector for the quantitation of catecholamines in human urine was developed and validated. With the proposed method, the linearity range was from 0.500 to 500 ng mL-1 for norepinephrine and epinephrine and from 1.00 to 500 ng mL-1 for dopamine. The detection limits were 0.050, 0.11, and 0.20 ng mL-1 for norepinephrine, epinephrine, and dopamine, respectively. The recoveries from spiking experiments varied from 91.5 to 108% with relative standard deviations (RSDs) of 0.80-4.8%. The established method is rapid, sensitive, accurate, inexpensive, and ecofriendly and was successfully applied to the determination of the target catecholamines in human urine samples.

The Chemistry of Boronic Acids in Nanomaterials for Drug Delivery.

Interest in increasing drug delivery efficiency has risen over the past decade both as a means to improve efficacy of already clinically available drugs and due to the increased difficulties of approving new drugs. As a functional group for targeted drug delivery, boronic acids (BAs) have been incorporated in polymeric particles both as a stimuli-responsive functional group and as a targeting ligand. Here, BA chemistry presents a wealth of opportunities for biological applications. It not only reacts with several chemical markers of disease such as reactive oxygen species (ROS), adenosine triphosphate (ATP), glucose, and reduced pH, but it also acts as ligands for diols such as sialic acid. These stimuli-responsive drug delivery systems optimize delivery of therapeutics based on rational design and precise molecular engineering. When designing materials containing BA, the unique chemical properties are important to take into consideration such as its vacant p-orbital, its molecular geometry, and the designed acid's pKa. Instead of behaving as most carboxylic acids that donate protons, BAs instead primarily act as Lewis acids that accept electrons. In aqueous solution, most polymers containing BA exist in an equilibrium between their triangular hydrophobic form and a tetrahedral hydrophilic form. The most common pKa's are in the nonphysiological range of 8-10, and much ongoing research focuses on modifying BAs into materials sensitive to a more physiologically relevant pH range. So far, BA moieties have been incorporated into a stunning array of materials, ranging from small molecules that can self-assemble into higher order structures such as micelles and polymeric micelles, via larger polymeric assemblies, to large scale hydrogels. With the abundance of biological molecules containing diols and polyhydroxy motifs, BA-containing materials have proven valuable in several biomedical applications such as treatment of cancer, diabetes, obesity, and bacterial infections. Both materials functionalized with BA and boronic esters display good safety profiles in vitro and in vivo; thus, BA-containing materials represent promising carriers for responsive delivery systems with great potential for clinical translation. The intention of this Account is to showcase the versatility of BA for biomedical applications. We first discuss the chemistry of BA and what to consider when designing BA-containing materials. Further, we review how its chemistry recently has been applied to nanomaterials for enhanced delivery efficiency, both as a stimuli-responsive group and as a targeting ligand. Lastly, we discuss the current limitations and further perspectives of BA in biomaterials, based on the great benefits that can come from utilizing the unique BA chemistry to enhance drug delivery efficiency.

Serendipitous discovery of aryl boronic acids as ß-lactamase inhibitors.

High throughput screening for ß-lactamase inhibitors afforded biphenyl hits such as 1. Hit confirmation and X-ray soaking experiments with Pseudomonas Aeruginosa AmpC enzyme led to the identification of an aryl boronic acid-serine complex 4, which was formed from phenyl boronic acid 8 (an impurity in compound 1) and ethylene glycol (the cryoprotectant in the soaking experiment).

Development of a bioavailable boron-containing PI-103 Bioisostere, PI-103BE.

PI-103 (7) is a potent dual phosphatidylinositol 3-kinase (PI3K)/mTOR inhibitor, but its rapid in vivo metabolism hinders its further clinical development. To improve the bioavailability of PI-103, we designed and synthesized a PI-103 bioisostere, PI-103BE (9) in which the phenolic hydroxyl group of PI-103 was replaced by a boronate, a structural modification known to enhance bioavailability of molecules containing phenolic hydroxyl moieties. In cell culture, PI-103BE is partially converted to its corresponding boronic acid (10) and to a lesser extent the active ingredient, PI-103. This mixture contributes to the in vitro activity of 9 that shows reduced potency compared to the parent compound. When administered to mice by oral gavage, 9 displays a significantly improved pharmacokinetic profile compared to PI-103, which shows no oral bioavailability at the same dose. Drug exposure of 9 as measured by the area under curve (AUC) value is 88.2 ng/mL*h for 7 and 8879.9 ng/mL*h for 10. When given by intraperitoneal injection (IP), the prodrug afforded an AUC of 32.3 ng/mL*h for 7 and 400.9 ng/mL*h for 10, compared to 9.7 ng/mL*h from PI-103 injection. In plasma from both pharmacokinetic studies, 9 is fully converted to 10 and 7, with the boronic acid metabolite (10) displaying antiproliferative activities comparable to 9, but weaker than 7. The boronic bioisostere of PI-103 thus offers an improved bioavailability that could be translated to in vivo efficacy of PI-103.

Boronic acid functionalized fibrous cellulose for the selective enrichment of glycopeptides.

Enrichment of glycoproteins has been important because of their dynamicity and role in biological systems. Study of glycoproteins is complex because of the simultaneous glycosylation and deglycosylation inside the body. Often employed affinities for glycopeptides are hydrazide, boronic acid, or physiosorbed lectin on support materials. Cellulose, a natural polysaccharide, has rich surface chemistry, stable structure, low cost and availability in different variants. In present study, fibrous cellulose is oxidized using periodate to modify with boronic acid. Attachment of boronic acid is confirmed by Fourier transform infrared spectroscopy. Particle size and morphology of boronic acid@fibrous cellulose is studied by scanning electron microscopy. The enrichment efficiency is evaluated by using horseradish peroxidase as model protein. Boronic acid@fibrous cellulose is selective up to 1:250 for spiked horseradish peroxidase in bovine serum albumin digest, sensitive down to 0.1 femtomol and recovering 88.15% glycopeptides. Moreover, protein binding capacity is determined as 213 mg/g and 41% sequence coverage of horseradish peroxidase protein with all eight glycosylation sites detected. Total of 18 glycopeptides are enriched from immunoglobulin digest showing ability of boronic acid@fibrous cellulose to enrich glycoproteins from multiglycoforms. Enrichment from human serum recovers 18% extracellular and 72% secreted glycoproteins via bottom-up approach and online tools.

The challenges of glycan recognition with natural and artificial receptors.

Glycans - simple or complex carbohydrates - play key roles as recognition determinants and modulators of numerous physiological and pathological processes. Thus, many biotechnological, diagnostic and therapeutic opportunities abound for molecular recognition entities that can bind glycans with high selectivity and affinity. This review begins with an overview of the current biologically and synthetically derived glycan-binding scaffolds that include antibodies, lectins, aptamers and boronic acid-based entities. It is followed by a more detailed discussion on various aspects of their generation, structure and recognition properties. It serves as the basis for highlighting recent key developments and technical challenges that must be overcome in order to fully deal with the specific recognition of a highly diverse and complex range of glycan structures.

Assessment of a 18F-Phenylboronic Acid Radiotracer for Imaging Boron in Maize.

Boron (B) is an essential plant micronutrient. Deficiencies of B have drastic consequences on plant development leading to crop yield losses and reductions in root and shoot growth. Understanding the molecular and cellular consequences of B deficiency is challenging, partly because of the limited availability of B imaging techniques. In this report we demonstrate the efficacy of using 4-fluorophenylboronic acid (FPBA) as a B imaging agent, which is a derivative of the B deficiency mimic phenylboronic acid (PBA). We show that radioactively labelled [18F]FPBA (t½=110 m) accumulates at the root tip, the root elongation zone and at lateral root initiation sites in maize roots, and also translocates to the shoot where it accumulates along the leaf edges. Treatment of maize seedlings using FPBA and PBA causes a shortened primary root phenotype with absence of lateral roots in a dose-dependent manner. The primary root defects can be partially rescued by the addition of boric acid indicating that PBA can be used to induce B deficiency in maize and that radioactively labelled FPBA can be used to image sites of B demand on a tissue level.

Colorimetric Sensor Array Based on Wulff-Type Boronate Functionalized AgNPs at Various pH for Bacteria Identification.

The efficient identification of bacteria is of considerable significance in clinical diagnosis. Herein, a novel colorimetric sensor array was developed for the detection and identification of bacteria based on the specific affinity and electrostatic interaction between Wulff-type 4-mercaptophenylboronic acid (MPBA)-mercaptoethylamine (MA) cofunctionalized AgNPs (MPBA-MA@AgNPs) and bacteria at various pH. In the neutral and alkaline conditions, AgNPs tended to be dispersed due to the specific affinity between cis-diol residues contained in carbohydrate-rich compositions on the bacterial cell surface and MPBA. Bacterial cells have different carbohydrate compositions on their surface. The differential binding affinity of MPBA on the surface of AgNPs to cis-diol residues of various carbohydrates resulted in a different color change of AgNPs, which could be tuned by pH. On the contrary, AgNPs tended to be aggregated due to the electrostatic interaction between positively charged MA and negatively charged bacteria under acidic conditions. Therefore, using various pH buffer solutions as the sensing elements and MPBA-MA@AgNPs as the indicator, bacteria could be differentiated from each other by their own color response patterns. Moreover, the complex bacteria mixtures could be well discriminated. The method is simple, efficient, and visual and has a potential application in pathogen diagnosis.

Exploring boar sperm sialylation during capacitation using boronic acid-functionalized beads.

Sialic acid (SA), which usually occupies the terminal position of oligosaccharide chains in mammalian spermatozoa, has important functions in fertilization. Compared with other methods, such as lectin probing, boronic acid could recognize and bind SA with a higher affinity and specificity at pH 6.9. In this study, two boronic acid carriers, 3-aminophenylboronic acid-labeled fluorescent latex (CML-APBA) and magnetic beads (CMM-APBA were applied to explore surface sialylation profile and sialoglycoproteins of the boar sperm. There are three binding sections of CML-APBA on the head of ejaculated sperm: acrosomal region, equatorial segment and the head posterior, which are the major regions undergoing sialylation. After capacitation in vitro, two major binding patterns of CML-APBA exists on sperm head. On some spermatozoa, sialylation exists on the equatorial segment and the posterior head, whilst on other spermatozoa, sialylation occurs on the acrosomal region and equatorial segment. Flow cytometry analysis suggested that the level of sialylation on boar sperm membrane decreases after capacitation. Furthermore, using CMM-APBA, we pulled down sialylated proteins from spermatozoa. Among them, two decapacitation factors associating on sperm surface, AWN and PSP-1, were identified. The levels of the two proteins reduced during capacitation, which might contribute to the decrease of sialylation on boar sperm surface.

Supramolecular Hydrogel Derived from a C3-Symmetric Boronic Acid Derivative for Stimuli-Responsive Release of Insulin and Doxorubicin.

A C3-symmetric triazine based triboronic acid (HG1) was designed and synthesized. HG1 was found to give hydrogel in DMSO-water (1:9). The hydrogel was rheo-reversible and thermoreversible over a few cycles. Single-crystal X-ray diffraction (SXRD) studies on the crystals of HG1 established the presence of honeycomb network in which solvent molecules (DMSO and water) were occluded. SXRD data corroborated well with the hypothesis based on which HG1 was designed. Stimuli responsive release (in vitro) of insulin and doxorubicin from the hydrogel was also achieved.

Rationalizing and advancing the 3-MPBA SERS sandwich assay for rapid detection of bacteria in environmental and food matrices.

Bacterial foodborne illness continues to be a pressing issue in our food supply. Rapid detection methods are needed for perishable foods due to their short shelf lives and significant contribution to foodborne illness. Previously, a sensitive and reliable surface-enhanced Raman spectroscopy (SERS) sandwich assay based on 3-mercaptophenylboronic acid (3-MBPA) as a capturer and indicator molecule was developed for rapid bacteria detection. In this study, we explored the advantages and constraints of this assay over the conventional aerobic plate count (APC) method and further developed methods for detection in real environmental and food matrices. The SERS sandwich assay was able to detect environmental bacteria in pond water and on spinach leaves at higher levels than the APC method. In addition, the SERS assay appeared to have higher sensitivity to quantify bacteria in the stationary phase. On the other hand, the APC method was more sensitive to cell viability. Finally, a method to detect bacteria in a challenging high-sugar juice matrix was developed to enhance bacteria capture. This study advanced the SERS technique for real applications in environment and food matrices.

Novel Approach for 99mTc-Labeling of Red Blood Cells: Evaluation of 99mTc-4SAboroxime as a Blood Pool Imaging Agent.

Angiography with radiolabeled red blood cells (RBCs) plays an important role in diagnosis and prognosis in vascular diseases. Both in vitro and in vivo methods have been developed for 99mTc-labeling of RBCs. However, these methods are complicated and lack reproducibility. Therefore, it is highly desirable to develop an alternative method for routine 99mTc-labeling of RBCs. In this report, we present a novel approach for 99mTc-labeling of RBCs. We prepared a new 99mTc(III) radiotracer [99mTcCl(CDO)(CDOH)2B-4AS] (99mTc-4ASboroxime: 4AS-B(OH)2 = 4-aminosulfonylphenyl)boronic acid, and CDOH2 = cyclohexanedione dioxime) in >95% radiochemical purity. Imaging and biodistribution studies were performed in Sprague-Dawley (SD) rats. It was found that the blood radioactivity was ∼6.0%ID/g (∼90% injected dose for 200-225 g SD rats) for 99mTc-4ASboroxime with low uptake in the myocardium, kidneys, liver, lungs, and muscle, most likely due to lack of leakage of 99mTc-labeled RBCs from the intravascular space. The blood radioactivity was almost unchanged over the 2 h period, suggesting that the binding of 99mTc-4ASboroxime to blood components (cells, proteins, and plasma) is stable. The results from γ-counting of the isolated blood components showed that 99mTc-4ASboroxime had >95% of blood radioactivity binding to RBCs, ∼1% to albumin, and ∼3% remaining free in blood plasma, demonstrating its RBC-specificity. The results from imaging studies in SD rats indicated that 99mTc-4ASboroxime is predominantly distributed in the blood pool. Main blood vessels were well delineated in the head/neck and abdominal regions. This statement was further substantiated by the results from imaging studies in pigs. 99mTc-4ASboroxime is an excellent blood pool agent with the potential for diagnosis and prognosis of vascular diseases.

Revisiting Boronate/Diol Complexation as a Double Stimulus-Responsive Bioconjugation.

This study presents a quantitative assessment of the complexation between boronic acids and diols as a reversible and double-stimulus (oxidation and acidification)-responsive bioconjugation reaction. First, by using a competition assay, we have evaluated the equilibrium constants (water, pH 7.4) of 34 boronate/diol pairs, using diols of both aliphatic and aromatic (catechols) nature; in general, catechols were characterized by constants 3 orders of magnitude higher than those of aliphatic diols. Second, we have demonstrated that successful complexation with diols generated in situ via enzymatic reactions, and the boronate complexation was also employed to calculate the Michaelis-Menten parameters for two catechol-producing reactions: the demethylation of 3-methoxytyramine and the 2-hydroxylation of estradiol, respectively, mediated by P4502D6 and P4501A2. Third, we have prepared phenylboronic acid-functionalized hyaluronic acid (HA) and demonstrated the pH and H2O2-responsive character of the adducts that it formed with Alizarin Red S (ARS) used as a model catechol. The versatility and selectivity of the complexation and the mild character of the chemical species involved therefore make the boronate/catechol reaction an interesting candidate for bioconjugation purposes.

Triazole-linked fluorescent bisboronic acid capable of selective recognition of the Lewis Y antigen.

Cell surface carbohydrates of the Lewis blood group antigens, Lewis X (Lex), Lewis Y (Ley), Lewis A (Lea), and their sialylated derivatives, such as sialy Lewis X (sLex) and sialy Lewis A (sLea), play important roles in various recognition processes. These cell surface carbohydrates have also been associated with the development and progression of many types of cancers. Recently, we synthesized four anthracene-based fluorescent bisboronic acid sensors (compounds 2a-d) linked by 'click' chemistry with tethers of different lengths to match the epitope of various Lewis group of sugars. Among the four compounds, 2a appears to have both high sensitivity and selectivity for Ley among other carbohydrate antigens.

Anion inhibitors of the ß-carbonic anhydrase from the pathogenic bacterium responsible of tularemia, Francisella tularensis.

A ß-class carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium Francisella tularensis (FtußCA) was cloned and purified, and the anion inhibition profile was investigated. Based on the measured kinetic parameters for the enzyme catalyzed CO2 hydration reaction (kcat of 9.8×105s-1 and a kcat/KM of 8.9×107M-1s-1), FtußCA is a highly effective enzyme. The activity of FtußCA was not inhibited by a range of anions that do not typically coordinate Zn(II) effectively, including perchlorate, tetrafluoroborate, and hexafluorophosphate. Surprisingly, some anions which generally complex well with many cations, including Zn(II), also did not effectively inhibit FtußCA, e.g., fluoride, cyanide, azide, nitrite, bisulphite, sulfate, tellurate, perrhenate, perrhuthenate, and peroxydisulfate. However, the most effective inhibitors were in the range of 90-94µM (sulfamide, sulfamic acid, phenylarsonic and phenylboronic acid). N,N-Diethyldithiocarbamate (KI of 0.31mM) was a moderately potent inhibitor. As Francisella tularensis is the causative agent of tularemia, the discovery of compounds that can interfere with the life cycle of this pathogen may result in novel opportunities to fight antibiotic drug resistance.

A DFT Study of the Geometrical, Spectroscopical and Reactivity Properties of Diindolylmethane-Phenylboronic Acid Hybrids.

The structure of the ortho-, meta- and para- hybrid diindolylmethane-phenylboronic acids and their interactions were optimized with by a quantum chemical method, using density functional theory at the (DFT) level. Thus, infrared bands were assigned based on the scaled theoretical wavenumbers by correlating the respective experimental data of the molecules. In addition, the corresponding ¹H-/13C-/11B-NMR experimental and theoretical chemical shifts were correlated. The target molecules showed a poor treatment of the OH shifts in the GIAO method due to the absence of explicit solvent effects in these calculations; therefore, they were explicitly considered with acetone molecules. Moreover, the electron density at the hydrogen bond critical point increased, generating stabilization energy, from weak to moderate or weak to strong, serving as an indicator of the strength of the hydrogen bond between the different intermolecular interactions. Finally, some properties related to the reactive behavior of the target molecules associated with their cytotoxic effects and metabolic pathways were also calculated.