Intermolecular Hydrogen-bonding Interactions Research Articles

Supramolecular self-assembly of micro spherical CL-20/TNT energetic Co-crystal

We reported an ultrasonic-assisted emulsion approach for the synthesis of micro spherical CL-20/TNT energetic co-crystal via supramolecular self-assembly. It was demonstrated that the architected CL-20/TNT co-crystal displays advanced thermal properties and improved sensitivity performance. For the micro spherical CL-20/TNT co-crystal with mean practical size = 6.8 μm, it has only one decomposing peak at 254.8 °C and higher impact sensitivity (H50: 57.8 cm) and lower friction (41%). Herein, for the first time, organic energetic co-crystal of micro spheres was synthesized by simultaneously tailoring the energy level and safety based on the intermolecular hydrogen-bonding interactions. This novel strategy is expected to provide new opportunities for exploring the synthesis of various organic micro spherical co-crystals towards their applications.

Structural Studies of Monounsaturated and ω-3 Polyunsaturated Free Fatty Acids in Solution with the Combined Use οf NMR and DFT Calculations-Comparison with the Liquid State.

Molecular structures, in chloroform and DMSO solution, of the free fatty acids (FFAs) caproleic acid, oleic acid, α-linolenic acid, eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) are reported with the combined use of NMR and DFT calculations. Variable temperature and concentration chemical shifts of the COOH protons, transient 1D NOE experiments and DFT calculations demonstrate the major contribution of low molecular weight aggregates of dimerized fatty acids through intermolecular hydrogen bond interactions of the carboxylic groups, with parallel and antiparallel interdigitated structures even at the low concentration of 20 mM in CDCl3. For the dimeric DHA, a structural model of an intermolecular hydrogen bond through carboxylic groups and an intermolecular hydrogen bond between the carboxylic group of one molecule and the ω-3 double bond of a second molecule is shown to play a role. In DMSO-d6 solution, NMR and DFT studies show that the carboxylic groups form strong intermolecular hydrogen bond interactions with a single discrete solvation molecule of DMSO. These solvation species form parallel and antiparallel interdigitated structures of low molecular weight, as in chloroform solution. This structural motif, therefore, is an intrinsic property of the FFAs, which is not strongly affected by the length and degree of unsaturation of the chain and the hydrogen bond ability of the solvent.

Computational-based drug design of novel small molecules targeting p53-MDMX interaction

The regulation of the p53 tumor suppressor pathway is critically dependent on the activity of Murine Double Minute 2 (MDM2) and Murine Double Minute X (MDMX) proteins. In certain types of cancer cells, excessive amount of MDMX can poly-ubiquitinate p53, which can result in its degradation, leading to a subsequent reduction in the levels of this protein. Therefore, the design of small-molecule inhibitors targeting the MDMX-p53 interaction has emerged as a promising strategy for cancer therapy. In this study, we employed computational techniques including pharmacophore modeling and molecular docking to identify three potential small molecule inhibitors (CID_25094615, CID_137634453, and CID_25094344) of the MDMX-p53 interaction from a PubChem database. Molecular dynamics of 100000 ps were conducted to assess the stability of the MDMX-inhibitor complexes. Our results showed that all three compounds exhibit stable binding with MDMX, with significantly lower root mean square deviation (RMSD) and fluctuation (RMSF) values than the control ligand, indicating superior stability. Additionally, the three compounds exhibit stronger intermolecular hydrogen bond (HBOND) interactions compared to the control, suggesting stronger stability. Overall, our findings highlight the potential of these compounds as lead candidates for the development of novel anticancer agents that target the MDMX-p53 interaction. Communicated by Ramaswamy H. Sarma

Nano Proteolysis Targeting Chimeras (PROTACs) with Anti-Hook Effect for Tumor Therapy.

Proteolysis targeting chimera (PROTAC) is an emerging pharmacological modality with innovated post-translational protein degradation capabilities. However, off-target induced unintended tissue effects and intrinsic "hook effect" hinder PROTAC biotechnology to be maturely developed. Herein, an intracellular fabricated nano proteolysis targeting chimeras (Nano-PROTACs) modality with a center-spoke degradation network for achieving efficient dose-dependent protein degradation in tumor is reported. The PROTAC precursors are triggered by higher GSH concentrations inside tumor cells, which subsequently in situ self-assemble into Nano-PROTACs through intermolecular hydrogen bond interactions. The fibrous Nano-PROTACs can form effective polynary complexes and E3 ligases degradation network with multi-binding sites, achieving dose-dependent protein degradation with "anti-hook effect". The generality and efficacy of Nano-PROTACs are validated by degrading variable protein of interest (POI) such as epidermal growth factor receptor (EGFR) and androgen receptor (AR) in a wide-range dose-dependent manner with a 95 % degradation rate and long-lasting potency up to 72 h in vitro. Significantly, Nano-PROTACs achieve in vivo dose-dependent protein degradation up to 79 % and tumor growth inhibition in A549 and LNCap xenograft mice models, respectively. Taking advantages of in situ self-assembly strategy, the Nano-PROTACs provide a generalizable platform to promote precise clinical translational application of PROTAC.

A novel ratiometric fluorescent probe based on dual-emission carbon dots for highly sensitive detection of salicylic acid

In this study, a novel ratiometric fluorescence probe based on dual-emission carbon dots (CDs) for the sensitive detection of salicylic acid (SA) was constructed for the first time. The dual-emission CDs were synthesized by simple hydrothermal method using tartaric acid (TA) and m-phenylenediamine (mPD) as raw materials. In the presence of SA, the fluorescence intensity of CDs was enhanced at 499 nm, but remained basically unchanged at 439 nm. This phenomenon is caused by the intermolecular hydrogen bond interactions. The concentrations of SA had an excellent linear relationship with CDs' fluorescence intensity ratio (F499/F439) in a range of 1 ∼ 120 and 120 ∼ 240 μM with low detection limits of 0.68 and 1.05 μM. The established ratiometric fluorescent probe is economical, simple and green, and can be used for the effective detection of SA. In addition, the proposed ratiometric fluorescent probe was successfully used to monitor SA in facial mask and toning lotion samples with a satisfactory recovery of 99.7–106.7 %. The results show that the constructed fluorescent probe based on dual-emission CDs has a great potential for the rapid and sensitive analysis of SA in actual samples.

Nano Proteolysis Targeting Chimeras (PROTACs) with Anti‐Hook Effect for Tumor Therapy

AbstractProteolysis targeting chimera (PROTAC) is an emerging pharmacological modality with innovated post‐translational protein degradation capabilities. However, off‐target induced unintended tissue effects and intrinsic “hook effect” hinder PROTAC biotechnology to be maturely developed. Herein, an intracellular fabricated nano proteolysis targeting chimeras (Nano‐PROTACs) modality with a center‐spoke degradation network for achieving efficient dose‐dependent protein degradation in tumor is reported. The PROTAC precursors are triggered by higher GSH concentrations inside tumor cells, which subsequently in situ self‐assemble into Nano‐PROTACs through intermolecular hydrogen bond interactions. The fibrous Nano‐PROTACs can form effective polynary complexes and E3 ligases degradation network with multi‐binding sites, achieving dose‐dependent protein degradation with “anti‐hook effect”. The generality and efficacy of Nano‐PROTACs are validated by degrading variable protein of interest (POI) such as epidermal growth factor receptor (EGFR) and androgen receptor (AR) in a wide‐range dose‐dependent manner with a 95 % degradation rate and long‐lasting potency up to 72 h in vitro. Significantly, Nano‐PROTACs achieve in vivo dose‐dependent protein degradation up to 79 % and tumor growth inhibition in A549 and LNCap xenograft mice models, respectively. Taking advantages of in situ self‐assembly strategy, the Nano‐PROTACs provide a generalizable platform to promote precise clinical translational application of PROTAC.

Investigation of luminescent and liquid crystalline properties of the supramolecular hydrogen bonded complexes formed from non-mesogenic pyridine derivatives and lauric acid

Hydrogen bonds are the best non-covalent interactions for building supramolecular structures. Nowadays, hydrogen bonded supramolecular liquid crystals are quickly evolving into a versatile, simple, and affordable method for new smart materials. Therefore, through intermolecular hydrogen bond interactions, a homologous series of supramolecular mesogenic systems are prepared in the present study. The non-mesogenic hydrogen bond acceptors i.e. 2-(4-alkoxyphenyl)-5-(pyridin-4-yl)-1,3,4-oxadiazoles (OXn) are synthesized, the structures are confirmed using various techniques (1H NMR, 13C NMR, ESI-MS, and elemental analysis) and their photophysical properties are studied in the solid state as well as in solution state. Moreover, the DFT study indicated the planar structure with greater intramolecular charge transfer between donors and acceptors. In addition, these molecules (OXn) are made to form a hydrogen bond with the non-mesogenic fatty acid i.e. Lauric acid (LA). The formation of the hydrogen bonds in the prepared supramolecular complex (OXn/LA) is confirmed by using the ATR-IR analysis. Further, red shifted solid state emission spectra are noted for the complexes (OXn/LA) compared to the parent molecules (OXn). The mesogenic properties of the prepared OXn/LA complexes are studied via differential scanning calorimetry, polarized optical microscopy, and X-ray diffractometry. It was found that the complexes OX-8/LA and OX-10/LA exhibit monotropic SmA mesophase, however, the remaining complexes are non-mesogenic in nature.

A sulfonylcalix[4]arene-based metal–organic cage with octahedral porous structure for guest adsorption and separation

A novel sulfonylcalix[4]arene-based metal-organic cage (MOC), [{Co4(µ4-H2O)(TBSC)}6L12] (Co-1), was synthesized by self-assembly of the ligand 2,3-dihydroxyterephthalic acid (H2L), p-tert-butylsulfonylcalix[4]arene (H4TBSC), and Co(NO3)2 using a solvothermal method. Based on single-crystal X-ray analysis, the molecular structure of Co-1 features a truncated octahedron cage with one inner and six outer cavities. Discrete MOCs are further stacked into a 3D porous supramolecular structure through abundant intermolecular hydrogen-bonding interactions. Additionally, the guest adsorption and separation properties of Co-1 were investigated by using UV-vis spectrophotometer. The results demonstrated that Co-1 exhibits high adsorption capacity of methylene blue and excellent dye selective separation performance.

Bioinspired, Anticoagulative, 19 F MRI-Visualizable Bilayer Hydrogel Tubes as High Patency Small-Diameter Vascular Grafts.

The clinical patency of small-diameter vascular grafts (SDVGs) (ID < 6mm) is limited, with the formation of mural thrombi being a major threat of this limitation. Herein, a bilayered hydrogel tube based on the essential structure of native blood vessels isdeveloped by optimizing the relation between vascular functions and the molecular structure of hydrogels. The inner layer of the SDVGs comprises a zwitterionic fluorinated hydrogel, avoiding the formation of thromboinflammation-induced mural thrombi. Furthermore, the position and morphology of the SDVGs canbe visualized via 19 F/1 H magnetic resonance imaging. The outer poly(N-acryloyl glycinamide) hydrogel layer of SDVGs provides matched mechanical properties with native blood vessels through the multiple and controllable intermolecular hydrogen-bond interactions, which canwithstand the accelerated fatigue test under pulsatile radial pressure for 380 million cycles (equal to a service life of 10 years in vivo). Consequently, the SDVGs exhibit higher patency (100%) and more stable morphology following porcine carotid artery transplantation for 9 months and rabbit carotid artery transplantation for 3 months. Therefore, such a bioinspired, antithrombotic, and visualizable SDVG presents a promising design approach for long-term patency products and great potential of helping patients with cardiovascular diseases.

Intermolecular hydrogen-bonding as a robust tool toward significantly improving the photothermal conversion efficiency of a NIR-II squaraine dye

The photothermal therapy (PTT) has come across as a promising noninvasive therapeutic strategy for tumor treatment. However, low photothermal conversion efficiency (PCE) and hydrophobicity may impede the therapeutic efficacy of organic photothermal agents and an efficient PTT-agent must overcome these two major challenges. In this work, we developed a new strategy to promote higher PCE wherein the intermolecular hydrogen-bonding interaction between the single dye molecule and water facilitated the transformation of the absorbed energy into the heat. A hydrophilic squaraine dye (SCy1) with the second near-infrared region (NIR-II) absorption and extremely low emission were designed to exhibit much higher PCE than that of the analogues of pentamethine-dyes (PCy1, PCy2). The presence of the ‘–O−’ at middle of squaric cycle enabled the intermolecular H-bonding formation between the SCy1 and water to promote the energy dissipation channel. Moreover, the introduction of long-chain phenylsulfonate groups helped in to improve the water solubility apart from serving as an additional means of further enhancing PCE through fluorescence quenching. Therefore, SCy1 with a squaraine backbone and long-chain sulfonate moieties revealed outstanding photothermal stability and anti-aggregation activity apart from showing exceptionally high PCE (74%) in water. SCy1 demonstrated excellent therapeutic efficacy when applied in the PTT treatment of tumor-bearing mice under a laser irradiation of 915 nm.

An antibacterial Co(II) mononuclear compound containing N,N-bis(3,5-dichlorosalicylidene)hydrazine obtained from 3,5-dichlorosalicylaldehyde thiosemicarbazone in hydrothermal conditions

A mononuclear compound, [Co(L1)2(H2O)]·2H2O (1), where L1 = N,N-bis(3,5-dichlorosalicylidene)hydrazine, was synthesized under hydrothermal conditions. Note that L1 is derived from the hydrothermal in situ reaction of L2 (L2 = 3,5-dichlorosalicylaldehyde thiosemicarbazone). L2 is prepared by reflux using 3,5-dichlorosalicylic aldehyde and thiosemicarbazide. Although 1 is only a mononuclear structure coordinated with L1, intermolecular hydrogen-bonded interactions between two adjacent mononuclear units creates a 1D supramolecular chain. Furthermore, it self-assembles into a fascinating 2D supramolecular layer via π⋅⋅⋅π stacking between benzene rings of adjacent chains. Hirshfeld surfaces and fingerprint maps of 1 were applied to obtain data on non-covalent interactions. Antibacterial analysis shows that 1 is a potential antibacterial material and the bacteriostasis rate is higher than that of L1 (E. coli: 89.41% for 1, 29.09% for L1; MRSA: 93.17% for 1, 38.54% for L1). The solid and liquid photoluminescence properties of 1 and L1 were also investigated.

Investigation of the crystal structure, supramolecular architecture and in-silico myelofibrosis inhibition of a triazole derivative: a structural and theoretical approach

One of the most significant issues in contemporary medicine and pharmacy is the search for efficient, low-toxic anticancer medicines. In this contrast, present work involves the synthesis of 6-(4-bromophenyl)-3-(pyridin-4-yl)-7H-[1,2,4]triazolo[3,4-b[1,3,4]thiadiazine compound and its characterization using various spectroscopic techniques. Structural and Hirshfeld surface analysis inferred that the crystal packing is stabilized by several intra and intermolecular interactions, their nature and strength are corroborated by the quantum theory of atoms in molecules analysis. The H···H and C-H···N strong intra and intermolecular hydrogen bond interactions resulted in the formation of S(5), S(6) self-motifs and R22(10), R66(42) supramolecular ring motifs. Further, the electronic properties of the molecule were obtained using the density functional theory. The charge distribution on the molecular surface are analyzed using the molecular electrostatic potential map and Fukui analysis. The intramolecular hyper conjugations, and charge delocalization in the compound are analyzed by natural bond orbital analysis. The docking studies revealed that the molecule might possess potential anticancer activity against Janus tyrosine kinase 2 protein compared to pacritinib, and in silico ADMET pharmacokinetic properties indicate adherence to Lipinski's rule of five for favorable safety profiles.

Dynamics simulation of excited-state proton transfer reactions of 8-hydroxyquinoline with water clusters: A TD-DFT study

Detailed pictures of the excited-state proton transfer reactions of 8-hydroxyquinoline (8HQ) and its small clusters of water have been systematically investigated using density functional theory (DFT) and time-dependent DFT (TD-DFT) methods at B3LYP/TZVP and TD-B3LYP/TZVP level of theory, respectively. Intramolecular hydrogen bond (intraHB) and intermolecular hydrogen bond (interHB) interactions between 8HQ and water cluster become stronger in the first excited state (S1), confirmed by hydrogen bond distances and topological analysis. In addition, TD-B3LYP dynamics simulations have been elucidated and revealed that excited-state intramolecular proton transfer (ESIntraPT) and multiply excited-state intermolecular proton transfer (ESInterPT) reactions of these complexes can take place in the ultrafast time scale of femtoseconds. Increasing the number of water molecules may give rise to a barrier energy that is anti-correlated to the probability of tautomer species from phototautomerization, especially in 8HQ-W1 and 8HQ-W1+1. Moreover, water molecules initiate multiple proton transfer occurring through two- and three-step ESInterPT namely excited-state double proton transfer (ESDPT) and excited-state triple proton transfer (ESTPT) in which the interHBs are formed by rearrangement of water molecules of 8HQ-W2. This circumstance takes a longer time (up to 470 fs) compared to that of ESIntraPT. Thus, the simulated results from this study could provide insight into ESIntraPT and ESInterPT of phototautomerization and the significant photodynamics which could not be found from the experimental aspects of 8HQ and its solvent clusters.

Evaluation of physicochemical properties and in vitro starch digestion of noodles enriched with thermally assisted potassium carbonate treated sweet potato residue

In this study, we investigated the effect of thermally assisted potassium carbonate treatment sweet potato residue (TAPC-SPR) and its addition (0%, 5%, 10% and 15%) on the texture, multi-scale structure (microstructure, crystalline structure, short-range ordered structure) and in vitro starch digestibility of the noodles. The results demonstrated that the ratio of total dietary fiber (TDF) (75.62%–87.25%) and pectin (19.36%–23.36%) were increased, and the particle size distribution (175.67 μm–47.42 μm) was decreased in TAPC-SPR than sweet potato residues (SPR). This study suggested that suitable TAPC-SPR (5% and 10%) contributed to improving the texture properties of noodles, containing hardness, springiness, chewiness and adhesiveness. Sensory evaluation showed that noodles with suitable TAPC-SPR (5% and 10%) had an overall sensory acceptability relative to control. In addition, the intermolecular hydrogen bond interaction, the structure order, V-type starch complex and dense structure were observed. These structural changes limit the interaction of amylase with starch, elevate the resistant starch (RS) content, and lower the predicted glycemic index (pGI).

Fabrication of soy protein isolate - High methoxyl pectin composite emulsions for improving the stability and bioavailability of carotenoids

A handy and efficient emulsifying emulsion was developed based on self-assembled soy protein isolate (SPI) and high methoxy pectin (HMP) for entrapping and loading carotenoids. The complex, ca. 195 nm, showed a significant improvement in solubility, emulsification (32.42 m2/g) and stability (83.86%). Moreover, the physical stability of torularhodin was remarkably improved after entrapping into the SPI-HMP complex. The retention rate for entrapped torularhodin could be up to 66.03%, 95.14% and 84.31% under treatment with ultraviolet irradiation for 8 h, thermal stock at 25 and 50 °C for 28 days, respectively. Increase of two affinities, enhancement of intermolecular hydrogen bond and hydrophobic interaction and charge changes caused by the preparation process of the complex were the main reasons for improving the properties of emulsion. At the same time, composite lotion encapsulation significantly improves the bioavailability of torularhodin, including the absorption of carotenoids in the small intestine, the content in the systemic circulation and the storage capacity in the liver. Therefore, the preparation of low price, safer, green and efficient SPI-HMP complex emulsion has long-term application prospects on the development, transportation and application of antioxidants.

Study on the Preparation of Montmorillonite-Type Multiple Network Composite Gel for Coal Spontaneous Combustion and Its Firefighting Mechanism.

This paper proposes a new montmorillonite-type multiple network composite gel for the prevention of coal spontaneous combustion. The first network is formed by the cross-linking of polyvinyl alcohol (PVA) and boric acid under alkaline conditions. The second network is formed as a result of intermolecular hydrogen-bonding interactions between polyacrylamide (PAM) and polyvinyl alcohol. Montmorillonite (MMT) is designed as the backbone material in the preparation of composite gels. The optimal ratios of the reactants of the composite gel were determined through orthogonal experiments. The experimental results showed that PVA had the greatest influence on the gelation time, whereas the PAM concentration had the strongest influence on the gel permeability. The optimal blending ratio was 4% MMT + 2.5% PVA + 1.5% PAM. The chemical performances of the composite colloids, such as inhibition rate, reactive functional groups, and kinetics, were investigated. Results showed that multiple network composite gels could effectively inhibit the coal spontaneous combustion reaction. Based on the principle of coal spontaneous combustion and the cross-linking network structure of the composite gel, the flame-retardant and fire-extinguishing mechanisms were also explored in terms of both physical and chemical inhibition pathways.

Crystal structure studies, Hirshfeld surface analysis, 3D energy frameworks, computational studies and docking analysis of a 2-(4-nitrophenyl)-2-oxoethyl 2-methoxybenzoate

The compound 2-(4-nitrophenyl)-2-oxoethyl 2-methoxybenzoate, was synthesized and characterized using conventional analytical techniques. The compound which has molecular formula C16H13NO6 crystallizes in the monoclinic crystal system with the space group P21/n. The crystal structure is stabilized by CH…O intermolecular interactions. Hirshfeld surface analysis confirms the presence of CH…O intermolecular hydrogen bond interactions. Molecular orbital analysis was studied to know the chemical reactivity of the molecule using DFT calculations. MEP analysis shows the chemical reactive sites around oxygen and hydrogen atoms. Molecular docking studies were carried out for the compound with the 1KZN protein, which demonstrated that the molecule has a good binding affinity with the protein target. The results obtained are very encouraging.

Theoretical exploration on the molecular configurations, solubilities and chemical reactivities of four flavonoid-based co-crystals

Four flavonoid-based co-crystals containing the active pharmaceutical ingredients Apigenin (AP), 4′,7-Dihydroxyflavone (DH), Genistein (GE), Daidzein (DA) and the co-crystal former Theophylline (TH) were constructed as the stoichiometric ratio of 1:2 form in theory. The structural parameters and chemical reactivities of the four co-crystals were systematically explored via the density functional theory (DFT) and quantum theory of atoms in molecules (QTAIM) methods. The intermolecular hydrogen bond lengths, frontier molecular orbitals, absorption spectra, electrostatic potential population, binding energies, solvent energies and global reactivity descriptors of the monomers and co-crystal systems were studied. In addition, the topological analysis of bond critical point based on the QTAIM, interaction region indicator and infrared (IR) spectrum analysis were adopted to investigate the intermolecular interaction between the APIs and CCF. The calculated results indicate that the APIs and CCF are bound via the intermolecular hydrogen bond interaction, and the drug activity and solubility of all co-crystals are significantly improved compared with that of the monomers. Interestingly, the isoflavone-based co-crystals (DA-TH and GE-TH) show the more excellent drug activities than that of the flavonoid-based co-crystals (AP-TH and DH-TH). This work can provide the reliable theoretical basis for the experimental synthesis of flavonoid-based drug co-crystal with more outstanding properties.

NMR and DFT studies of monounsaturated and ω-3 polyunsaturated free fatty acids in the liquid state reveal a novel atomistic structural model of DHA

Structures of low-energy conformers of caproleic acid (CA; 10:1 cis-9), oleic acid (OA; 18:1 cis-9), α-linolenic acid (ALA; 18:3 cis-9,12,15 ω-3), eicosapentaenoic acid (EPA; 20:5 cis-5,8,11,14,17 ω-3), and docosahexaenoic acid (DHA; 22:6 cis-4,7,10,13,16,19 ω-3) in the liquid state, based on detailed 1D NOE and density functional theory calculations of 1H NMR chemical shifts are presented. Transient 1D NOE experiments with variable mixing time showed significant through-space proximity of the CH2–COOH protons and the terminal CH3– groups. Variable temperature 1H NMR experiments revealed strong intermolecular centro-symmetric cyclic hydrogen bond interactions of the carboxylic groups of the monounsaturated oleic and caproleic acids (δ(COOH) ∼ 12.0–12.4 ppm), ALA and EPA (δ(COOH) ∼ 11.0 ppm). On the contrary, the carboxylic proton of DHA is strongly shielded with δ(COOH) ∼ 8.5 ppm. DFT calculations were interpreted in terms of aggregates of dimerized fatty acids with parallel and antiparallel interdigitated structures. The antiparallel arrangement was found to be in excellent agreement with experimental 1D NOE NMR data. For the dimeric DHA, a flip-flop process between a classical intermolecular centro-symmetric hydrogen bond through carboxylic groups and a novel intramolecular hydrogen bond between the carboxylic group and the terminal ω-3 double bond is demonstrated.

Nanofibrous hybrid scaffolds based on PCL-borosilicate system by a green sol-gel process

Tissue regeneration is yet a critical issue, and to mimic the natural extracellular matrix (ECM) innovative scaffolds need to be developed to ensure the functional and safe repair of the damaged organs or tissues. Hybrid biomaterials based on the combination of a biodegradable polymer and bioactive glasses (BGs) are potential candidates for tissue engineering (TE), since they exhibit tailored physical, biological, and mechanical properties, as well as controlled degradation behavior. Thus, the main purpose of this research was to develop by electrospinning (ES) a hybrid nanofibrous membrane composed of a synthetic polymeric matrix (PCL) and a boron and calcium silicate glass, formed via in situ sol-gel, and based on a non-aqueous and green fabrication route. Formic acid (FA) and glacial acetic acid (AA) were used as green solvents to dissolve the PCL. Different compositions were prepared: neat PCL and PCL/SiO2–B2O3–CaO with different sol-gel aging times and green solvent systems. All prepared hybrid solutions, except the composition with only AA, were spinnable. Structural features of the hybrids were assessed by ATR-FTIR spectroscopy, which confirmed the presence of siloxane (Si–O–Si) bonds of silica and carbonyl (CO) bonds characteristic of PCL polymer as well as intermolecular hydrogen-bonding interactions between the carbonyls of PCL and the silanol hydroxyls (Si–OH) of silica networks. Boron (B–O–B) and borosiloxane (B–O–Si) bonds were not visible due to the overlapping of PCL bands in the spectra. Only the solid state 11B NMR technique allowed to find peaks assigned to trigonal BO3 and tetrahedral BO4 groups, which evidence the boron linkages to silica. Thermal analysis showed a change in the crystallinity of PCL with the incorporation of inorganic domains, confirming the formation of chemical interactions between the polymer and the inorganic part. Microstructure and chemical analysis, by SEM/EDS, showed a homogenous distribution of Ca and Si elements into the fibers, as well as an increase of the fiber diameter with the incorporation of boron and calcium silicate glass in the PCL. The developed compositions of PCL/boron and calcium-containing silicate were feasible to electrospin into fibrous meshes, proving its potential for further design of multicomponent nanofibrous microstructures closer to extra cellular matrix architectures.