AUCTORES
Globalize your Research
Chat with us
Research Article | DOI: https://doi.org/10.31579/2690-1897/202
College of Chemistry and Material Science, Shandong Agricultural University, Taian City 271018, Shandong Prov., P.R. China.
*Corresponding Author: Nan Lu, Shandong Agricultural University, Taian City 271018, Shandong Prov., P.R. China.
Citation: Nan Lu, Chengxia Miao, (2024), Theoretical investigation on Brønsted acid-catalyzed cascade ring open-ing and double cyclization of 3-ethoxy cyclobutanone with naphthol to synthesize 2,8-dioxabicyclo [3.3.1] nonane, J, Surgical Case Reports and Images, 7(6); DOI:10.31579/2690-1897/202
Copyright: © 2024, Nan Lu. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 01 July 2024 | Accepted: 12 July 2024 | Published: 18 July 2024
Keywords: Naphthol; ring-opening; cyclobutanone; (3+3) annulation; bicyclic ketal
The mechanism is investigated for cascade ring-opening/cyclization of 3-ethoxy 2-phenyl cyclobutanone with 2-naphthol leading to 2,8-dioxabicyclo[3.3.1]nonane. After protonation of carbonyl group, the nucleophilic attack of 2-naphthol prompts ring-opening of cyclobutanone. The enolization and ethanol removal generate alkenone with recovered naphthalene hydroxyl, which follows two possible pathways. In path A, another 2-naphthol facilitates Michael addition to render enol intermediate, which then affords desired product via dioxygen double cyclization containing three steps. In path B, the protonation from hydroxyl helps cyclization furnishing dihydropyrylium. With another deprotonated 2-naphthol, (3+3) annulation directly forms product and is more favorable than path A. Under the impact of Brønsted acid, positive (3+3) annulation is further improved with low barrier. The positive solvation effect is suggested by decreased absolute and activation energies in solution compared with in gas. These results are supported by Multiwfn analysis on FMO composition of specific TSs, and MBO value of vital bonding, breaking.
The 2,8-dioxabicyclo[3.3.1]nonanes are privileged members in numerous heterocyclic frameworks embedded with two oxygen atoms [1,2]. Since these bicyclic moieties constitute flavonoid compounds, they exhibit powerful anti-inflammatory, antiviral, antioxidant, and anticancer activities as several important drugs [3,4]. Characterized by rigid V-shaped diaryl-substituted structure, the construction of these bicyclic cores has received wide interest in recent years [5]. In this aspect, most methods and protocols require similar precursor of 2-hydroxy chalcones with different partners such as sequential knoevenagel condensation and hetero-Diels-Alder reaction in aqueous medium, cerium(III)-catalyzed domino approach using polyphenols and 1,4-Zwitterionic intermediates generated by regioselective cleavage of cyclobutane ring followed by their cycloaddition [6-8]. Then Zhu reported cationic-lanthanide-complex-catalyzed reaction with naphthols [9]. Wang developed controllable synthesis of two isomers 4H chromene under catalyst-free conditions [10]. Li achieved switchable synthesis of cyclohexanedione-fused 2,8-oxaza/2,8-dioxa bicyclo[3.3.1]nonanes by tunability of deamination/dehydration process [11].
The 1,4-zwitterionic intermediate generated from cleavage of C2−C3 bond was common before various ring opening, cycloaddition or rearrangement catalyzed by Lewis acid. In past few decades, many examples appeared such as intermolecular [4 + 2] cycloaddition of 3-alkoxycyclobutanone to aldehyde and ketone, synthesis of pyrazole through union of monosubstituted hydrazine with 3-ethoxycyclobutanone, total synthesis of (±)-aspidospermidine and regioselective inter-and intramolecular formal [4 + 2] cycloaddition of cyclo-butanone with indole, [3 + 3] annulation to construct pyrimidine and pyridine, between aromatic amine and 3-ethoxycyclobutanone to 2-lkylquinoline, remote site-selective Friedel-Crafts alkylation of β-Naphthol [12-17]. Okado achieved (±)-bremazocine, 2,3-di- or 2,3,3-trisubstituted N-Ts-2,3-dihydro-4-pyridone by using reaction of N-p-Toluenesulfonyl (Ts) aldimine with 3-ethoxycyclobutanone prompted by titanium(IV) chloride [18]. Lin reported diversity-oriented synthesis of bioactive pyridine-containing fused heterocycle through union of 3-ethoxycyclobutanone with various heterocyclic amine with excellent regioselectivity [19]. In despite of these progresses, activation of four-membered ring via Brønsted acid (BA) is few. Only Xu obtained enantioselective Baeyer–Villiger oxidation of 3-substituted cyclobutanone giving γ-lactone [20].
However, it is still rare for direct ring-opening or cyclization with 3-ethoxy cyclobutanone catalyzed by BA. As far as we know, the development in recent years was Rahmatpour’s regioselective synthesis of di-aromatic ring-fused 2,8-dioxa/dithia bicyclo[3,3,1]nonane via recyclable tandem formation of multiple chemical C-C/C-O and C-C/C-S bonds [21]. In this context, a breakthrough was Hazra’s cascade ring-opening/cyclization of 3-ethoxy cyclobutanone [22]. Furthermore, this type of complex 15-membered macrocycle containing heteroatom was important biologically showing inhibitory and antitumor activities [23-25]. Although a range of 2,8-dioxabicyclo[3.3.1]nonane were obtained with various substituted naphthol, many problems still puzzled and there was no report about detailed mechanistic study explaining BA activation. What is the priority for carbonyl protonation of cyclobutanone and polarization of C2−C3 bond? How double cyclization is initiated from two oxygen atoms of two naphthols after Michael addition? Why (3+3) annulation with another 2-naphthol also possible from dihydropyrylium-type intermediate after cyclization from hydroxyl group? To solve these questions in experiment, an in-depth theoretical study was necessary for this strategy focusing on the competition of dioxygen-initiated double cyclization and (3+3) annulation.
Optimized structures were obtained at M06-2X/6-31G(d) level of theory with GAUSSIAN09 [26]. In tests of popular DFT methods [27], M06-2X functional attained smaller standard deviation of difference between calculated value and experimental value in geometries than B3LYP including Becke's three-parameter hybrid functional combined with Lee−Yang−Parr correction for correlation [28,29]. The best compromise between accuracy and time consumption was provided with 6-31G(d) basis set on energy calculations. Also, M06-2X functional was found to give relatively accurate results for catalysed enantioselective (4 + 3), concerted [4 + 2], stepwise (2 + 2) cycloaddition and catalysed Diels−Alder reactions [30,31]. Together with the best performance on noncovalent interaction, M06-2X functional is believed to be suitable for this system [32-34]. The nature of each structure was verified by performing harmonic vibrational frequency calculations. Intrinsic reaction coordinate (IRC) calculations were examined to confirm the right connections among key transition-states and corresponding reactants and products. Harmonic frequency calculations were carried out at the M06-2X/6-31G(d) level to gain zero-point vibrational energy (ZPVE) and thermodynamic corrections at 298.15 K and 1 atm for each structure in toluene.
The solvation-corrected free energies were obtained at the M06-2X/6-311++G(d,p) level by using integral equation formalism polarizable continuum model (IEFPCM) in Truhlar’s “density” solvation model [35-39] on the M06-2X/6-31G(d)-optimized geometries. As an efficient method obtaining bond and lone pair of a molecule from modern ab initio wave functions, NBO procedure was performed with Natural bond orbital (NBO3.1) to characterize electronic properties and bonding orbital interactions [40-42]. The wave function analysis was provided using Multiwfn_3.7_dev package [43] including research on frontier molecular orbital (FMO) and Mayer bond order (MBO).
The mechanism was explored for BA-catalyzed cascade ring-opening/cyclization of 3-ethoxy 2-phenyl cyclobutanone 1 with 2-naphthol 2 leading to 2,8-dioxabicyclo [3.3.1] nonane 3 (Scheme 1). Illustrated by black arrow of Scheme 2, initially the carbonyl group protonation of 1 polarize the C2−C5 bond. Then via the nucleophilic attack of 2 at C2 center, the ring-opening of 1 happen leading to intermediate I. Eventually the enolization and removal of ethanol generate intermediate II, which follows two possible pathways. In path A, another molecule 2 facilitates Michael addition to render intermediate III, which then affords desired product 3 via double cyclization from two oxygen atoms of two molecules of 2 (red arrow). In path B, the protonation of II carbonyl group by hydroxyl of 2 facilitates cyclization furnishing dihydropyrylium. Subsequently, a (3+3) annulation with another deprotonated 2 leads to product 3 (blue arrow). Under the impact of BA the positive (3+3) annulation takes place via three steps (green arrow). The schematic structures of optimized TSs in Scheme 2 were listed by Figure 1. The activation energy was shown in Table 1 for all steps. Supplementary Table S1, Table S2 provided the relative energies of all stationary points. According to experiment, the Gibbs free energies in methanol solution phase are discussed here.
Scheme 1 (a) Brønsted acid (BA)-catalyzed cascade ring-opening/cyclization of 3-ethoxy 2-phenyl cyclobutanone 1 with 2-naphthol 2 leading to 2,8-dioxabicyclo [3.3.1] nonane 3.
Scheme 2: Proposed reaction mechanism of BA-catalyzed cascade ring-opening/cyclization of 1 with 2 leading to 3. TS is named according to the two intermediates it connects.
Table 1: The activation energy (in kcal mol−1) of all reactions in gas and solvent
(b)
(c)
3.1 Protonation/ring-opening/enolization/ethanol removal and enol isomerization
Initially the complex of 1 and 2 denoted as i0, the carbonyl group of 1 is protonated by hydroxyl of 2 polarizing the C2−C5 bond. This process proceeds via ts-i01 as step 1 with the activation energy of 15.7 kcal mol−1 relative to the starting point i0 endothermic by 4.2 kcal mol−1 (black dash line of Figure 1a). The transition vector includes the transfer of H1 from O1 to O2 and the closing of O1 to C4 makes it changing from sp2 hybrid to sp3 (1.21, 1.25, 1.79 Å) (Figure S1a). Without proton, the reactive hydroxyl O1 is bonded to sp3 C4 in resultant i1, from which the ring-opening of 1 happen under the nucleophilic attack of 2 at C2 center leading to intermediate I. As step 2, this occurs via ts-i1I with activation energy of 26.8 kcal mol−1 exothermic by -14.9 kcal mol−1. The transition vector contains cleavage of C2···C5 and concerted linkage of C1···C2 (2.28, 2.51 Å). Therefore I is stable after releasing the tension of quadruple ring of 1. While once bonded to C2, the C1 turns to be sp3 hybrid breaking the conjugation of naphthalene ring apt to kick off a hydrogen in following process.
Then the enolization of carbonyl O1 takes place via ts-Ii2 in subsequent step 3 with activation energy of 25.5 kcal mol−1 affording i2 exothermic by -6.4 kcal mol−1. According to the transition vector, the proton H2 is transferring from C1 to O1, which is recovered to hydroxyl group O1H2. In next step 4, the OEt bonded to C2 and H on C3 are disconnected simultaneously and assemble stable EtOH molecule leaving from the system. Via ts-i23, ethanol is removed with a barrier of 16.3 kcal mol−1 exothermic by -15.5 kcal mol−1 delivering intermediate i3. The transition vector corresponds to the elongation of C2-O3, C3-H3 single bond to dissociation and bonding of O3-H3, C2-C3 shortened from single to double one at the same time (1.69, 1.59, 1.14, 1.45 Å) (Figure S1b).
Without ethanol, the intermediate II-0 is taken as new starting point of step 5 (red dash line of Figure 1a). The O2H1 hydroxyl group formed in step 1 denotes H1 to sp2 C5 to complete enol tautomerism. This happens via ts-II with activation energy of 21.7 kcal mol−1 exothermic by -11.2
kcal mol−1 yielding intermediate II more stable. The transition vector suggests remarkable O2···H1···C5 shifting as well as C4-C5 stretching from double bond to single.
3.2 Michael addition/dioxygen double cyclization
Two pathways are possible from II. In path A (black dash line of Figure 1b), the addition of another molecule 2 forms complex i4 as starting point of the following six steps. As preparation of Michael addition, the step 6 takes place via ts-i45 with activation energy of 15.5 kcal mol−1 forming reactive i5 endothermic by 5.4 kcal mol−1. Similar with ts-i01, the carbonyl O2 is protonated by new naphthyl hydroxyl O4H4. According to the transition vector, the atomic motion is composed of O4···H4···O2 proton shifting and laggered approaching of O4···C4 (1.58, 1.16, 2.37 Å). This greatly facilitate the crucial Michael addition seen from the low barrier via hexagonal ring structure of ts-i5III. Seen from the detailed motion demonstrated by its transition vector (Figure S1c), the departure of O4-C4 bond is accompanied by formation of C6-C2 bond (2.18, 2.35 Å). Clearly, the cleavage of O4-C4 endows negative charge concentrated on O4, passes on to C6 and enhance its nucleophilic ability. Likewise, the ability of C2 as an electrophilic center is also increased. Hence the small activation energy of step 7 is only 6.7 kcal mol−1 endothermic by 1.9 kcal mol−1 giving III-0, which is lower than former i5 in relative energy yet still reactive to initiate next step.
In step 8, III-0 undergoes carbonyl enolization of the second 2 via ts-III just like ts-Ii2 with activation energy of 23.4 kcal mol−1 exothermic by -2.5 kcal mol−1 generating III favorable in thermodynamics. The transition vector of this second enolization is about proton transfer of C6···H5···O4 (1.52, 1.26 Å), which not only recovers hydroxyl O4H5 but turns sp3 C6 in III-0 to be sp2 stable conjugated structure of naphthalene ring in III. From III, the desired product 3 is produced via double cyclization from two oxygen of two 2 molecule through three steps. The first nucleophilic attack of O4 to C4 proceeds via ts-IIIi6 followed by proton H5 given by O4 to C3 concertedly. This can be illustrated in detail by the transition vector (1.59, 1.17, 2.47 Å), which makes C3 methylene on the one hand and improves the nucleophilic ability of O4 on the other. The activation energy of step 9 is 9.2 kcal mol−1exothermic by -9.8 kcal mol−1 relative to III.
Before the second nucleophilic addition of O1 to C4, the dehydration is located via ts-i67 with activation energy of 27.3 kcal mol−1 exothermic by -6.8 kcal mol−1 as step 10. This is also belongs to small molecule H2O assembling and then leaving process similar to the case of EtOH removal via ts-i23. Here, the O2H4 on C4 combines with H2 on O1 as one water (1.77, 1.57, 1.18 Å) (Figure S1d) in resulting i7, which is stable although O1 and C4 is not yet connected owing to the distance. The real O1-C4 single bond should be achieved in last step 11 via ts-i78 with activation energy of 29.5 kcal mol−1 endothermic by 7.6 kcal mol−1 only involving simple O1···C4 approaching (1.88 Å). The barrier is somewhat high due to the need of overcoming tension generated by spatial distance.
Ultimately, the third simple step of dioxygen double cyclization is determined to be rate-limiting for path A. To highlight the idea of feasibility for changes in electron density and not molecular orbital interactions are responsible of the reactivity of organic molecules, quantum chemical tool Multiwfn was applied to analyze of electron density such as MBO results of bonding atoms and contribution of atomic orbital to HOMO of typical TSs (Table S3, Figure S2). These results all confirm the above analysis.
3.3 Cyclization from hydroxyl/(3+3) annulation and BA impact
In path B, the carbonyl O2 can also be protonated by original hydroxyl O1H2 from II via ts-IIin1 in step 6 with a barrier of 10.2 kcal mol−1 exothermic by -2.0 kcal mol−1delivering in1. The transition vector corresponds to simple proton H2 transfer from O1 to O2 (1.36, 1.12 Å) (Figure S1e). This faciliates first cyclization from O1 to C4 via ts-in12 as step 7 with the activation energy of 18.1 kcal mol−1 relative to in1 exothermic by -8.3 kcal mol−1 (black dash line of Figure 1c). Therefore the difficult nucleophilic addition of O1 to C4 in path A becomes readily accessible in path B, which is approved by the transition vector of ts-in12.
After the removal of O2H2 from cyclization product in2, a dihydropyrylium is obtained, which is easily binding the second deprotonated 2 via C6-C2 bond forming in3 as new starting point of subsequent step 3 (red dash line of Figure 1c). The second cyclization from O4 to C4 occurs via ts-in33 with activation energy of 23.3 kcal mol−1 by exothermic -24.7 kcal mol−1 directly leading to 3. The transition vector reveals a concerted asynchronous process containing previous C3 methylenation by C6 via C6···H5···C3 atomic motion and O4···C4 linking afterwords (1.52, 1.35, 2.53 Å) (Figure S1f). Evidently for path B, (3+3) annulation includes two steps with the second concerted one as rate-limiting more favorable than that of path A from kinetics.
The impact of BA are also considered for preferential (3+3) annulation modeled as a system with one positive charge (blue dash line of Figure 1c). The initial complex binding dihydropyrylium and neutral 2 denoted as in4+h is taken as starting point of the next two steps. The subsequent step 3 takes place via ts-in45+h with activation energy of 7.8 kcal mol−1 affording in5+h exothermic by -7.2 kcal mol−1, where C3 is methylenated by O4 via O4···H6···C3 and C6···C2 is bonding in concerted mode. Then via ts-in53+h with a rather low barrier of 3.3 kcal mol−1, O4-C4 single bond is accomplished in step 4 delivering 3+h exothermic by -20.7 kcal mol−1 as precusor of 3. Assisted by BA, the (3+3) annulation becomes easier involving three steps with the first O1···C4 bonding as rate-limiting comparatively.
Our DFT calculations provide the first theoretical investigation on cascade ring-opening/cyclization of 3-ethoxy 2-phenyl cyclobutanone with 2-naphthol leading to 2,8-dioxabicyclo[3.3.1]nonane. The carbonyl group of cyclobutanone is initially protonated by hydroxyl of 2-naphthol, the nucleophilic attack of which prompts ring-opening of cyclobutanone. The subsequent enolization and removal of ethanol generate alkenone intermediate with recovered naphthalene hydroxyl, which follows two possible pathways. In path A, another 2-naphthol facilitates Michael addition to render enol intermediate, which then affords desired product via dioxygen double cyclization containing three steps with the third simple O1···C4 approaching as rate-limiting. The barrier is somewhat high due to the tension generated by spatial distance yet readily to overcome under room temperature. In path B, the protonation from hydroxyl helps cyclization furnishing dihydropyrylium. With another deprotonated 2-naphthol, (3+3) annulation includes two steps with the second concerted O4···C4 bonding and C3 methylenation by C6 as rate-limiting, which directly forms product and is more favorable than path A from kinetics. Under the impact of BA the positive (3+3) annulation involves three steps with the first O1···C4 bonding as rate-limiting comparatively. The positive solvation effect is suggested by decreased absolute and activation energies in toluene solution compared with in gas. These results are supported by Multiwfn analysis on FMO composition of specific TSs, and MBO value of vital bonding, breaking.
Supplementary data available: [Computation information and cartesian coordinates of stationary points; Calculated relative energies for the ZPE-corrected Gibbs free energies (ΔGgas), and Gibbs free energies (ΔGsol) for all species in solution phase at 298 K.]
Conceptualization, Nan Lu; Methodology, Nan Lu; Software, Nan Lu; Validation, Nan Lu; Formal Analysis, Nan Lu; Investigation, Nan Lu; Resources, Nan Lu; Data Curation, Nan Lu; Writing-Original Draft Preparation, Nan Lu; Writing-Review & Editing, Nan Lu; Visualization, Nan Lu; Supervision, Chengxia Miao; Project Administration, Chengxia Miao; Funding Acquisition, Chengxia Miao. All authors have read and agreed to the published version of the manuscript.
This work was supported by National Natural Science Foundation of China (21972079) and Key Laboratory of Agricultural Film Application of Ministry of Agriculture and Rural Affairs, P.R. China.
The authors declare no conflict of interest.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
