Development of robust chiroptical systems through spirobifluorenes.

Chiroptical responses are valuable for the structural determination of dissymmetric molecules. However, the development of everyday applications based on chiroptical systems is yet to come. We have been earlier using axially chiral allenes for the construction of linear, cyclic, and cage-shaped molecules that present remarkable chiroptical responses. Additionally, we have developed chiral surfaces through upstanding chiral architectures. Since the goal is to obtain robust chiroptical materials, more recently we have been studying spirobifluorenes (SBFs), a well-established building block in optoelectronic applications. After theoretical and experimental demonstration, the suitability of chiral SBFs for the development of robust chiroptical systems was certified by the construction all-carbon double helices, flexible shape-persistent macrocycles, chiral frameworks for surface functionalization, and structures featuring helical or spiroconjugated molecular orbitals. Here, we give an overview of our contribution to these matters.

Distinct Helical Molecular Orbitals through Conformational Lock*.

Several theoretical studies have proposed strategies to generate helical molecular orbitals (Hel-MOs) in [n]cumulenes and oligoynes. While chiral even-[n] cumulenes feature Hel-MOs, odd-[n] cumulenes may also present them if the terminal groups lie in different planes. However, the proposed systems have been either experimentally unfeasible or resulted in opposite pseudo-degenerated Hel-MOs. We hereby demonstrate the introduction of a remarkable energy difference between helical orbitals of opposite twist by fixing the torsion angle between the terminal groups in butadiyne fragments. To experimentally lock the conformation of the terminal groups, we designed and synthesized cyclic architectures by combining acetylenes with chiral spirobifluorenes. The high stability of these systems with distinct helical orbitals allowed their isolation and full characterization. In our view, these results constitute a step further in the development of real systems presenting helical molecular orbitals.

Design and synthesis of chiral spirobifluorenes.

Chiroptical spectroscopic methods serve as a practical tool for the structural characterization of chiral systems based on the interaction with polarized light. The higher sensitivity of these methods, compared with their achiral counterparts, not only enables the determination of absolute configuration and conformational preferences, but also supramolecular interactions may be monitored. In order to expand the applicability of chiroptical systems, the development of functional materials exhibiting intense chiroptical responses is essential. As a proof of principle, we previously constructed chiroptical interfaces via thioacetate-derivatized allenes. Because of the photoisomerization issues associated with allenes, we have recently proposed their replacement by spirobifluorenes to achieve robust chiroptical systems. Thus, we hereby present the design and synthesis of chiral spirobifluorenes bearing thioacetates suitable for suface functionalization.

Chiroptical Sensing: A Conceptual Introduction.

Chiroptical responses have been an essential tool over the last decades for chemical structural elucidation due to their exceptional sensitivity to geometry and intermolecular interactions. In recent times, there has been an increasing interest in the search for more efficient sensing by the rational design of tailored chiroptical systems. In this review article, advances made in chiroptical systems towards their implementation in sensing applications are summarized. Strategies to generate chiroptical responses are illustrated. Theoretical approaches to assist in the design of these systems are discussed. The development of efficient chiroptical reporters in different states of matter, essential for the implementation in sensing devises, is reviewed. In the last part, remarkable examples of chiroptical sensing applications are highlighted.

RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients. METHODS: We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units. RESULTS: A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation. CONCLUSIONS: By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.

Spirobifluorene Metallaaromatics.

Spirobifluorene derivatives find use in many end-user applications. Therefore, further expansion of their scope is the focus of many research studies. However, although the optical properties of spirobifluorenes can be greatly tuned through incorporation of metal complexes, to date, spirobifluorene metallaaromatics remain unknown. Taking advantage of the versatility of our methodology for the synthesis of metallaaromatic systems, this work reports the first metallaaromatic spirobifluorene compound. The presence of an Ir atom was found to redshift the absorption maximum by ca. 1.1 eV compared to bare spirobifluorene. Additionally, X-ray analysis as well as anisotropy of the current-induced density calculations revealed this compound to be of aromatic nature. The high stability in solution, solid state, under air, and at high temperature, as well as distinct optical properties of this new class of compounds are expected to open new frontiers for chiroptical and optoelectronic applications.

Device-Compatible Chiroptical Surfaces through Self-Assembly of Enantiopure Allenes.

Chiroptical methods have been proven to be superior compared to their achiral counterparts for the structural elucidation of many compounds. To expand the use of chiroptical systems to everyday applications, the development of functional materials exhibiting intense chiroptical responses is essential. Particularly, tailored and robust interfaces compatible with standard device operation conditions are required. Herein, we present the design and synthesis of chiral allenes and their use for the functionalization of gold surfaces. The self-assembly results in a monolayer-thin room-temperature-stable upstanding chiral architecture as ascertained by ellipsometry, X-ray photoelectron spectroscopy, and near-edge X-ray absorption fine structure. Moreover, these nanostructures anchored to device-compatible substrates feature intense chiroptical second harmonic generation. Both straightforward preparation of the device-compatible interfaces along with their chiroptical nature provide major prospects for everyday applications.

Diverse Chiral Scaffolds from Diethynylspiranes: All-Carbon Double Helices and Flexible Shape-Persistent Macrocycles.

State-of-the-art chiroptical spectroscopies are valuable tools for structural elucidation. However, the potential of these spectroscopies for everyday applications has not been exploited to date partially due to the lack of sufficiently stable and efficient chiroptical systems. To this end, the development of suitable chiroptical structures is essential. Herein, we present the synthesis of spiro-compounds (P2 )-1 and (P4 )-2 as well as (M2 )-1 and (M4 )-2 exhibiting remarkable chiroptical responses. Theoretical simulations show that (P2 )-1, constituted by two (P)-configured spiranic chiral axes, presents an all-carbon double helix structure with (M)-helicity. On the other hand, molecular dynamic simulations reveal (P4 )-2 to have a single path for geometry-modification along its flat conformational space, certifying it as a chiral flexible shape-persistent macrocycle. Geometric quantification of chirality has been used to compare the spiranic derivatives presented herein.

A Covalent Organic Helical Cage with Remarkable Chiroptical Amplification.

Purely organic shape-persistent chiral cages are designed through the use of rigid chiral axes. Covalent dimerization of a tripodal fragment bearing chiral allenes forms a molecular twisted prism with loop-like lateral edges presenting 10-fold chiroptical amplification compared to its isolated building blocks. The expected geometry of covalent organic helical cage (M,M)3 -1 was confirmed by X-ray crystal structure analysis. Comparison of the chiroptical responses of this shape-persistent molecular container with more flexible analogues highlights how the control of the conformational freedom of the molecule can be used to obtain molecular cages with strong chiroptical responses. Selective inclusion-complex formation with ferrocenium ions [(P,P)3 -1@Fc(+) ] was confirmed and quantified with HR-ESI-MS and NMR spectroscopy.

Optical and electrochemical properties of spirobifluorene iridanaphthalene complexes.

Three new spirobifluorene iridaaromatic compounds bearing electron-withdrawing or electron-donor substituents or another iridanaphthalene moiety have been synthesized and structurally characterized. Thorough experimental and theoretical evaluation revealed that these novel systems present a high thermal, air and electrochemical stability as well as low optical and electronic energy gap values with a significant redshift of the absorption maximum in the UV-Vis spectra and predicted remarkably higher first hyperpolarizabilities compared to their organic counterparts. Therefore, the combination of a metallaaromatic system with a spirobifluorene moiety leads to the design and development of new spirobifluorene derivatives. These new systems have shown interesting optical and electronic properties making them of interest for future applications in optoelectronics.

ON/OFF Spiroconjugation through Peripheral Functionalization: Impact on the Reactivity and Chiroptical Properties of Spirobifluorenes.

Spirobifluorenes are an important class of spiro compounds frequently used in the field of organic electronics. However, harnessing spiroconjugation to obtain high-performance in such structural motifs remains unexplored. We herein propose that peripheral functionalization may serve as a useful tool to control spiroconjugation in an ON/OFF manner on both chemical reactivity and photophysical properties. In particular, the ratio of mono- and di-functionalized spirobifluorenes found experimentally during their synthesis were found to be 3/2, 7/2, and 12/2 for phenyl, nitro-phenyl and amino-phenyl analogues, respectively. These remarkable reactivity differences correlate with the spiroconjugation character evaluated theoretically at the CAM-B3LYP/6-31G(d,p) level of theory. Additionally, comparison of experimental and predicted optical and chiroptical responses shows that spiroconjugated molecular orbitals have a significant or negligible involvement on the main electronic transitions depending on the peripheral functionality of the spirobifluorene.

Metallaaromatic biaryl atropisomers.

Synthesis of stable irida-binaphthyl and -phenanthryl complexes, the first examples of metallaaromatic biaryl atropisomers, has been achieved. The combination of experimental and theoretical studies revealed that the nature of these systems is comparable to that of well-known 1,1'-binaphthalene both in terms of aromaticity and atropisomerism.

Preparation of 13C4-6-methyl anthranilic ester via a Diels-Alder-type process. an experimental and theoretical study to characterize an unexpected isotope exchange.

Buta-2,3-dienoate reacts with vinyl ketenimine to give the corresponding substituted aniline through a Diels-Alder cycloaddition. Besides the expected Diels-Alder adduct 3a, the aniline 3b was also obtained in a ratio of 91:9. The observed (13)C exchange is explained on the basis of a reversible [2 + 2] cycloaddition competing with the [4 + 2] process. This is supported by B3LYP DFT computations, as a stepwise pathway lies very close in energy to the [4 + 2] concerted one. [reaction: see text]