Effect of Partial Substitution of Zr for Ti Solvent on Young's Modulus, Strength, and Biocompatibility in Beta Ti Alloy.

In orthopedics and dentistry, there is an urgent need to obtain low-stiffness implants that suppress the stress shielding caused by the use of metallic implants. In this study, we aimed to fabricate alloys that can reduce the stiffness by increasing the strength while maintaining a low Young's modulus based on the metastable ß-Ti alloy. We designed alloys in which Ti was partially replaced by Zr based on the ISO-approved metastable ß-Ti alloy Ti-15Mo-5Zr-3Al. All alloys prepared by arc melting and subsequent solution treatment showed a single ß-phase solid solution, with no formation of the ω-phase. The alloys exhibited a low Young's modulus equivalent to that of Ti-15Mo-5Zr-3Al and a high strength superior to that of Ti-15Mo-5Zr-3Al and Ti-6Al-4V. This strengthening was presumed to be due to solid-solution strengthening. The biocompatibility of the alloys was as good as or better than that of Ti-6Al-4V. These alloys have potential as metallic materials suitable for biomedical applications.

Long-term outcomes of additional surgery after endoscopic resection versus primary surgery for T1 colorectal cancer.

INTRODUCTION: There is considerable concern about whether endoscopic resection (ER) prior to additional surgery (AS) for T1 colorectal cancer (CRC) has oncologically potential adverse effects. Therefore, this study aimed to compare the long-term outcomes, including overall survival (OS), of patients treated with AS after ER versus primary surgery (PS) for T1 CRC using a propensity score-matched analysis from a large observational study. METHODS: This study investigated 6105 patients with T1 CRC treated with either ER or surgical resection between 2009 and 2016 at 27 high-volume Japanese institutions, with those undergoing surgery alone included in the PS group and those undergoing AS after ER included in the AS group. Propensity score matching was used for long-term outcomes of mortality and recurrence analysis. RESULTS: After propensity score matching, 1219 of 2438 patients were identified in each group. The 5-year OS rates in the AS and PS groups were 97.1% and 96.0%, respectively (hazard ratio: 0.72, 95% confidence interval [CI]: 0.49-1.08), indicating the non-inferiority of the AS group. Moreover, 32 patients (2.6%) in the AS group and 24 (2.0%) in the PS group had recurrences, with no significant difference between the two groups (odds ratio: 1.34, 95% CI: 0.76-2.40, p = 0.344). DISCUSSION: ER prior to AS for T1 CRC had no adverse effect on patients' long-term outcomes, including the 5-year OS rate. ER is a viable first-line treatment option for endoscopically resectable T1 CRC.

Recent trends in bone metastasis treatments: A historical comparison using the new Katagiri score system.

BACKGROUND: Bone metastasis has various negative impacts. Activities of daily living (ADL) and quality of life (QOL) can be significantly decreased, survival may be impacted, and medical expenses may increase. It is estimated that at least 5% cancer patients might be suffering from bone metastases. In 2016, we published the Comprehensive Guidelines for the Diagnosis and Treatment of Bone Metastasis. Since then, the therapeutic outcomes for patients have gradually improved. As life expectancy is a major determinant of surgical intervention, the strategy should be modified if the prolongation of survival is to be achieved. AIM: To monitor how bone metastasis treatment has changed before and after launch of our guidelines for bone metastasis. METHODS: For advanced cancer patients with bone metastasis who visited the Department of Clinical Oncology at Akita University hospital between 2012 and 2023, parameters including the site and number of bone metastases, laboratory data, and survival time, were extracted from electronic medical records and the Katagiri score was calculated. The association with survival was determined for each factor. RESULTS: Data from 136 patients were obtained. The 1-year survival rate for the poor prognosis group with a higher Katagiri score was 20.0% in this study, which was 6% and an apparent improvement from 2014 when the scoring system was developed. Other factors significantly affecting survival included five or more bone metastases than less (P = 0.0080), and treatment with chemotherapy (P < 0.001), bone modifying agents (P = 0.0175) and immune checkpoint inhibitors (P = 0.0128). In recent years, advances in various treatment methods have extended the survival period for patients with advanced cancer. It is necessary not only to simply extend survival time, but also to maintain ADL and improve QOL. CONCLUSION: Various therapeutic interventions including surgical approach for bone metastasis, which is a disorder of locomotor organs, are increasingly required. Guidelines and scoring system for prognosis need to be revised promptly.

peri-Benzo-Diindenotetracenyl: Helically π-Extended Allyl Radical with Robust Stability.

Here is described the synthesis and characterization of a stable hydrocarbon radical, peri-benzo-diindenotetracenyl, with a helical structure. Although the helical π-radical has no peripheral substituents, it was stable in the solid and solutions. According to the X-ray diffraction analysis and quantum chemical calculations, the radical was best described as an allyl radical fused by five Clar's sextets. The optically resolved enantiomers exhibited mirror image CD spectra with |gCD| of 2.4×10-4 at 522 nm. The racemization barrier was determined to be 95.9 kJ/mol at 298 K, which is compatible with that of [5]helicene (108 kJ/mol).

Optically Distinguishable Electronic Spin-isomers of a Stable Organic Diradical.

Herein, we introduce a model of electronic spin isomers, the electronic counterpart of nuclear spin isomers, by using a stable organic diradical. The diradical, composed of two benzotriazinyl radicals connected by a rigid triptycene skeleton, exhibits a small singlet-triplet energy gap of -3.0 kJ/mol, indicating ca. 1:1 coexistence of the two spin states at room temperature. The diradical shows characteristic near-IR absorption bands, which are absent in the corresponding monoradical subunit. Variable temperature measurements revealed that the absorbance of the NIR band depends on the abundance of the singlet state, allowing us to identify the NIR band as the singlet-specific absorption band. It enables photoexcitation of one of the two spin states coexisting in thermal equilibrium. Transient absorption spectroscopy disclosed that the two spin states independently follow qualitatively different excited-state dynamics. These results demonstrate a novel approach to the design and study of electronic spin isomers based on organic diradicals.

Treatment Decision for Locally Resected T1 Colorectal Carcinoma-Verification of the Japanese Guideline Criteria for Additional Surgery Based on Long-Term Clinical Outcomes.

INTRODUCTION: To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009. METHODS: We enrolled 4,719 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1,259 patients with local resection alone [group A], 1,508 patients with additional surgery after local resection [group B], and 1,952 patients with surgery alone [group C]). All 5 factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively. RESULTS: Any of the risk factors were present in 3,801 patients. The LNM incidence was 10.3% (95% confidence interval 9.3-11.4) in group B/C patients with risk factors, whereas it was 1.8% (95% confidence interval 0.4-5.2) in those without risk factors ( P < 0.01). In group A, the incidence of recurrence was 3.4% in patients with risk factors, but it was only 0.1% in patients without risk factors ( P < 0.01). The disease-free survival rate of group A patients classified as risk positive was significantly worse than those of groups B and C patients. However, the 5-year disease-free survival rate in group A patients with no risk was 99.2%. DISCUSSION: Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM.

Double Negativity of MRI-Detected and Pathologically-Diagnosed Extramural Venous Invasion is a Favorable Prognostic Factor for Rectal Cancer.

BACKGROUND: Extramural venous invasion (EMVI) is a prognostic factor in rectal cancer. There are two types: EMVI detected by magnetic resonance imaging (MRI) (mr-EMVI) and EMVI detected by pathology (p-EMVI). They have been separately evaluated, but they have not yet been concurrently evaluated. We therefore evaluate both mr-EMVI and p-EMVI in rectal cancer at the same time and clarify their association with prognosis. PATIENTS AND METHODS: Included were the 186 consecutive patients who underwent complete radical resection of tumors ≤ stage III at Wakayama Medical University Hospital, Japan, between 2010 and 2018. All underwent preoperative MRI examination, and were reassessed for EMVI by a radiologist. Surgically resected specimens were then reassessed for EMVI by a pathologist. We assessed the correlation between positivity of mr-EMVI and p-EMVI and prognosis, and the clinicopathological background behind them. RESULTS: Patients with double negativity for mr-EMVI and p-EMVI had better prognosis than patients with mr-EMVI or p-EMVI positivity (p < 0.0001). Positivity for mr-EMVI or p-EMVI was a poor independent prognostic factor in multivariate analysis. CONCLUSIONS: Combined analysis of mr-EMVI and p-EMVI may enable prediction of postoperative prognosis of rectal cancer. Patients with double negativity of mr-EMVI and p-EMVI had better prognosis than patients with some form of positivity. Stated differently, patients with positivity of mr-EMVI, p-EMVI, or both had a poorer prognosis than those with double negativity. Postoperative adjuvant chemotherapy may improve poor prognosis. Combined evaluation of mr-EMVI and p-EMVI may be used to predict clinical outcomes and may be an effective prognostic predictor of rectal cancer.

Unified Interpretations of Two Kinds of Needle-Shaped Precipitates Using Transmission Electron Microscopy and Small-Angle Neutron Scattering in Aged Al-Mg2Si(-Cu) Alloys.

This study investigates the nanostructural properties of pseudo-binary Al-1.0Mg2Si (mass%) alloys with and without 0.5Cu using transmission electron microscopy (TEM) and small-angle neutron scattering (SANS). The TEM results show that both alloys exhibit extra electron diffraction spots related to MgSiMg second clusters at peak-aged conditions. High-resolution TEM images have revealed that the second cluster exists as a needle-shaped precipitate that is shorter and thicker than the ß″ phase. We found that the second cluster, which we referred to as the R phase in this paper, is more likely to form partially along the longitudinal axis of a random-type precipitate. Thus, the atomic arrangement in the random-type precipitate is not completely random. SANS is used to quantify the size and volume fraction of the observed needle-shaped precipitates since the R phase is difficult to observe with TEM. The R phase forms even in the Cu-free alloy, but the volume fraction is low, and the growth and formation are retarded near the peak-aged conditions. Undoubtedly, the Cu addition has the effect of stabilizing the growth of the R phase and also promoting its formation. Therefore, the R phase also contributes to the increase in hardness at both under- and peak-aged conditions in the Cu-containing alloy in addition to the strengthening ß″ phases.

How Does Omitting Additional Surgery After Local Excision Affect the Prognostic Outcome of Patients With High-risk T1 Colorectal Cancer?

OBJECTIVE: To investigate how omitting additional surgery after local excision (LE) affects patient outcomes in high-risk T1 colorectal cancer (CRC). BACKGROUND: It is debatable whether additional surgery should be performed for all patients with high-risk T1 CRC regardless of the tolerability of invasive procedures. METHODS: Patients who had received LE for T1 CRC at the Japanese Society for Cancer of the Colon and Rectum institutions between 2009 and 2016 were analyzed. Those who had received additional surgical resection and those who did not were matched one-on-one by the propensity score-matching method. A total of 401 propensity score-matched pairs were extracted from 1975 patients at 27 Japanese Society for Cancer of the Colon and Rectum institutions and were compared. RESULTS: Regional lymph node metastasis was observed in 31 (7.7%) patients in the LE + surgery group. Comparatively, the incidence of oncologic adverse events was low in the LE-alone group, such as the 5-year cumulative risk of local recurrence (4.1%) or overall recurrence (5.5%). In addition, the difference in the 5-year cancer-specific survival between the LE + surgery and LE-alone groups was only 1.8% (99.7% and 97.9%, respectively), whereas the 5-year overall survival was significantly lower in the LE-alone group than in the LE + surgery group [88.5% vs 94.5%, respectively ( P = 0.002)]. CONCLUSIONS: Those who had decided to omit additional surgery at the dedicated center for CRC treatment presented a small number of oncologic events and a satisfactory cancer-specific survival, which may suggest an important role of risk assessment regarding nononcologic adverse events to achieve a best practice for each individual with high-risk T1 tumors.

Lysine-Reactive N-Acyl-N-aryl Sulfonamide Warheads: Improved Reaction Properties and Application in the Covalent Inhibition of an Ibrutinib-Resistant BTK Mutant.

The covalent inhibition of a target protein has gained widespread attention in the field of drug discovery. Most of the current covalent drugs utilize the high reactivity of cysteines toward modest electrophiles. However, there is a growing need for warheads that can target lysine residues to expand the range of covalently druggable proteins and to deal with emerging proteins with mutations resistant to cysteine-targeted covalent drugs. We have recently developed an N-acyl-N-alkyl sulfonamide (NASA) as a lysine-targeted electrophile. Despite its successful application, this NASA warhead suffered from instability in physiological environments, such as serum-containing medium, because of its high intrinsic reactivity. In this study, we sought to modify the structure of the NASA warhead and found that N-acyl-N-aryl sulfonamides (ArNASAs) are promising electrophiles for use in a lysine-targeted covalent inhibition strategy. We prepared a focused library of ArNASA derivatives with diverse structures and reactivity and identified several warhead candidates with suppressed hydrolysis-mediated inactivation and reduced nonspecific reactions with off-target proteins, without sacrificing the reactivity toward the target. These reaction properties enabled the improved covalent inhibition of intracellular heat shock protein 90 (HSP90) in the presence of serum and the development of the first irreversible inhibitor for ibrutinib-resistant Bruton's tyrosine kinase (BTK) bearing the C481S mutation. This study clearly demonstrated the use of a set of ArNASA warheads to create highly potent covalent drugs and highlighted the importance of enriching the current arsenal of lysine-reactive warheads.

Randomized controlled trial comparing cosmetic results of midline incision versus off-midline incision for specimen extraction in laparoscopic colectomy.

PURPOSE: A notable advantage of laparoscopic colorectal surgery is that only a small incision at the extraction site is necessary, which is considered to be cosmetically beneficial. Meanwhile, the optimal extraction site for the resected specimen in laparoscopic colectomy is controversial in terms of cosmetic benefit. This randomized controlled trial compares midline and off-midline extraction sites in laparoscopic colectomy in patients with colon cancer, with consideration of cosmetic benefits as the primary endpoint. METHODS: Included were patients that underwent elective laparoscopic colectomy at WMUH between October 2014 and February 2017. Patients were randomly assigned to either midline incision group or off-midline incision group. Prospectively collected data included cosmetic results (patients and observer assessment scale) and complications including incidence of incisional hernia, SSI, and pain. This trial was registered with UMIN Clinical Trials (UMIN000028943). RESULTS: Finally, 98 patients with colorectal cancer were analyzed. No significant differences were found between the two groups in patient and observer assessment scales of cosmetic results (midline 8 ± 1.1 vs off-midline 11 ± 5.9 p = 0.16, midline 13.5 ± 6.6 vs off-midline 15 ± 11 p = 0.58, respectively) or in postoperative pain. However, incisional hernia occurred in four cases in the midline group (8%), which was significantly higher than that in the off-midline group (no cases, 0%). CONCLUSION: There was no significant difference in terms of cosmetic benefit, the primary endpoint, between the two groups. In this study, only the extraction site location was compared; future studies will examine differences depending on the incisional direction, including the incidence of incisional hernia.

Optimal bowel resection margin in colon cancer surgery: prospective multicentre cohort study with lymph node and feeding artery mapping.

Background: There are no standardised criteria for the 'regional' pericolic node in colon cancer, which represents a major cause of the international uncertainty regarding the optimal bowel resection margin. This study aimed to determine 'regional' pericolic nodes based on prospective lymph node (LN) mapping. Methods: According to preplanned in vivo measurements of the bowel, the anatomical distributions of the feeding artery and LNs were determined in 2996 stages I-III colon cancer patients who underwent colectomy with resection margin >10 cm at 25 institutions in Japan. Findings: The mean number of retrieved pericolic nodes was 20.9 (standard deviation, 10.8) per patient. In all patients except seven (0.2%), the primary feeding artery was distributed within 10 cm of the primary tumour. The metastatic pericolic node most distant from the primary tumour was within 3 cm in 837 patients, 3-5 cm in 130 patients, 5-7 cm in 39 patients and 7-10 cm in 34 patients. Only four patients (0.1%) had pericolic lymphatic spread beyond 10 cm; all of whom had T3/4 tumours accompanying extensive mesenteric lymphatic spread. The location of metastatic pericolic node did not differ by the feeding artery's distribution. Postoperatively, none of the 2996 patients developed recurrence in the remaining pericolic nodes. Interpretation: The pericolic nodes designated as 'regional' were those located within 10 cm of the primary tumours, which should be fully considered when determining the bowel resection margin, even in the era of complete mesocolic excision. Funding: Japanese Society for Cancer of the Colon and Rectum.

Kinetic Analysis of the Photochemical Paths in Asymmetric Diarylethene Dimer.

An asymmetric diarylethene dimer composed of 2- and 3-thienylethene units linked by m-phenylene developed various colors upon UV irradiation via an independent photochromic reaction on each unit. The change in contents and the other photoresponses of the photogenerated four isomers were analyzed using quantum yield for all the possible photochemical paths, i. e., photoisomerization, fluorescence, energy transfer, and the other non-radiative paths. Almost all the rate constants of photochemical paths were calculated using measurable quantum yields and lifetimes. It was found that a significant contribution on photoresponse was the competition between photoisomerization and intramolecular energy transfer. The clear difference was observed in the photoresponses of the dimer and the 1 : 1 mixture solution of the model compounds. The m-phenylene spacer appropriately regulated the rate of energy transfer in the asymmetric dimer, and the spacer enabled isolation of the excited state of the dimer, making the above quantitative analysis possible.

An Investigation of Compressive Creep Aging Behavior of Al-Cu-Li Alloy Pre-Treated by Compressive Plastic Deformation and Artificial Aging.

In this paper, the effects of compressive pre-deformation and successive pre-artificial aging on the compressive creep aging behavior and microstructure evolution of the Al-Cu-Li alloy have been studied. Severe hot deformation mainly occurs near the grain boundaries during the compressive creep initially, which steadily extends to the grain interior. After that, the T1 phases will obtain a low radius-thickness ratio. The secondary T1 phases in pre-deformed samples usually only nucleate on dislocation loops or Shockley incomplete dislocations induced by movable dislocations during creep, which are especially prevalent in low plastic pre-deformation. For all pre-deformed and pre-aged samples, two precipitation situations exist. When pre-deformation is low (3% and 6%), solute atoms (Cu and Li) can be consumed prematurely during pre-aging at 200 °C, with dispersed coherent Li-rich clusters in the matrix. Then, the pre-aged samples with low pre-deformation no longer have the ability to form secondary T1 phases in large quantities during subsequent creep. When dislocation entangles seriously to some extent, a large quantity of stacking faults, together with a "Suzuki atmosphere" containing Cu and Li, can provide the nucleation sites for the secondary T1 phase, even when pre-aged at 200 °C. The sample, pre-deformed by 9% and pre-aged at 200 °C, displays excellent dimensional stability during compressive creep because of the mutual reinforcement of entangled dislocations and pre-formed secondary T1 phases. In order to decrease the total creep strain, increasing the pre-deformation level is more effective than pre-aging.

Elective colorectal cancer surgery in nonagenarians and postoperative outcomes.

OBJECTIVES: The population of very elderly patients is increasing, and nonagenarians have significantly higher mortality rates and poorer rates of survival than younger patients. Meanwhile, recent studies have shown colorectal cancer surgery in nonagenarian patients to be feasible regarding postoperative outcomes. This retrospective study aims to evaluate the postoperative outcomes of nonagenarians in the latest clinical settings. METHODS: Consecutive nonagenarian patients who underwent elective colorectal cancer surgery between 2018 and 2020 retrospectively enrolled (Trial registration number: UMIN000046296 on December 7th, 2021). Clinicopathological data and short-term postoperative outcomes were collected for statistical analysis. RESULTS: This study included 81 nonagenarian patients (31 males, 50 females). Postoperative complications occurred in 21 patients (25.9%), and 3 patients died within 90 days (3.7%). Multivariate analysis revealed prognostic nutritional index was a significant predictor of postoperative complications (OR 2.99, 95% CI 0.78-9.10, P = 0.048), and performance status ≥ 3 could be an independent risk factor of 90-day mortality (HR 32.30, 95% CI 3.20-326.10, P = 0.032). CONCLUSIONS: Short-term outcomes after surgical treatment for nonagenarian patients with colorectal cancer were acceptable. Low prognostic nutritional index was closely related to postoperative complications and poor performance status could also lead to 90-day mortality. In aging populations, risk stratification to prevent poorer postoperative outcomes in nonagenarian patients is needed.

Nomogram as a novel predictive tool for lymph node metastasis in T1 colorectal cancer treated with endoscopic resection: a nationwide, multicenter study.

BACKGROUND AND AIMS: Since 2009, the Japanese Society for Cancer of the Colon and Rectum guidelines have recommended that tumor budding and submucosal invasion depth, in addition to lymphovascular invasion and tumor grade, be included as risk factors for lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC). In this study, a novel nomogram was developed and validated by usirge-scale, real-world data, including the Japanese Society for Cancer of the Colon and Rectum risk factors, to accurately evaluate the risk of LNM in T1 CRC. METHODS: Data from 4673 patients with T1 CRC treated at 27 high-volume institutions between 2009 and 2016 were analyzed for LNM risk. To prepare a nonrandom split sample, the total cohort was divided into development and validation cohorts. Pathologic findings were extracted from the medical records of each participating institution. The discrimination ability was measured by using the concordance index, and the variability in each prediction was evaluated by using calibration curves. RESULTS: Six independent risk factors for LNM, including submucosal invasion depth and tumor budding, were identified in the development cohort and entered into a nomogram. The concordance index was .784 for the clinical calculator in the development cohort and .790 in the validation cohort. The calibration curve approached the 45-degree diagonal in the validation cohort. CONCLUSIONS: This is the first nomogram to include submucosal invasion depth and tumor budding for use in routine pathologic diagnosis based on data from a nationwide multi-institutional study. This nomogram, developed with real-world data, should improve decision-making for an appropriate treatment strategy for T1 CRC.

Thickness profiling of electron transparent aluminium alloy foil using convergent beam electron diffraction.

Convergent beam electron diffraction (CBED) was used to profile the thickness of aluminium alloys foils prepared by using the twinjet electropolishing method. The two-beam CBED condition was obtained by exciting the { 200 } $\{ {200} \}$ and { 111 } $\{ {111} \}$ aluminium diffracted g-vector. The aluminium alloy foil thicknesses were calculated at different distances from the sample hole edge. In areas where only one Kossel-Möllenstedt (K-M) minima fringe was obtained, the thickness was determined by matching the experimental with simulated convergent beam diffraction patterns. In areas far away from the sample edge, the thickness of foils was high enough to generate at least two (K-M) minima fringes, required for linear regression fitting.

All-Visible (>500 nm)-Light-Induced Diarylethene Photochromism Based on Multiplicity Conversion via Intramolecular Energy Transfer.

Photoswitching molecules that reversibly switch upon visible-light irradiation are some of the most attractive targets for biological and imaging applications. In this study, we found a diarylethene (DAE) derivative having a covalently attached perylenebisimide (PBI) unit (DAE-PBI dyad) underwent an unexpected cyclization reaction upon irradiation with green (500-550 nm) light, where the DAE unit has no absorbance. The photoreactivity was enhanced in solvents containing heavy atoms and in the presence of oxygen. As inferred from the solvent dependence and the calculated excited-state energies of DAE and PBI units, it was suggested that the probable mechanism for this unique visible-light-induced cyclization reaction is multiplicity conversion based on intramolecular energy transfer from the excited singlet state of the PBI unit to the triplet state of DAE units (i.e., DAE-1[PBI]* → 3[DAE]*-PBI). Such a unique photoreaction mechanism with the assistance of oxygen will pave the way for new molecular design for the development of visible-light switching molecules.

Heptagon-Embedded π-Expanded Thieno- and N-Methylpyrrolo-Pyridazines with Substantial Out-of-Plane Dipole Moment.

Herein, we describe the synthesis and characterization of fully fused tetraphenylthieno[3,4-d]pyridazine 1 and N-methylpyrrolo[3,4-d]pyridazine 2 with two embedded seven-membered rings. Owing to the incorporated heptagon, 1 and 2 exhibited Cs-symmetric saddle conformations in the solid state with mean plane deviation around 0.38 Å. π-Expanded thienopyridazine 1 showed a one-dimensional (1-D) columnar packing along the b axis with net dipole moment aligning perpendicular to the b axis in the polar crystal system Pc. On the other hand, 2 formed a partially π-stacked brick-work structure. In addition to the Cs-symmetric saddle conformations found in the crystals, density functional theory (DFT) calculation found C2-symmetric twisted conformations of both 1 and 2 close in energy to the saddle conformations. The barrier of conformational interconversion was calculated to be 32 (1) and 31 kJ·mol-1 (2), and the interconversion occurs fast even at -60 °C as evidenced by variable-temperature (VT)-NMR studies. While 1 and 2 have moderately curved structures, optical and electrochemical studies revealed effective π-conjugation over the fused diphenylene units, which is also supported by DFT calculation. As the result of the intrinsic large dipole moment of thieno- and pyrrolo-pyridazines and the notably curved structure, 1 (2) has a substantial out-of-plane dipole moment of 2.0 (3.3) D in the saddle conformations.

π-Expansion of 2,3,6,7-Tetraazanaphthalene with Two Embedded Heptagons: Highly Twisted Structure and Lone-Pair/π* Interaction in the Crystal.

Synthesis and characterization of doubly diphenylene-fused 2,3,6,7-tetraazanaphthalene 1 are described. Single-crystal X-ray diffraction analysis showed the highly twisted structure of 1 with a degree of twisting of 13.0°/Å, which is one of the largest values for a π-system. In the crystal, molecules of 1 formed an orthogonal one-dimensional column with π-stacking of diphenylene moieties and a short intermolecular C···N distance due to lone-pair/π* interaction, which is a rare example of lone-pair/π* interaction in a supramolecular assembly.