Expanding the Frontiers of nail product evaluation: Novel application of differential scanning calorimetry (DSC) for assessing crosslinking density and predicting nail brittleness and flexibility.

OBJECTIVE: While modern industry advancements have expanded nail beautification options, scientific literature primarily focuses on nail biology and medicine, with limited attention on cosmetic treatments. This study aimed to investigate human nail denaturation properties, including gender impact, blending nails to enlarge the sample pool, nail sensitization through bleaching, and active effectiveness testing. The objective was to understand the DSC and bending fatigue relationship, and define the consumer relevance of the DSC test. METHODS: Nail clippings were collected from adult female and male volunteers. The wet DSC was employed to validate sample preparation, explore the effects of gender, and assess the potential of using blended nails for claims substantiation testing. Nails were sensitized through bleaching using hydrogen peroxide. The effects were confirmed through DSC and nail flexure tests. Furthermore, the ability of actives to address concerns related to nail softness and brittleness was assessed using these techniques. RESULTS: The results confirmed the viability of equilibrating nails in water for up to 14 h as a standardized testing method. The denaturation temperature results were independent of gender and suitable for claims substantiation testing. Blending nails from different sources did not yield significant variations in denaturation properties. A preliminary study suggested that cadaver nails should be used with caution because they exhibited differences in denaturation temperature, influenced by the sampling location. Bending fatigue tests highlighted the significance of humidity, with higher humidity conditions (80%) enhancing nail flexibility and providing better resolution for claims substantiation. Sensitizing the nails with hydrogen peroxide induced alterations in both DSC and bending fatigue results. Proof-of-principle studies demonstrated an elevation in denaturation temperature and a decrease in the number of cycles to break, indicating a nail-hardening effect when formaldehyde was applied. The use of a nail softener led to an enhancement in nail fatigue resistance due to a notable reduction in nail crosslinking density. CONCLUSIONS: The measurement of crosslinking density proved to be a sensitive tool for assessing the effects of cosmetic treatments on nails, particularly in predicting outcomes related to nail brittleness and flexibility.

OBJECTIF: Si les progrès de l'industrie moderne ont multiplié les options d'embellissement des ongles, la littérature scientifique se concentre principalement sur la biologie et la médecine des ongles, en portant une attention limitée sur les traitements cosmétiques. Cette étude visait à étudier les propriétés de dénaturation des ongles humains, y compris l'impact en termes de genre, l'uniformisation des ongles pour élargir le pool d'échantillons, la sensibilisation des ongles par le biais d'un blanchiment et les analyses d'efficacité active. L'objectif était de comprendre la relation entre la DSC et la fatigue par flexion, définissant la pertinence du test par DSC pour le consommateur. MÉTHODES: Des coupes d'ongles ont été recueillies auprès de volontaires adultes de sexe féminin et masculin. L'analyse par DSC humide a été utilisée pour valider la préparation des échantillons, étudier les effets en lien avec le genre, et un potentiel d'utilisation d'ongles uniformisés pour les analyses de justification des allégations. Les ongles ont été sensibilisés à l'aide d'un blanchissement au peroxyde d'hydrogène. Les effets ont été confirmés par des analyses par DSC et des tests de flexion des ongles. En outre, la capacité des principes actifs à répondre aux préoccupations liées à la souplesse et à la fragilité des ongles a été évaluée à l'aide de ces techniques. RÉSULTATS: Les résultats ont confirmé la viabilité de l'équilibrage des ongles immergés dans de l'eau pendant une durée maximale de 14 heures comme méthode d'analyse standardisée. Les résultats de la température de dénaturation étaient indépendants du genre et adaptés aux analyses de justification des allégations. L'uniformisation des ongles provenant de différentes sources n'a pas entraîné de variations significatives des propriétés de dénaturation. Une étude préliminaire a suggéré que les ongles prélevés sur des cadavres doivent être utilisés avec prudence, car ils présentaient des différences de température de dénaturation, influencées par le site d'échantillonnage. Les tests de fatigue par flexion ont mis en évidence l'importance de l'humidité, notamment des conditions d'humidité plus élevées (80 %) améliorant la flexibilité de l'ongle et offrant une meilleure résolution pour la justification des allégations. La sensibilisation des ongles avec du peroxyde d'hydrogène a induit des modifications des deux résultats aux analyses par DSC et de fatigue par flexion. Des études de preuve de principe ont démontré une élévation de la température de dénaturation et une diminution du nombre de cycles à rompre, indiquant un effet durcissant de l'ongle lors de l'application de formaldéhyde. L'utilisation d'un émollient unguéal a permis d'améliorer la résistance à la fatigue des ongles en raison d'une réduction notable de la densité de réticulation des ongles. CONCLUSIONS: La mesure de la densité de réticulation s'est avérée être un outil sensible pour évaluer les effets des traitements cosmétiques sur les ongles, en particulier pour prédire les résultats liés à la fragilité et à la flexibilité des ongles.

The gut-lung axis in critical illness: microbiome composition as a predictor of mortality at day 28 in mechanically ventilated patients.

BACKGROUND: Microbial communities are of critical importance in the human host. The lung and gut microbial communities represent the most essential microbiota within the human body, collectively referred to as the gut-lung axis. However, the differentiation between these communities and their influence on clinical outcomes in critically ill patients remains uncertain. METHODS: An observational cohort study was obtained in the intensive care unit (ICU) of an affiliated university hospital. Sequential samples were procured from two distinct anatomical sites, namely the respiratory and intestinal tracts, at two precisely defined time intervals: within 48 h and on day 7 following intubation. Subsequently, these samples underwent a comprehensive analysis to characterize microbial communities using 16S ribosomal RNA (rRNA) gene sequencing and to quantify concentrations of fecal short-chain fatty acids (SCFAs). The primary predictors in this investigation included lung and gut microbial diversity, along with indicator species. The primary outcome of interest was the survival status at 28 days following mechanical ventilation. RESULTS: Sixty-two mechanically ventilated critically ill patients were included in this study. Compared to the survivors, the diversity of microorganisms was significantly lower in the deceased, with a significant contribution from the gut-originated fraction of lung microorganisms. Lower concentrations of fecal SCFAs were detected in the deceased. Multivariate Cox regression analysis revealed that not only lung microbial diversity but also the abundance of Enterococcaceae from the gut were correlated with day 28 mortality. CONCLUSION: Critically ill patients exhibited lung and gut microbial dysbiosis after mechanical ventilation, as evidenced by a significant decrease in lung microbial diversity and the proliferation of Enterococcaceae in the gut. Levels of fecal SCFAs in the deceased served as a marker of imbalance between commensal and pathogenic flora in the gut. These findings emphasize the clinical significance of microbial profiling in predicting the prognosis of ICU patients.

Acute pancreatitis: A review of diagnosis, severity prediction and prognosis assessment from imaging technology, scoring system and artificial intelligence.

Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease of the pancreas, with clinical management determined by the severity of the disease. Diagnosis, severity prediction, and prognosis assessment of AP typically involve the use of imaging technologies, such as computed tomography, magnetic resonance imaging, and ultrasound, and scoring systems, including Ranson, Acute Physiology and Chronic Health Evaluation II, and Bedside Index for Severity in AP scores. Computed tomography is considered the gold standard imaging modality for AP due to its high sensitivity and specificity, while magnetic resonance imaging and ultrasound can provide additional information on biliary obstruction and vascular complications. Scoring systems utilize clinical and laboratory parameters to classify AP patients into mild, moderate, or severe categories, guiding treatment decisions, such as intensive care unit admission, early enteral feeding, and antibiotic use. Despite the central role of imaging technologies and scoring systems in AP management, these methods have limitations in terms of accuracy, reproducibility, practicality and economics. Recent advancements of artificial intelligence (AI) provide new opportunities to enhance their performance by analyzing vast amounts of clinical and imaging data. AI algorithms can analyze large amounts of clinical and imaging data, identify scoring system patterns, and predict the clinical course of disease. AI-based models have shown promising results in predicting the severity and mortality of AP, but further validation and standardization are required before widespread clinical application. In addition, understanding the correlation between these three technologies will aid in developing new methods that can accurately, sensitively, and specifically be used in the diagnosis, severity prediction, and prognosis assessment of AP through complementary advantages.

Prognostic value of platelet combined with serum procalcitonin in patients with sepsis.

Sepsis, a common and life-threatening condition in critically ill patients, is a leading cause of death in intensive care units. Over the past few decades, there has been significant improvement in the understanding and management of sepsis. However, the mortality rate remains unacceptably high, posing a prominent challenge in modern medicine and a significant global disease burden. A total of 295 patients with sepsis admitted to the hospital from January 2021 to December 2022 were collected and divided into survival group and death group according to their 28-day survival status. The differences in general clinical data and laboratory indicators between the 2 groups were compared. Receiver operating characteristic curve analysis was used to evaluate the predictive value of platelet (PLT) and procalcitonin (PCT) for the prognosis of sepsis patients within 28 days. A total of 295 patients were diagnosed with sepsis, and 79 died, with a mortality rate of 26.78%. The PLT level in the death group was lower than that in the survival group; the PCT level in the death group was higher than that in the survival group. The receiver operating characteristic curve showed that the area under the curve of PCT and PLT for evaluating the prognosis of sepsis patients were 0.808 and 0.804, respectively. Kaplan-Meier survival analysis showed that the 28-day survival rate of the low PLT level group was 19.0% and that of the high PLT level group was 93.1% at the node of 214.97 × 109/L, and the difference between the 2 groups was statistically significant (χ2 = 216.538, P < .001). The 28-day survival rate of the low PCT level group was 93.4% and that of the high PCT level group was 51.7% at the node of 2.85 ng/mL, and the difference between the 2 groups was statistically significant (χ2 = 63.437, P < .001). There was a negative correlation between PCT level and PLT level (r = -0.412, P < .001). Platelet combined with serum procalcitonin detection has high predictive value for judging the 28-day prognosis of sepsis, and it can be used as an index for evaluating the patient's condition and prognosis, and is worthy of clinical promotion and application.

Decoding the biological properties and transcriptomic landscapes of human natural killer cells derived from bone marrow and umbilical cord blood.

Longitudinal studies have highlighted allogeneic natural killer (NK) cell-based cytotherapy for cancer immunosurveillance and immunotherapy, yet the deficiency of systematic and detailed comparison of NK cells from candidate sources including umbilical cord blood (UC) and bone marrow (BM) largely hinders the large-scale application. Herein, we isolated resident NK cells (rUC-NK, rBM-NK) from mononuclear cells (MNC), and analyzed the corresponding expanded NK cell counterparts (eUC-NK, eBM-NK). Then, the eUC-NK and eBM-NK were turned to multifaceted bioinformatics from the aspects of gene expression profiling and genetic variations. The percentages of total or activated NK cells in rBM-NK group were approximate 2-fold higher over those in the rUC-NK group, respectively. Instead, the proportion of total NK cells in eUC-NK was higher than that in the eBM-NK group, and in particular, the CD25+ memory-like NK cell subset. Furthermore, eUC-NK and eBM-NK manifested multidimensional similarities and diversities in gene expression pattern and genetic spectrum, whereas both eUC-NK and eBM-NK exhibited effective tumor killing capacity. Collectively, we dissected the cellular and transcriptomic signatures of NK cells generated from UC-MNC and BM-MNC, which supplied new literature for further exploring the characteristics of the indicated NK cells and would benefit the clinical application for cancer immunotherapy in future.

Efficacy and safety of COVID-19 vaccines: a systematic review.

OBJECTIVE: To evaluate systematically the efficacy and safety of COVID-19 vaccines. METHODS: PubMed, Embase, Cochrane Library, Clinicaltrial.gov, CNKI, Wanfang Data, China Biomedical Literature Service System, and China Clinical Trial Registry were searched for randomized controlled trials of COVID-19 vaccines published up to December 31, 2020. The Cochrane bias risk assessment tool was used to assess the quality of studies. A qualitative analysis was performed on the results of clinical trials. RESULTS: Thirteen randomized, blinded, controlled trials, which involved the safety and efficacy of 11 COVID-19 vaccines, were included. In 10 studies, the 28-day seroconversion rate of subjects exceeded 80%. In two 10 000-scale clinical trials, the vaccines were effective in 95% and 70.4% of the subjects, respectively. The seroconversion rate was lower than 60% in only one study. In six studies, the proportion of subjects who had an adverse reaction within 28 days after vaccination was lower than 30%. This proportion was 30%-50% in two studies and > 50% in the other two studies. Most of the adverse reactions were mild to moderate and resolved within 24 hours after vaccination. The most common local adverse reaction was pain or tenderness at the injection site, and the most common systemic adverse reaction was fatigue, fever, or bodily pain. The immune response and incidence of adverse reactions to the vaccines were positively correlated with the dose given to the subjects. The immune response to the vaccines was worse in the elderly than in the younger population. In 6 studies that compared single-dose and double-dose vaccination, 4 studies showed that double-dose vaccination produced a stronger immune response than single-dose vaccination. CONCLUSIONS: Most of the COVID-19 vaccines appear to be effective and safe. Double-dose vaccination is recommended. However, more research is needed to investigate the long-term efficacy and safety of the vaccines and the influence of dose, age, and production process on the protective efficacy.

A case of bi-ventricular extensive calcification caused by multiple factors.

BACKGROUND: Extensive myocardial calcification has a low incidence rate, but when the patients do have extensive myocardial cases, the prognosis is usually poor. Several sepsis-related extensive myocardial calcification cases have been reported, but there are cases of biventricular calcifications that are caused by multiple cases besides bacteremia and the treatment for it has a low percentage of success. CASE PRESENTATION: A 9 year old girl had an extensive biventricular calcification which is caused by multiple factors including multiple organ failure (heart, lung, liver, and kidney), aseptic cardiomyopathy, systemic inflammatory response syndrome, pulmonary hemorrhage, viral encephalitis. In this case study, the massive myocardial calcification present in the patient was classified as dystrophic. After the patient was transferred to the Intensive care unit, a series of rescue treatments such as anti-inflammatory factor storm were implemented to protect the organs. In the end, the patient was rescued from the rescue treatment procedure. After 18 months of follow-up, it was observed that the patient's heart function returned to normal and it was observed that there was no change in myocardial calcification in the patient. CONCLUSION: In this case study, it showcased a case of the diffused biventricular calcification that caused by multiple factors. Furthermore, the precise role of calcification on cardiac function was largely unknown and there has to be further follow-up observation on the patient.

Fabrication of Reduction-Sensitive Amphiphilic Cyclic Brush Copolymer for Controlled Drug Release.

The cyclic brush polymers, due to the unique topological structure, have shown in the previous studies higher delivery efficacy than the bottlebrush analogues as carriers for drug and gene transfer. However, to the best of knowledge, the preparation of reduction-sensitive cyclic brush polymers for drug delivery applications remains unexplored. For this purpose, a reduction-sensitive amphiphilic cyclic brush copolymer, poly(2-hydroxyethyl methacrylate-g-poly(ε-caprolactone)-disulfide link-poly(oligoethyleneglycol methacrylate)) (P(HEMA-g-PCL-SS-POEGMA)) with reducible block junctions bridging the hydrophobic PCL middle layer and the hydrophilic POEGMA outer corona is designed and synthesized successfully in this study via a "grafting from" approach using sequential ring-opening polymerization (ROP) and atom transfer free radical polymerization (ATRP) from a cyclic multimacroinitiator PHEMA. The resulting self-assembled unimolecular core-shell-corona (CSC) micelles show sufficient salt stability and efficient destabilization in the intracellular reducing environment for a promoted drug release toward a greater therapeutic efficacy relative to the reduction-insensitive analogues. The overall results demonstrate the reducible cyclic brush copolymers developed herein provides an elegant solution to the tradeoff between extracellular stability and intracellular high therapeutic efficacy toward efficient anticancer drug delivery.

Fabrication of Thermosensitive Cyclic Brush Copolymer with Enhanced Therapeutic Efficacy for Anticancer Drug Delivery.

Adaptation of cyclic brush polymer for drug delivery applications remains largely unexplored. Herein, cyclic brush copolymer of poly(2-hydroxyethyl methacrylate-g-poly(N-isopropylacrylamide-st-N-hydroxyethylacrylamide)) (cb-P(HEMA-g-P(NIPAAm-st-HEAAm))), comprising a cyclic core of PHEMA and thermosensitive brushes of statistical copolymer of P(NIPAAm-st-HEAAm), is designed and synthesized successfully via a graft-from approach using atom transfer free radical polymerization from a cyclic multimacroinitiator. The composition of the brush is optimized to endow the resulting cyclic brush copolymer with a lower critical solution temperature (LCST) slightly above the physiological temperature, but lower than the localized temperature of tumor tissue, which is suitable for the hyperthermia-triggered anticancer drug delivery. Critical aggregation concentration determination reveals better stability for the unimolecular nanoparticle formed by the cyclic brush copolymer than that formed by the bottlebrush analogue. The dramatically increased size with elevated temperatures from below to above the LCST confirms hyperthermia-induced aggregation for both formulations. Such structural destabilization promotes significantly the drug release at 40 °C. Most importantly, the drug-loaded cyclic brush copolymer shows enhanced in vitro cytotoxicity against HeLa cells than the bottlebrush counterpart. The better stability and higher therapeutic efficacy demonstrates that the thermosensitive cyclic brush copolymer is a better formulation than bottle brush copolymer for controlled drug release applications.

Synthesis and Phase Transition of Poly(N-isopropylacrylamide)-Based Thermo-Sensitive Cyclic Brush Polymer.

Polymers with advanced topological architectures are promising materials for wide applications due to their structure-generated unique properties different from that of the linear analogues. The elegant integration of stimuli-responsive polymers with such advanced architectures can create novel materials with virtues from both moieties, are thus a hot subject of research for both fundamental and practical investigations. To fabricate cyclic brush polymer-based intelligent materials for biomedical applications, herein, we designed and synthesized thermo-sensitive cyclic brush polymers with poly(N-isopropylacrylamide) (PNIPAAm) brushes by controlled living radical polymerization using cyclic multimacroinitiator. The thermo-induced phase transition behaviors of the resultant cyclic brush polymers with different compositions were investigated in detail by temperature-dependent optical transmittance measurements, and compared with the properties of bottlebrush and linear counterparts. Interestingly, the cloud point transition temperature (Tcp) of cyclic brush PNIPAAm could be regulated by the chain length of PNIPAAm brush. Although the bottlebrush polymers with the same composition exhibited similarly structurally dependent Tcps behaviors to the cyclic brush polymers, the cyclic brush PNIPAAm did show higher critical aggregation concentration (CAC) and enhanced stability against dilution than the bottlebrush counterpart. The readily tailorable Tcps together with the ability to form highly stable nanoparticles makes thermo-sensitive cyclic brush PNIPAAm a promising candidate for controlled drug delivery.

Synthesis of [closo-B12(OH)11NH3]-: a new heterobifunctional dodecaborane scaffold for drug delivery applications.

Effective utilization of [closo-B12H12](2-) derivatives in targeted drug delivery applications depends upon an efficient strategy to differentiate at least one of the 12 vertices on the B12(2-) core. Precursor molecules must also be able to withstand the initial harsh hydrogen peroxide treatment necessary for hydroxylation of the B-H vertices. We report here a method for preparation of the ammonio derivative [closo-B12(OH)11NH3](-) and also demonstrate its utility in construction of a targeted drug delivery scaffold. Treatment of the precursor [closo-B12H11NH3](-) with hydrogen peroxide gives the corresponding nitro derivative [closo-B12(OH)11NO2](2-) in good yield. The nitro group is easily reduced with hydrogen over a Raney nickel catalyst to produce [closo-B12(OH)11NH3](-). The 11 hydroxyl groups can then be readily converted to carbonates or carbamates. As a proof-of-principle of its utility as a drug delivery system, we used the resulting vertex-differentiated ammonio derivative to construct a platinated pro-drug possessing 11 copies of a carboplatin analogue conjugated to the B12(2-) core via carbamate linkage and a fluorescein molecule attached at the remaining vertex by an amide linkage. In vitro cytotoxicity assays demonstrated that activity of an untagged analog was similar to carboplatin against platinum-sensitive A459 cells and higher than carboplatin against platinum-resistant SK-OV-3 cells. Further fluorescence microscopy revealed that the fluorescein-tagged pro-drug localizes to the nuclei of A459 cells.

Geometrically specific imino complexes of the [Re6(µ3-Se)8]2+ core-containing clusters.

The reactions of nitrile complexes of the [Re(6)(µ(3)-Se)(8)](2+) core-containing clusters, [Re(6)(µ(3)-Se)(8)(PEt(3))(n)(CH(3)CN)(6-n)](2+) [n = 5 (1); n = 4, cis- (2) and trans- (3); n = 0 (4)], with organic azides C(6)H(5)CH(CH(3))N(3) and C(6)H(5)CH(2)N(3) produced the corresponding cationic imino complexes of the general formula [Re(6)(µ(3)-Se)(8)(PEt(3))(n)(L)(6-n)](2+) [L = PhN=CHCH(3): n = 5 (5); n = 4, cis- (6) and trans- (7); n = 0 (8) and L = HN=CHPh: n = 5 (9); n = 4, cis- (10) and trans- (11)]. These novel complexes were characterized by NMR spectroscopy ((1)H and (31)P) and single-crystal X-ray diffraction. A mechanism involving the migration of one of the groups on the azido α-C atom to the α-N atom of the azido complex, concerted with the photo-expulsion of N(2), was invoked to rationalize the formation of the imino complexes. Density functional theory (DFT) calculations indicated that due to the coordination with and activation by the cluster core, the energy of the electronic transition responsible for the photo-decomposition of a cluster-bound azide is much reduced with respect to its pure organic counterpart. The observed geometric specificity was rationalized by using the calculated and optimized preferred ground-state conformation of the cluster-azido intermediates.

An electrochemical and photophysical study of a covalently linked inorganic-organic dyad.

A molecular donor-acceptor dyad comprising a hexarhenium cluster core, [Re(6)(mu(3)-Se)(8)](2+), and a fullerene moiety which are covalently linked through a pyridine ligand was synthesized and fully characterized. The electrochemical and photophysical properties are reported. The detailed study includes cyclic voltammetry, steady-state absorption and fluorescence spectroscopy, radiation chemistry and transient absorption spectroscopy. A light-induced electron transfer between the inorganic cluster moiety and the fullerene can be excluded. However, a light-induced energy transfer from the rhenium cluster to the fullerene is proposed.

Cluster-bound nitriles do not click with organic azides: unexpected formation of imino complexes of the [Re(6)(mu(3)-Se)(8)](2+) core-containing clusters.

The reactions of C(6)H(5)CH(CH(3))N(3) with nitrile solvates of the [Re(6)(mu(3)-Se)(8)](2+) core-containing cluster, [Re(6)(mu(3)-Se)(8)(PEt(3))(5)(MeCN)](2+)(1) and cis-[Re(6)(mu(3)-Se)(8)(PEt(3))(4)(MeCN)(2)](2+) (2), afforded the corresponding cationic imino complexes [Re(6)(mu(3)-Se)(8)(PEt(3))(5)(PhN horizontal lineCHCH(3))](2+) (3) and cis-[Re(6)(mu(3)-Se)(8)(PEt(3))(4)(PhN horizontal lineCHCH(3))(2)](2+) (4), respectively. Both compounds were spectroscopically and crystallographically characterized. A mechanism involving a 1,2-shift of one of the groups on the azido alpha-C atom of the cluster-azide intermediate concerted with the photoexpulsion of dinitrogen of the azido ligand is invoked to rationalize the formation of the imino complexes. Density functional theory calculations showed that a cluster-to-ligand transition was responsible for the absorption that promotes the photodecomposition of the cluster-azide complex.

Complexes of the [Re(6)(mu(3)-Se)(8)](2+) core-containing clusters with the water-soluble 1,3,5-triaza-7-phosphaadamantane (PTA) ligand: unexpected ligand protonation and related studies.

Three new complexes of the [Re(6)(mu(3)-Se)(8)](2+) core-containing clusters with the water-soluble trialkylphosphine ligand 1,3,5-triaza-7-phosphaadamantane (PTA), [Re(6)(micro(3)-Se)(8)(PEt(3))(5)(PTA)](SbF(6))(2) (P5PTA, ), [Re(6)(micro(3)-Se)(8)(PEt(3))(5)(PTAH)][Re(6)(micro(3)-Se)(8)(PEt(3))(5)(PTA)](SbF(6))(5) (), and [Re(6)(micro(3)-Se)(8)(PEt(3))(5)(PTAH)](2)(HBr)(SbF(6))(2)Br(4) () have been prepared and structurally characterized. Unexpected protonation of the cluster-bound PTA ligand was observed when coordination of with HgI(2) was attempted, affording compound featuring a protonated PTA ligand, PTAH. Deliberate acidification of with HBr produced compound , and the protonation was investigated by using (31)P NMR spectroscopy. Crystallographic studies revealed distinct structural distortions of the ligand as a result of protonation.