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Abstract Background Lipodystrophy is a relatively rare, complex disease characterised by a deficiency of adipose tissue and can present as either generalised lipodystrophy (GLD) or partial lipodystrophy (PLD). The prevalence of this disease varies by region. This study aimed to identify the genetic variations associated with lipodystrophy in the southern part of Saudi Arabia. Methodology We conducted a retrospective study by recruiting nine patients from six families, recruiting the proband whole exome sequencing results or any other genetic test results, screening other family members using Sanger sequencing and analysing the carrier status of the latter. These patients were recruited from the Endocrinology and Diabetes Clinic at Jazan General Hospital and East Jeddah Hospital, both in the Kingdom of Saudi Arabia. Result Eight patients were diagnosed with GLD, and one was diagnosed with PLD. Of the six families, four were consanguineously married from the same tribe, while the remaining belonged to the same clan. The majority of GLD patients had an AGPAT2 c.158del mutation, but some had a BSCL2 c.942dup mutation. The single PLD case had a PPARG c.1024C > T mutation but no family history of the disease. In all families evaluated in this study, some family members were confirmed to be carriers of the mutation observed in the corresponding patient. Conclusion Familial screening of relatives of patients with rare, autosomal recessive diseases, such as lipodystrophy, especially when there is a family history, allows the implementation of measures to prevent the onset or reduced severity of disease and reduces the chances of the pathogenic allele being passed onto future generations. Creating a national registry of patients with genetic diseases and carriers of familial pathogenic alleles will allow the assessment of preventive measures and accelerate disease intervention via gene therapy.

Exam timetabling is a prominent topic in academic administration management as it ensures the effective utilization of resources and satisfies the requirements and preferences of stakeholders, which leads to a productive academic environment, contributing to the institution’s overall success. Given the myriad of solution methodologies explored across diverse exam timetabling problems and constraints, both in studied benchmark datasets and real-life cases over the last decade, it is imperative to undertake a comprehensive survey. This survey paper aims to comprehensively describe the exam timetabling problem (ETP), including its variants, constraints, and benchmark dataset. We look at different methods to solve ETP problems from 2012 to 2023. These methods include mathematical optimization, heuristics, metaheuristics, hyper-heuristics, hybrid approaches, and matheuristics. Finally, we discuss the review findings and potential research directions. By doing so, we hope to facilitate a deeper understanding of ETP and offer valuable insights for future research.

Abstract Background Soil salinity is one of the most important factors limiting crop production. Furthermore, with the increasing population and saline soil worldwide there is no choice but to utilize saline soil to increase the agricultural regions. Therefore, to improve carrot productivity under saline conditions, it is necessary to provide good management such as applying hydrogels and biochar for improving soil properties. Methodology Hydrogels (PEtOx-HEMA-CS) were synthesized from poly (2-ethyl-2-oxazoline), 2-hydroxyethyl methacrylate (HEMA as crosslinker) and chitosan (CS) via exposure those to gamma irradiation dose; 30 kGy of dose rate 0.9 kGy/h and obtained three types of hydrogels according to concentration of chitosan used. The PEtOx-HEMA-CS hydrogels were enhanced water holding capacity for agriculture purposes. The chemical structures of obtained hydrogels were characterized by FTIR, XRD and SEM. The swelling (%) and gelation (%) were determined. Biochar (BC) as an active substance was physically mixed with those hydrogels at various ratios (0/100, 0.5/99.5, 1/99 and 100/0 (g/g) biochar/hydrogels). BC, PEtOx-HEMA-CS and the mixture of PEtOx-HEMA-CS-BC were mixed with saline soil at ratio 0.05% and 0.1% w/w of obtained materials/soil. A pot experiment was conducted to mitigate the salinity hazards on carrot productivity using biochar with and without hydrogels. Mean maximum temperature, minimum temperature, precipitation, relative humidity and wind speed from September to December in the studied region are 28.66 ℃, 15.76 ℃, 0.01 mm, 58.81%, 5.94 km/h, respectively. Findings The obtained data referred that there is a significant decrease in soil salinity and exchangeable sodium percentage and increase in organic matter, cation exchange capacity, field capacity, permanent wilting point and available water especially at (PEtOx-HEMA-CS5)0.1-BC1. The highest increment percentage of nitrogen, phosphorous and potassium were 36.36%, 70% and 72%, respectively. In addition, the relative increase of carrot productivity was 49.63% at the highest rates of biochar and hydrogels. However, the highest value of water use efficiency was observed at the mixture of biochar and hydrogels at (PEtOx-HEMA-CS5)0.1-BC1. Conclusions Finally, applying biochar combined with (PEtOx-HEMA-CS5) could be recommended as a good approach to improve carrot productivity and water use efficiency under saline soil conditions. Graphical Abstract

This survey paper provides an overview of current developments for the Portfolio Optimisation Problem (POP) based on articles published from 2018 to 2022. It reviews the latest solution methodologies utilised in addressing POPs in terms of mechanisms and performance. The methodologies are categorised as Metaheuristic, Mathematical Optimisation, Hybrid Approaches, Matheuristic and Machine Learning. The datasets (benchmark, real-world, and hypothetical) utilised in portfolio optimisation research are provided. The state-of-the-art methodologies for benchmark datasets are presented accordingly. Population-based metaheuristics are the most preferred techniques among researchers in addressing the POP. Hybrid approaches is an emerging trend (2018 onwards). The OR-Library is the most widely used benchmark dataset for researchers to compare their methodologies in addressing POP. The research challenges and opportunities are discussed. The summarisation of the published papers in this survey provides an insight to researchers in identifying emerging trends and gaps in this research area.

This paper presents an overview of recent advances for the Nurse Rostering Problem (NRP) based on methodological papers published between 2012 to 2021. It provides a comprehensive review of the latest solution methodologies, particularly computational intelligence (CI) approaches, utilized in benchmark and real-world nurse rostering. The methodologies are systematically categorised (Heuristics, Meta-heuristics, Hyper-heuristics, Mathematical Optimisation, Matheuristics and Hybrid Approaches). The NRP benchmark repositories and the respective state-of-the-art methods are also presented. A distinctive feature of this survey is its focus on the emerging trends in terms of solution methodologies and benchmark datasets. Meta-heuristics are the most popular choices in addressing NRP. Matheuristics, one of most popular methodologies in addressing the NRP, has been an emerging trend in recent years (2018 onwards). The INRC-I dataset is the most popular benchmark currently in use by researchers to test their algorithms. An in-depth discussion on the challenges and research opportunities is provided. The summary and analysis of the recently published NRP methodological papers in this survey is valuable for the CI and Operational Research (OR) communities especially early career researchers seeking to find gaps and identify emerging trends in this fast-developing, important research area.

In this paper, we are addressing the NP-hard nurse rostering problem utilizing a 2-stage approach. In stage one, Monte Carlo Tree Search (MCTS) and Hill Climbing (HC) are hybridized in finding a feasible solution (satisfying all the hard constraints). We propose a new constant $C$ value (which balances search diversification and intensification of MCTS) and tree policy/node selection function in the selection procedure of MCTS. In stage two, the feasible solution is further improved using Iterated Local Search (ILS) with Variable Neighbourhood Descent as the local search component. We introduce several unique neighbourhood structures for the ILS. In addition, we propose a novel perturbation strategy to allow the search to escape from local optimum. The proposed methodology is tested on the Shift Scheduling dataset (24 benchmark instances). New best results are reported for seven and two instances for the 10 and 60 minutes run respectively. An in-depth discussion on the attributes of the proposed methodology that lead to its good performance is provided.

Smart meters allow real-time monitoring and collection of power consumption data of a consumer's premise. With the worldwide integration of smart meters, there has been a substantial rise in concerns regarding threats to consumer privacy. The exposed fine-grained power consumption data results in behaviour leakage by revealing the end-user's home appliance usage information. Previously, researchers have proposed approaches to alter data using perturbation, aggregation or hide identifiers using anonymization. Unfortunately, these techniques suffer from various limitations. In this paper, we propose a privacy preserving architecture for fine-grained power data in a smart grid. The proposed architecture uses generative adversarial network (GAN) and an obfuscator to generate a synthetic timeseries. The proposed architecture enables to replace the existing appliance signature with appliances that are not active during that period while ensuring minimum energy difference between the ground truth and the synthetic timeseries. We use real-world dataset containing power consumption readings for our experiment and use non-intrusive load monitoring (NILM) algorithms to show that our approach is more effective in preserving the privacy level of a consumer's power consumption data.

This article addresses a challenging industrial problem known as the unrelated parallel machine scheduling problem (UPMSP) with sequence-dependent setup times. In UPMSP, we have a set of machines and a group of jobs. The goal is to find the optimal way to schedule jobs for execution by one of the several available machines. UPMSP has been classified as an NP-hard optimisation problem and, thus, cannot be solved by exact methods. Meta-heuristic algorithms are commonly used to find sub-optimal solutions. However, large-scale UPMSP instances pose a significant challenge to meta-heuristic algorithms. To effectively solve a large-scale UPMSP, this article introduces a two-stage evolutionary variable neighbourhood search (EVNS) methodology. The proposed EVNS integrates a variable neighbourhood search algorithm and an evolutionary descent framework in an adaptive manner. The proposed evolutionary framework is employed in the first stage. It uses a mix of crossover and mutation operators to generate diverse solutions. In the second stage, we propose an adaptive variable neighbourhood search to exploit the area around the solutions generated in the first stage. A dynamic strategy is developed to determine the switching time between these two stages. To guide the search towards promising areas, a diversity-based fitness function is proposed to explore different locations in the search landscape. We demonstrate the competitiveness of the proposed EVNS by presenting the computational results and comparisons on the 1640 UPMSP benchmark instances, which have been commonly used in the literature. The experiment results show that our EVNS obtains better results than the compared algorithms on several UPMSP instances.

The timetabling problem is common to academic institutions such as schools, colleges or universities. It is a very hard combinatorial optimisation problem which attracts the interest of many researchers. The university course timetabling problem (UCTTP) is difficult to address due to the size of the problem and several challenging hard and soft constraints. Over the years, various methodologies were proposed to solve UCTTP. The purpose of this survey paper is to provide the most recent scientific review of the methodologies applied to UCTTP. The paper unveils a classification of methodologies proposed in recent years based on chronology and datasets used. Perspectives, trends, challenges and opportunities in UCTTP are also presented. It is observed that meta-heuristic approaches are popular among researchers. This is followed closely by hybrid methodologies. Hyper-heuristic approaches are also able to produce effective results. Another observation is that the state-of-art methodologies in the scientific literature are not fully utilised in a real-world environment perhaps due to the limited flexibility of these methodologies.

Background: Medication-related osteonecrosis of the jaw (MRONJ) is an intense negative drug response causing increasing bone destruction in the maxillofacial area of patients. Aims and Objectives: To evaluate the knowledge and attitude of dental practitioner regarding risk factors of MRONJ in Saudi Arabia. Materials and Methods: A cross-sectional, questionnaire survey was carried out in King Khalid Hospital, Al-Kharj among dental practioners. Results: Approximately 60% of the practioners had a poor knowledge and there was a weak positive correlation with work experience. Conclusion: Poor knowledge regarding the MRONJ invites a continuing dental education specially to focus on general practioners.

Carob-mediated calcium hydroxide nanoparticles (C-CaOH2 NPs) are a type of NPs, newly developed via a green synthesis method, that have demonstrated good in vitro biocompatibility. However, their antibacterial potential has not yet been explored. Both calcium hydroxide and carob are known for their antibacterial potency as bulk materials; thus, we hypothesized that C-CaOH2 NPs may exhibit promising antibacterial efficacy. This study aimed to examine the antibacterial activity of C-CaOH2 NPs against aerobic and anaerobic strains using zone of inhibition (ZOI), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) tests. The results showed that the Gram-negative aerobic strains are more susceptible than the Gram-positive stains. The most susceptible bacteria were P. aeruginosa, E. coli, and S. aureus, in that order. Conversely, P. micra and E. faecalis were the least susceptible strains. The best recorded ZOIs were at 100 and 150 mg/mL concentrations in all bacteria, with the greatest diameter (11.7 ± 0.6 mm) exhibited in P. aeruginosa. Moreover, the MICs for aerobes were 3.12 mg/mL, except for E. faecalis (0.78 mg/mL) and K. pneumoniae (1.56 mg/mL). MBCs were 12.5 mg/mL for all except P. aeruginosa (3.12 mg/mL) and K. pneumoniae (6.25 mg/mL). The anaerobic strain P. micra exhibited the highest values for both MIC (15.62 mg/mL) and MBC (31.25 mg/mL). The current investigation revealed that C-CaOH2 NPs have intermediate and dose-dependent antibacterial activity that may have variable biomedical applications.

Cyber security in the context of big data is known to be a critical problem and presents a great challenge to the research community. Machine learning algorithms have been suggested as candidates for handling big data security problems. Among these algorithms, support vector machines (SVMs) have achieved remarkable success on various classification problems. However, to establish an effective SVM, the user needs to define the proper SVM configuration in advance, which is a challenging task that requires expert knowledge and a large amount of manual effort for trial and error. In this paper, we formulate the SVM configuration process as a bi-objective optimization problem in which accuracy and model complexity are considered as two conflicting objectives. We propose a novel hyper-heuristic framework for bi-objective optimization that is independent of the problem domain. This is the first time that a hyper-heuristic has been developed for this problem. The proposed hyper-heuristic framework consists of a high-level strategy and low-level heuristics. The high-level strategy uses the search performance to control the selection of which low-level heuristic should be used to generate a new SVM configuration. The low-level heuristics each use different rules to effectively explore the SVM configuration search space. To address bi-objective optimization, the proposed framework adaptively integrates the strengths of decompositionand Paretobased approaches to approximate the Pareto set of SVM configurations. The effectiveness of the proposed framework has been evaluated on two cyber security problems: Microsoft malware big data classification and anomaly intrusion detection. The obtained results demonstrate that the proposed framework is very effective, if not superior, compared with its counterparts and other algorithms.

In addition to its nutritional value, Paullinia cupana (guarana) is commonly used in traditional medicine, known for its stimulant and medicinal properties. This investigation evaluated the effects of a guarana extract in combination with whole-body vibration (WBV) exercises on Wistar rats. Rats (male, n = 20) were divided into the following four groups: control (CON), treated with guarana (GUA), submitted to 50 Hz of WBV (WBV-E), treated with guarana and submitted to 50 Hz of WBV (GUA + WBV-E), daily for 6-weeks. Guarana altered (p < 0.05) the uptake of the radiopharmaceutical sodium pertechnetate (Na99mTcO4) in muscle. Additionally, it modified the stool consistency, and in combination with WBV decreased the food intake without modifying body mass. The levels of calcium increased in the groups submitted to WBV exercises (WBV-E and GUA + WBV-E) as compared with the GUA group. The outcomes provide additional evidence of the biological effects of guarana separately or in combination with WBV and supports the use of guarana as a functional food.

The present study investigated the effects of forced swimming on the technetium-99m (99mTc) labeling of blood constituents (BloCs). Rats (Wistar) were submitted to forced swim. In previous experiments, swimming animals would recover for different periods of time. Animals not submitted to swimming were used as control. Blood samples were obtained and the 99mTc labeling of BloCs was carried out. Blood cells (BCs), plasma (P), insoluble fractions (IF-P and IF-BCs), and soluble fractions (SF-P and SF-BC) were isolated. Radioactivity was determined, and the percentage of 99mTc incorporated (%ATI) was calculated in each fraction. Results showed that forced swimming decreased the percentage of 99mTc incorporated (%ATI) in IF-P (p < 0.05). It is suggested that the 99mTc labeling of BloCs could be used to verify the effects of the stress conditions on BloCs and that the radionuclide fixation on plasma proteins might be altered in rats submitted to acute stress induced by forced swimming, returning to control levels after recovery.

5-Alkyl-6-(substituted benzyl)-2-thiouracils 3a,c were reacted with (2-chloroethyl) diethylamine hydrochloride to afford the corresponding 2-(2-diethylamino)ethylthiopyrimidin- 4(3H)-ones 4a,b. Reaction of 3a–c with N-(2-chloroethyl)pyrrolidine hydrochloride and/or N-(2-chloroethyl)piperidine hydrochloride gave the corresponding 2-[2-(pyrrolidin-1-yl)ethyl]-thiopyrimidin-4(3H)-ones 5a–c and 2-[2-(piperidin-1-yl)ethyl]thiopyrimidin-4(3H)-ones 6a,b, respectively. Treatment of 3a–d with N-(2-chloroethyl)morpholine hydrochloride under the same reaction conditions formed the corresponding 2-[2-(morpholin-4-yl)ethyl]thiopyrimidines 6c–f. On the other hand, 3a,b were reacted with N-(2-bromoethyl)phthalimide and/or N-(3-bromopropyl)phthalimide to furnish the corresponding 2-[2-(N-phthalimido)ethyl]-pyrimidines 7a,b and 2-[3-(N-phthalimido)-propyl]pyrimidines 7c,d, respectively. Compounds 3a–d, 4a,b, 5a–c, 6a–f and 7a–d were screened against Gram-positive bacteria (Staphylococcus aureus ATCC 29213, Bacillus subtilis NRRL 4219 and Bacillus cereus), yeast-like pathogenic fungus (Candida albicans ATCC 10231) and a fungus (Aspergillusniger NRRL 599). The best antibacterial activity was displayed by compounds 3a, 3b, 4a, 5a, 5b, 6d, 6f, 7b and 7d, whereas compounds 4b, 5b, 5c, 6a, 6b and 6f exhibited the best antifungal activity.

6-Chloro-5-ethyl-, n-propyl- and isopropyluracils 5a-c were efficiently prepared from the corresponding 5-alkybarbituric acids 3a-c via treatment with phosphorus oxychloride and N,N-dimethylaniline to yield the corresponding 5-alkyl-2,4,6-trichloro-pyrimidines 4a-c, which were selectively hydrolyzed by heating in 10% aqueous sodium hydroxide for 30 minutes. The reaction of compounds 5a-c with 1-substituted piperazines yielded the corresponding 5-alkyl-6-(4-substituted-1-piperazinyl)uracils 6a-j. The target 8-alkyltetrazolo[1,5-f]pyrimidine-5,7(3H,6H)-diones 7a-c were prepared via the reaction of 5a-c with sodium azide. Compounds 6a-j and 7a-c were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compound 6h displayed potent broad-spectrum antibacterial activity, while compound 6b showed moderate activity against the Gram-positive bacteria. All the tested compounds were practically inactive against Candida albicans.

Three independent molecules comprise the asymmetric unit of the title compound, C23H20ClF3N4S. The conformations of the molecules are similar with the chlorobenzene and CF3-benzene rings almost perpendicular to, and almost co-planar with, the pyrimidinyl ring [range of dihedral angles = 80.36 (13)–88.07 (14) and 11.89 (14)–23.30 (14)°, respectively]; the benzene rings are roughly orthogonal to each other [64.81 (16)–72.16 (15)°]. In the crystal, two of the independent molecules associate via weak N—H...N(cyano) hydrogen bonds and 12-membered {...HNC3N}2 synthons; the third independent molecule self-associates similarly but about a centre of inversion. The sample studied was found to be a non-merohedral twin and the minor twin component refined to 47.16 (7)%.

The imine residue [C=N = 1.268 (3) Å; conformation = E] is twisted [N—N—C—N = 87.8 (2)°] out of the plane (r.m.s. deviation = 0.016 Å) of the central 1,2,4-triazole ring in the title compound, C30H34F2N6S. A small twist also occurs between the imine and terminal benzene rings [N—C—C—C = −169.8 (2)°]. The piperazine ring (chair conformation) occupies a position almost normal to the central plane [N—N—C—N = 87.8 (2)°]. In the crystal, the molecules are consolidated into a three-dimensional architecture via C—H...S, C—H...π and π–π interactions, the latter between centrosymmetrically related difluorobenzene rings [inter-centroid distance = 3.9389 (18) Å].

The molecule of the title compound, C24H32N4OS, is a functionalized 1,3,4-oxadiazole-2-thione with substituted piperazine and adamantanyl substituents attached at the 3- and 5-positions, respectively, of the oxadiazole spacer with an approximately C-shaped conformation. In the crystal, molecules form dimers via C—H...S interaction. The piperazine ring has a chair conformation; the substituents S, methylene C and adamantane C of the essentially planar oxadiazole ring are approximately in the same plane, with distances of −0.046 (2), −0.085 (5) and 0.003 (4) Å, respectively. The dihedral angle between the planes of the phenyl and oxadiazole rings is 31.3 (3)°.

In the title compound, C24H25N3S2, the S-bound benzene rings have orthogonal [dihedral angle = 85.31 (9)°] and splayed [67.92 (11)°] orientations with respect to the pyrimidine ring; the dihedral angle between the benzene rings is 48.18 (12)°. The pentyl group has an extended all-trans conformation and lies to one side of the pyrimidine ring [the Npy—Cpy—Cp—Cp torsion angle = −85.7 (2)°; py = pyrimidine and p = pentyl].

The title molecule, C17H20N2O, is a functionalized hydrazine with benzoyl and adamantyl substituents attached to the two hydrazine N atoms. In the crystal, molecules are linked via N—H...N hydrogen bonds, forming chains propagating along the a-axis direction. There are also C—H...O, C—H...N and C—H...π interactions present within the chains.

In the title 1,2,4-triazine derivative, C17H19N3O3, the heterocyclic ring is planar (r.m.s. deviation = 0.040 Å) and effectively coplanar with the adjacent phenyl ring [dihedral angle = 4.5 (2)°] but almost perpendicular to the (cyclohex-3-en-1-ylmethoxy)methyl residue [N—N—C—O torsion angle = 71.6 (5)°], so that the molecule has an `L' shape. Supramolecular chains along [001] are formed in the crystal via N—H...O hydrogen bonds where the acceptor O atom is the ether O atom. The adjacent carbonyl O atom forms a complementary C—H...O contact resulting in the formation of a seven-membered {...HNCO...HCO} heterosynthon; the second carbonyl O atom forms an intramolecular C—H...O contact. Chains are connected into a supramolecular layer in the ac plane by π–π interactions [ring centroid–centroid distance = 3.488 (3) Å]. The central atom in the –CH2CH2C(H)= residue of the cyclohexene ring is disordered over two sites, with the major component having a site-occupancy factor of 0.51 (2).

In the title compound, C20H21N5O, the conformation about the imine bond [1.289 (3) Å] is E. Overall, the molecule is disk-shaped with the imidazole ring located above the remainder of the molecule and with the dihedral angles of 10.97 (15) and 12.11 (15)°, respectively, between the imidazole ring and the phenyl and methylbenzene rings; the dihedral angle between the aromatic rings is 8.17 (14)°. Within the urea unit, the N—H atoms are anti to each other and one of the N—H atoms forms an intramolecular N—H...N hydrogen bond. Helical supramolecular chains along [001] are formed via N—H...N(imidazole) hydrogen bonds in the crystal structure. These are connected into a three-dimensional architecture by C—H...O(carbonyl) and C—H...π interactions.

In the title compound, C19H17ClN2O3, the conformation about the ethylene bond [1.333 (2) Å] is E. The ten atoms comprising the quinazoline ring are essentially planar (r.m.s. deviation = 0.032 Å) and their mean plane forms a dihedral angle of 13.89 (7)° with the terminal phenyl ring; the molecule has an open conformation as these substituents are directed away from each other. In the crystal, centrosymmetrically related molecules are connected via N—H...O hydrogen bonds between the amide groups, leading to eight-membered {...HNCO}2 synthons. These are consolidated into a three-dimensional architecture by C—H...O, C—H...π and π–π interactions [ring centroid(N2C4)...centroid(C6) distance = 3.5820 (11) Å].

In the title compound, C21H23N5O2, the conformation about the imine bond [1.287 (3) Å] is E. Overall, the molecule has a disk shape, the dihedral angles between the imidazole ring and the methoxyphenyl and methylphenyl rings being 49.42 (13) and 42.62 (13)°, respectively; the dihedral angle between the benzene rings is 20.11 (11)°. In the urea moiety, the N—H atoms are anti to each other and one of these forms an intramolecular N—H...N hydrogen bond. In the crystal, centrosymmetric dimers are formed via N—H...N(imidazole) hydrogen bonds, which are connected into a three-dimensional architecture by C—H...O(carbonyl) and (methylene)C—H...π interactions. The crystal studied was a non-merohedral twin with a minor component of 48.3 (1)%.

In the title compound, C20H20N2O3, the ten atoms comprising the quinazoline ring are essentially planar (r.m.s. deviation = 0.024 Å), and this plane is almost orthogonal to the terminal phenyl ring [dihedral angle = 82.87 (7)°]. The conformation about the ethylene bond [1.335 (2) Å] is E and there is a significant twist between this residue and the adjacent phenyl ring [C—C—C— torsion angle = −48.4 (3)°]. The crystal structure features centrosymmetric dimeric units linked by pairs of N—H...O hydrogen bonds between the amide groups which lead to eight-membered {...HNCO}2 synthons. These are consolidated into a three-dimensional architecture by C—H...O, C—H...π and π–π interactions [centroid–centroid distances = 3.5087 (8) and 3.5645 (9) Å].

In the title molecule, C18H16N2O3, the five-membered ring has an envelope conformation, with the substituted C atom deviating by 0.342 (4) Å from the mean plane P calculated for the remainder of the non-H atoms of the 2,3-dihydro-1H-indene fragment. The mean planes of quinazoline-2,4(1H,3H)-dione fragment and P form a dihedral angle of 59.08 (4)°. In the crystal, pairs of N—H...O hydrogen bonds link molecules into inversion dimers, and weak C—H...O hydrogen bonds and π–π interactions between the benzene rings of the quinazoline ring systems [centroid–centroid distance = 3.538 (3) Å] further consolidate the packing.

The asymmetric unit of the title compound, C19H16N2O3, comprises three independent molecules (A, B and C). The inversion-related molecule of A is virtually superimposable upon the other two molecules. In each molecule, there is a twist in the link between the approximately syn carbonyl and amine groups [the N—C—C—O torsion angles range from 19.73 (19) to −21.2 (2)°]. Each molecule has a bent shape quantified in terms of the dihedral angle between the indole and indole fused-ring systems [range = 45.69 (5)–47.91 (5)°]. In the crystal, the A and B molecules form dimeric aggregates via ten-membered {...HNC2O}2 synthons, while the C molecules self-associate similarly but about a centre of inversion.

In the title compound, C14H21N3S, the 1,2,4-triazole ring is nearly planar, with a maximum deviation of 0.003 (4) Å. In the crystal, molecules are linked into inversion dimers by pairs of N—H...S hydrogen bonds.

In the title compound, C12H17N3O2S, the 4-methyl-2-methylsulfanyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile part of the molecule is almost planar (r.m.s deviation = 0.062 Å). In the crystal, molecules form centrosymmetric dimers via pairs of N—H...O hydrogen bonds.

In the title molecule, C17H21FN2S, the mean planes of the benzene ring and the thiourea fragment form a dihedral angle of 61.93 (9)°. In the crystal, pairs of weak N—H...S interactions link the molecules, forming inversion dimers.

In the title compound, C27H30N4OS, the 3-(adamantan-1-yl)-4-amino-1H-1,2,4-triazole-5(4H)-thione unit and the O atom are each disordered over two sets of sites with refined site-occupancies of 0.7630 (13) and 0.2370 (13). The 1,2,4-triazole ring of the major component forms dihedral angles of 62.61 (17) and 61.93 (16)° with the benzene rings, while that of the minor component makes corresponding angles of 86.3 (4) and 79.1 (4)°. The dihedral angle between the benzene rings is 39.21 (16)°. The molecular structure is stabilized by an intramolecular C—H...N hydrogen bond, which generates an S(6) ring motif. In the crystal, molecules are linked into inversion dimers by pairs of N—H...S hydrogen bonds.

In the title pyrimidine derivative, C24H28N2O3, the uracil unit is essentially planar with an r.m.s. deviation of 0.0054 (1) Å for the eight non-H atoms. The pyrimidine ring is tilted by a dihedral angle of 77.08 (7)° with respect to the aromatic ring of the 3,5-dimethylbenzyl substituent, whereas it is nearly parallel to the benzene ring of the phenethoxymethyl unit, with a dihedral angle of 8.17 (8)°. An intramolecular C—H...O hydrogen bond generates an S(6) ring motif. In the crystal, molecules are linked by a pair of amide–uracil N—H...O hydrogen bonds into an inversion R22(8) dimer. These dimers are stacked along the b axis through π–π interactions with a centroid–centroid distance of 3.9517 (8) Å. Weak C—H...π interactions are also present.

In the title compound, C19H18N2O2, the two indole ring systems are essentially planar [maximum deviation = 0.015 (2) Å in both indole ring systems] and make a dihedral angle of 72.17 (7)° with each other. In the crystal, the molecules are linked into a zigzag chain along the a axis via N—H...O hydrogen bonds.

The asymmetric unit in the title thiourea derivative, C13H19N3S, comprises three independent molecules (A, B and C). The thiourea groups are superimposable for the three molecules, but there are significant conformational differences. Molecules A and B are approximate mirror images of each other, and molecule C has an intermediate conformation. The dihedral angles between the thiourea groups and the phenyl rings are 52.10 (5), 63.29 (5) and 66.46 (6)° in molecules A, B and C, respectively. Each independent molecule self-associates into a supramolecular chain along [100] via N—H...S hydrogen bonds. Molecules of A and B assemble into layers four molecules thick in the ac plane via C—H...S and C—H...π interactions. Molecules of C self-assemble into layers in the ac plane via C—H...S interactions. The layers stack along the b axis with no specific interactions between them.

The title molecule, C18H19N3O3, lies on a mirror plane that bisects the adamantyl group. In the crystal, C—H...O and C—H...N interactions lead to supramolecular chains along [100]. These assemble into layers in the ab plane via π–π interactions [centroid–centroid distance = 3.6548 (7) Å] between the oxadiazole and benzene rings.

The 1,2,4-triazine ring of the title compound, C8H13N3O3, is nearly planar (r.m.s. deviation = 0.019 Å). The imino group is hydrogen-bond donor to the exocyclic O atom at the 5-position of an adjacent molecule, the N—H...O hydrogen bond generating a chain parallel to the b axis.

The 1,2,4-triazine ring in the title compound, C14H15N3O3, is approximately planar (r.m.s. deviation = 0.019 Å); the C atom at the 6-position deviates by 0.026 (2) Å from the mean plane whereas the C atom at the 2-position deviates by 0.166 (4) Å in the opposite direction. The triazine ring is oriented at 8.60 (13)° with respect to the phenyl ring. The imino group is hydrogen-bond donor to the exocyclic O atom at the 3-position of an adjacent molecule, the hydrogen bond generating an inversion dimer.

The pyrimidine ring of the title compound, C25H30N2O3, is approximately planar (r.m.s. deviation = 0.003 Å); the C atom at the 5-position deviates by 0.012 (3) Å from the mean plane and the C atom at the 6-position by 0.038 (3) Å. In the molecule, the pyrimidine ring is oriented at 86.72 (9) and 59.75 (9)° with respect to the two benzene rings, and the two benzene rings are inclined to each other at 58.35 (9)°. In the crystal, the amino group is hydrogen-bond donor to the exocyclic O atom at the 4-position of an adjacent molecule, the hydrogen bond generating an inversion dimer.

The asymmetric unit of the compound, C20H26N2O5·0.5C2H5OH, consists of two tetrahydropyrimidine-2,4-dione molecules and an ethanol molecule. The pyrimidine rings are nearly planar (r.m.s. deviation = 0.006 Å in one molecule and 0.009 Å in the other); the C atom at the 5-position deviates by 0.083 (3) Å [0.064 (3) Å in the second molecule] from the mean plane and the C atom at the 6-position by 0.034 (3) Å [0.082 (3) Å in the second molecule]. In each molecule, the benzene ring is nearly perpendicular to the pyrimidine ring, the dihedral angle is 88.51 (8)° in one molecule and 84.70 (8)° in the other. The amino group of each tetrahydropyrimidine-2,4-dione molecule is a hydrogen-bond donor to the exocyclic O atom at the 2-position of an adjacent molecule, the hydrogen bond generating an inversion dimer in each case. The ethanol molecule forms a hydrogen bond to the methoxy O atom of one of two independent molecules.

The pyrimidine ring in the title compound, C19H24N2O3, is nearly planar (r.m.s. deviation = 0.008 Å); the C atom at the 5-position deviates by 0.054 (3) Å from the mean plane and the C atom at the 6-position by 0.006 (3) Å in the opposite direction. The benzene ring is approximately perpendicular to the pyrimidine ring [dihedral angle = 83.90 (10)°]. The amino group is hydrogen-bond donor to the exocyclic O atom at the 2-position of an adjacent molecule, the hydrogen bond generating an inversion dimer. The cyclopropyl ring is disordered over two sets of sites with the major component having 71.5 (4)% occupancy.

The six-membered ring of the uracil part of the title compound, C24H28N2O4, is nearly planar (r.m.s. deviation = 0.013 Å); the aromatic ring of the 3,5-dimethylbenzyl substitutent is aligned at 85.4 (1)° with respect to this mean plane. The phenyl ring of the substituent at the 1-position takes up two orientations in a 1:1 ratio. In the crystal, two molecules are liked by a pair of N—H...O hydrogen bonds, generating a centrosymmetric hydrogen-bonded dimer.