The ability to predict macroscopic properties using a compound's chemical structure is an essential idea for chemistry as well as other disciplines such as biology. In this study we investigate how different levels of interventions impact the components of students’ explanations (claims, evidence, and reasoning) of structure–property relationships, particularly related to boiling point trends. These interventions, aligned with Three-Dimensional Learning (3DL), were investigated with four different cohorts of students: Cohort 1 – a control group of students enrolled in an active learning general chemistry course; Cohort 2 – students enrolled in the same active learning general chemistry course but given Intervention 1 (a 3DL worksheet administered during class time); Cohort 3 – students enrolled in the same active learning general chemistry course but given Intervention 1 and Intervention 2 (a 3DL course exam question administered after instruction); and Cohort 4 – a reference group of students enrolled in a transformed active learning general chemistry curriculum in which 3DL is an essential feature and includes Intervention 1 and Intervention 2 as part of the curriculum. We found that Cohort 2 students (with the 3DL worksheet intervention) were more likely than the control group (Cohort 1) to correctly predict the compound with a higher boiling point as well as incorporate ideas of strength of intermolecular forces into their explanations of boiling point differences. When a 3DL exam question was given as a follow up to the 3DL worksheet, students in Cohort 3 were more likely than Cohorts 1 and 2 to correctly identify the claim. Further comparison showed that Cohort 4 (transformed general chemistry curriculum) were more likely than Cohorts 1–3 to also include the ideas of energy needed to overcome stronger forces for a more sophisticated explanation (50% of Cohort 4 students compared to 17–33% for Cohorts 1–3). In addition, 80% of Cohort 4 students were able to construct a correct representation of hydrogen bonding as a non-covalent interaction compared to 13–57% for the other three cohorts.